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Objective To investigate the role of dynamin-related protein 1(Drp-1)and peroxisome proliferator-activated receptor γ coactivator 1-α(PGC-1α)in the lung tissues of neonatal rats with meconium aspiration syndrome(MAS)and its mechanism.Methods Fifty 2-3-week-old SD neonatal rats were randomly divided into five groups(n=10):control group,model group and SN50 low,medium and high concentration groups.In control group,2 ml/kg of saline was injected into the trachea after tracheal exposure,and 2 ml/kg of meconium suspension was injected into the trachea of the rest of groups;after 24 h,control and model groups were left untreated,and 100 μl of each of SN50 concentrations of 10,30,and 60 μg/ml was injected into SN50 low,medium,and high concentration groups intraperitoneally;the rats of each group were killed after 6 h,and the chest X-rays,the gross views of the lungs,the lung wet/dry weight ratios(W/D),and the lungs of the rats in control group and model group were examined.After 6 h,the rats in each group were executed,and the pathological changes of lung tissue were observed by chest radiographs,lung gross view,lung wet/dry weight ratio(W/D)and HE staining;Western blotting was used to detect the changes of nuclear factor κB(NF-κB)(p65),p-NF-κB p65(p-p65),Drp-1,and PGC-1α proteins expression in neonatal rat lung tissues,and immuno-histochemistry was used to observe the expression of p65,Drp-1,and PGC-1α related proteins expression in neonatal rat lung tissues.Results Compared with control group,model group showed inflammatory infiltration in the chest radiograph and gross view,and the W/D and lung injury pathology scores were significantly higher(P＜0.05);compared with model group,the chest radiograph and gross view of inflammation were slightly reduced in SN50 low,medium and high concentration groups,and the W/D and lung injury pathology scores were significantly lower(P＜0.05).Western blotting showed that,compared with control group,the protein expression levels of p-p65 and Drp-1 in the lung tissues of neonatal rats were significantly higher in model group(P＜0.05),and the protein expression level of PGC-1α was significantly lower(P＜0.05);compared with model group,the protein expression levels of p-p65 and Drp-1 were significantly lower in SN50 low,medium,and high concentration groups(P＜0.05),and the difference in the protein expression level of PGC-1α in SN50 low concentration group was not statistically significant(P＞0.05),whereas the PGC-1α expression levels in SN50 medium and high concentration groups were significantly higher(P＜0.05);the difference in the total p65 protein expression levels in each group was not statistically significant(P＞0.05).Immunohistochemical assay results showed that,compared with control group,p65 and Drp-1 protein expression levels were significantly higher in model group(P＜0.05),and PGC-1α protein expression level was significantly lower(P＜0.05);compared with model group,p65 protein expression level was significantly lower in SN50 low concentration group(P＜0.05),and the difference in Drp-1 and PGC-1α protein expression levels were not statistically significant(P＞0.05),Drp-1 protein expression level was significantly lower(P＜0.05),and PGC-1α protein expression level was significantly higher(P＜0.05)in SN50 middle and high concentration groups.Conclusion Fecal inhalation can induce lung tissue inflammation in neonatal rats,and the mechanism may be related to enhanced oxidative stress,promotion of mitochondrial dysfunction,activation of the Drp-1/NF-κB signaling pathway,and inhibition of PGC-1α protein expression.
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Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.
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Objective:To investigate the effect of mitochondrial division of GABAergic neurons in substantia nigra pars reticulata(SNr)on motor dysfunction in mice with acute hepatic encephalopathy(AHE).Methods:AHE mice model was established by intraperitoneal injection of thioacetamide(TAA).The changes of liver lobules in AHE mice were observed by hematoxylin-eosin(HE)staining.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)and blood ammonia in AHE mice were detected by biochemical detection kit.Then,the motor function of AHE mice was observed by rod fatigue test,elevated cross maze test and open field test.Furthermore,the changes of mitochondrial area,perimeter,roundness and other morphological indicators in SNr of AHE mice were ob-served and analyzed by transmission electron microscopy.The expression of mitochondrial division and fusion related molecules in SNr of AHE mice was observed by Western Blot.Then,the expression of mitochondrial dynamic related protein 1(DRP1)in SNr of AHE mice was targeted by AAV virus.The mitochondrial membrane potential(MMP),ATP and reactive oxygen species(ROS)in SNr were detected by fluorescence enzyme marker,and the changes of motor function of mice were observed.Results:Compared with the control group,the motor function of AHE mice was signifi-cantly decreased,the mitochondrial division of SNr was significantly enhanced,and the expression of mitochondrial divi-sion related proteins was significantly increased.The MMP in SNr of AHE mice was significantly decreased,the ATP of cells was decreased,and the ROS was increased.After targeted inhibition of DRP1 expression in SNr of AHE mice,the movement was improved;further observation found that after the mitochondrial division in SNr of AHE mice was inhibi-ted,the MMP was significantly increased,the ATP of cells was increased,and the ROS was decreased,which demon-strated that the mitochondrial function was significantly improved.Conclusion:Targeted inhibition of mitochondrial di-vision of GABAergic neurons in SNr of AHE mice can improve mitochondrial morphology and function,thus alleviating their movement disorders.
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Objective:To explore the mechanism of Mito-TEMPO inhibiting the activation of BV2 microglia induced by lead(Pb)exposure.Methods:Mouse microglia BV2 were cultured in vitro.The effects of different concentrations of lead exposure on the viability of BV2 cells were determined by MTT colorimetric method,and a model of lead expo-sure was developed and intervened with Mito-TEMPO antioxidant.Immunofluorescence staining was used to detect the expression of M1 activation marker CD86 protein.Enzyme-linked immunosorbent assay was used to detect the expression of pro-inflammatory factors interleukin-1 β(IL-1β),tumor necrosis factor α(TNF-α),interleukin-6(IL-6).Mito-chondrial superoxide indicator(MitoSOX)staining was used to detect the level of mitochondrial oxidative stress.JC-1 staining was used to detect mitochondrial membrane potential.The respiratory ability of mitochondria was detected by cell energy metabolism analysis system(O2k).Results:Compared with the control group,the expression of CD86 protein,the levels of pro-inflammatory cytokines IL-1β,TNF-α and IL-6 in BV2 cells increased significantly,the level of oxidative stress in mitochondria increased significantly,and the mitochondrial membrane potential and respiratory ability decreased significantly in lead exposed group.Mito-TEMPO treatment significantly reduced the oxidative stress and functional damage of mitochondria in BV2 cells,and significantly inhibited the M1 activation level of BV2 cells.Conclusion:The results show that Mito-TEMPO treatment can reverse the M1 activation of BV2 cells induced by lead exposure,and the specific mechanism may be related to the reduction of mitochondrial oxidative stress and dysfunction by Mito-TEMPO.
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Objective To explore the efficacy of a new anti-heart failure drug,Entresto,in the prevention of cardiotoxicity caused by doxorubicin(DOX).Methods Male adult ICR mice were randomly divided into three groups(n = 8):control group,DOX group and DOX plus Entresto group.Cardiac function of mice was measured by echocardiography.H9c2 cells were pretreated with Entresto(0-48 μmol/L)for 24 hours in the presence or absence of DOX(1 mmol/L),and then cell viability,oxidative stress,apoptosis and mitochondrial function were evaluated.Results As compared with the control group,leakage of CK,CK-MB and LDH increased significantly in the DOX group(P<0.01),and left ventricular systolic dysfunction occurred.Entresto administration reversed these changes in the DOX group.The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group(P<0.05).As compared with the DOX group,the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group(P<0.05),and mitochondrial membrane potential increased significantly(P<0.05).Entresto reversed the inhibitory effect of DOX on SIRT1/PGC-1α/MFN2 signaling pathway.Conclusions Entresto improves DOX-induced cardiotoxicity by inhibiting ROS-mediated oxidative stress and apoptosis,and its mechanism may be related to SIRT1/PGC-1α/MFN2 signal transduction pathway.
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Objective To explore the role of protective function of Sestrin2(Sesn2)to mitochondria in alleviating cognitive dysfunction in mice with sepsis-associated encephalopathy(SAE).Methods 6-week-old male C57BL/6J mice were randomly divided into three groups:sham group,CLP group and CLP plus eupatilin group,40 mice in each group.A sepsis model was induced by cecal ligation and perforation(CLP).The CLP plus eupatilin group was treated with eupatilin.Neurobehavioral test and Morris water maze(MWM)were used to deter-mine neurobehavior and spatial learning and memory function in mice.The number of neurons in hippocampal CA1 area was counted by Nissl staining.HT22 cells were randomly divided into a control group(Con),lipopolysaccha-ride group(LPS),LPS plus eupatilin treatment group(LPS plus eupatilin)and LPS plus eupatilin and Nrf2 siRNA treatment group(LPS plus eupatilin and si-Nrf2).Apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)staining,Mitochondrial membrane potential(MMP)was used to analyze mitochondrial damage.Results Seven days after CLP,as compared with sham mice,Sesn2 in hippocampus and cortex decreased significantly in CLP mice(P<0.01).As compared with CLP group,the survival rate in CLP plus eupatilin group increased significantly(P<0.05).As compared with sham group,the mice in CLP group showed a relatively high nerve injury score(P<0.05),and had fewer platform crossings and shorter target stay time,while the mice in CLP plus eupatilin group exhibited a lower injury score(P<0.05),and stayed in the target area for a longer time(P<0.05).As compared with sham group,the co-localization rate of neurons,Sesn2 and Nrf2 in CLP group decreased significantly(P<0.05),and the number of CD68/Iba-1 positive microglia increased significantly(P<0.05),while CLP plus eupatilin group reversed these changes.As compared with Con group,apoptosis and MMP level in LPS group increased significantly(P<0.01),while apoptosis and MMP level in LPS plus eupatilin group were lower than those in LPS group(P<0.05).However,Nrf2 knockdown(LPS plus eupatilin and si-Nrf2 group)reversed the anti-apoptosis and mitochondrial protection of eupatilin.Conclusions Eupatilin can alleviate cognitive dysfunction and neurological deficit in SAE mice by activating Sesn2-Nrf2 pathway,and improve inflammatory microenvironment by alleviating mitochondrial dysfunction.
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BACKGROUND:The aging of mesenchymal stem cells is one of the main causes of aging-related diseases,and seriously affects its clinical application.Traditional Chinese medicine has a good anti-aging effect,and it can inhibit the aging of mesenchymal stem cells to promote its application in tissue engineering and prevent and treat aging-related diseases. OBJECTIVE:To review the effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells. METHODS:We searched CNKI and PubMed for the literature on inhibiting mesenchymal stem cell aging with traditional Chinese medicine from 2012 to 2022.The keywords were"traditional Chinese medicine,mesenchymal stem cells(MSCs),aging"in Chinese and English,respectively.Finally,92 articles were included for further review. RESULTS AND CONCLUSION:(1)We summarized five main mechanisms of the aging of mesenchymal stem cells:DNA damage,telomere shortening,oxidative stress,autophagy disorder and mitochondrial dysfunction.(2)This paper reviewed the phenotypic characteristics of senescent mesenchymal stem cells,including increases in cell volume,decreases in proliferation and multi-directional differentiation,increases in β-galactosidase activity,and activation of p21 and p16 pathways,and so on.(3)We summarized the main mechanisms of Chinese medicine inhibiting the senescence of mesenchymal stem cells at present,including inhibiting the activation of the Wnt pathway,inhibiting the production of mitochondrial reactive oxygen species,promoting the silencing of information regulator factor 2 homolog 1,phosphatidylinositol 3-kinase/protein kinase B,adenosine 5'-monophosphate-activated protein kinase and nuclear factor E2 related factor 2 pathway activation,and promoting the expression of telomerase reverse transcriptase.(4)At present,bone marrow mesenchymal stem cells are the most widely studied in the research of traditional Chinese medicine to inhibit the aging of bone marrow mesenchymal stem cells,and the effect is better.(5)Zuogui Wan,Bushen Tiaogan Formula,resveratrol,Astragalus membranaceus and other traditional Chinese medicines can prevent and treat osteoporosis by promoting the proliferation and osteogenic differentiation of aging mesenchymal stem cells.However,the mechanism of Chinese medicine in improving the paracrine function of mesenchymal stem cells and preventing other aging-related diseases by inhibiting the aging of mesenchymal stem cells needs to be further explored.
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BACKGROUND:Connexin 43(Cx43),which is thought to be engaged in the gap junction process and build the structural groundwork for the development of direct material signaling channels between cells,is crucial for maintaining the homeostatic balance of tissue metabolism.Recent research,however,has revealed fresh information about its distinct hemichannel function and highlighted the significance of its subcellular localization and self-fragmentation for cellular physiological activities and pathological processes. OBJECTIVE:To systematically summarize the molecular characteristics and expression of Cx43 in a variety of cells,concentrate on the pathological and physiological roles of channel-dependent Cx43 and channel-independent Cx43,and investigate the potential value in disease treatment by reviewing the pertinent literature in the database. METHODS:The Chinese and English keywords were"gap junction,connexin 43(Cx43),hemichannel,channel-dependent Cx43,channel-independent Cx43,extracellular vesicles(EVs),mitochondria,GJA1-20k",which were searched in PubMed and CNKI.Finally,81 articles were selected for review. RESULTS AND CONCLUSION:(1)The canonical role of Cx43 is to form a gap junction channel.Channel-dependent Cx43 has primarily involved in disease physiopathological processes by directly constituting gap junction channels,but full attention should be paid to the issue of its structural and functional integrity.Adhesion is a crucial characteristic of gap junctions,which are strongly associated with barrier-like diseases.(2)The non-canonical role of Cx43 is non-gap junction channel-dependent effect.In addition to being localized at the plasma membrane,inner mitochondrial membrane,extracellular vesicle surface,and other structures,Cx43 hexamer has also been found to play a role in positive pro-inflammatory mechanisms,mitochondrial functional metabolism,and targeted uptake of extracellular vesicles in inflammatory diseases.Selective shortened segments control mitochondrial homeostasis by encouraging the polymerization of peri-mitochondrial actin and are involved in the targeted translocation of full-length Cx43 to intracellular structural domains.(3)The development of targeted medicines and the solving of issues like the mechanism of seed cell transformation in tissue engineering-based therapies are both made possible by these two categories of impacts.The interactions of various types of Cx43,however,are frequently not fully taken into account in some of the existing original studies,which confuses the overall characteristics and skews the results.(4)It is necessary to systematically frame the physiological characteristics of Cx43 in different forms and its potential mechanisms in various diseases,so as to provide a reference for the exploration of the Cx43 integrity mechanism and the diagnosis and treatment of multiple diseases.
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BACKGROUND:Clinical studies have found good analgesic effects of silver needle-thermal conduction therapy in patients with myofascial pain syndrome,but the exact mechanism remains unclear. OBJECTIVE:To observe the effect of silver needle-thermal conduction therapy on silent information regulator homolog 3(SIRT3)changes and mitochondrial ultrastructure in a rat model of myofascial pain syndrome. METHODS:Twenty rats were randomly selected from 26 Sprague-Dawley rats and were subjected to percussion combined with motor fatigue for replicating the rat model of myofascial pain syndrome.Sixteen rats that were successfully modeled were randomly divided into model group and silver needle-thermal conduction therapy group(treatment group),with eight rats in each group.The remaining rats were used as controls(normal group).The treatment group was treated with silver needle-thermal conduction therapy.Mechanical withdrawal threshold and thermal withdrawal latency of rats were measured at 1 day before modeling,1 day after modeling and 14 days after treatment.Electromyographic activities of the right medial femoral muscle were measured at 14 days after treatment.The right medial femoral muscle tissue was taken for hematoxylin-eosin staining to observe the local morphology and for transmission electron microscopy to observe the mitochondrial ultrastructure.Western blot assay was performed to detect SIRT3 expression. RESULTS AND CONCLUSION:Pain threshold:The mechanical withdrawal threshold and thermal withdrawal latency of the model and treatment groups were significantly decreased compared with those in the normal group and before modeling(P＜0.01).After treatment,the mechanical withdrawal threshold and thermal withdrawal latency of rats were significantly higher in the treatment group compared with the model group(P＜0.01).Electromyography:The rats in the model group showed spontaneous electrical activity in the right medial femur,while the rats in the treatment group showed reduced spontaneous electrical activity,longer time frame(P＜0.01)and lower wave amplitude(P＜0.05)compared with the model group.Hematoxylin-eosin staining:In the normal group,rat muscle fibers arranged closely and regularly.In the model group,the muscle fibers of rats were atrophied,degenerated,and disordered in arrangement.In the treatment group,rat muscle structure disorder improved.Mitochondrial microstructure:Under the transmission electron microscope,mitochondrial structure in the normal group was normal;mitochondrial swelling with broken or disappeared cristae appeared in the model group;mitochondrial swelling in the treatment group was obviously relieved or tended to be normal.SIRT3 expression:SIRT3 expression was significantly downregulated in the model group compared with the normal group,but was significantly upregulated in the treatment group compared with the model group(P＜0.05).To conclude,abnormalities in local muscle mitochondria and downregulation of SIRT3 expression suggest the presence of impaired energy metabolism in the rat model of myofascial pain syndrome.Mitochondrial changes recover and are close to normal after the silver needle-thermal conduction therapy,and the expression of SIRT3 is also upregulated close to the normal group,indicating the silver needle-thermal conduction therapy may play a therapeutic role by promoting mitochondrial repair and improving energy metabolism disorder.
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BACKGROUND:Mitochondrial reactive oxygen bursts have been shown to play a key role in skeletal muscle ischemia-reperfusion injury.3-Nitro-N-methylsalicylamide(3-NNMS)can effectively reduce the electron transport rate and has a potential protective effect on limb ischemia-reperfusion injury,but there is no clear research and clinical application. OBJECTIVE:To investigate the protective effect of 3-NNMS on the skeletal muscle after limb ischemia-reperfusion injury in rats and its mechanism. METHODS:Forty healthy 8-week-old Sprague-Dawley rats were randomly divided into control group,0,25 and 125 μg/mL 3-NNMS groups,with 10 rats in each group.Animal models of limb ischemia-reperfusion injury were prepared in the latter three groups.3-NNMS was injected into the injury site 30 minutes before reperfusion.The animals were sacrificed 2 hours after reperfusion.Blood from the apical part of the heart,and the tissue of the rectus femoris muscle of the right lower limb were taken for testing.The pathological morphology of the rectus femoris muscle was detected by hematoxylin-eosin staining.Serum levels of creatine kinase found in the skeletal muscle(CK-MM),lactate dehydrogenase,and myeloperoxidase were detected using ELISA;the levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde,reactive oxygen species,superoxide dismutase,catalase and glutathione peroxidase in the rectus femoris muscle were measured;and adenosine triphosphate(ATP)level,ATPase activity,and mitochondrial respiratory control rate were tested. RESULTS AND CONCLUSION:Compared with the control group,the model rats with ischemia-reperfusion injury had increased serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase,increased levels of nuclear factor κB,tumor necrosis factor α,interleukin 1β,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,decreased levels of catalase and glutathione peroxidase in the rectus femoris muscle,and reduced ATPase activity and mitochondrial respiratory control rate.Moreover,cell morphology was irregular,inflammatory cell infiltration was obvious,and the cells were swollen in rats after ischemia-reperfusion injury.Compared with the 0 μg/mL group,the serum CK-MM and lactate dehydrogenase levels decreased,the levels of nuclear factor κB and cyclooxygenase 2 in the rectus femoris muscle decreased,reactive oxygen species level decreased,and superoxide dismutase activity increased in the 25 μg/mL group;cell morphology was more regular,inflammatory cell infiltration was lighter,and cell swelling was alleviated.Compared with the 0 μg/mL group,the 125 μg/mL group had a reduction in the serum levels of CK-MM,lactate dehydrogenase,and myeloperoxidase and the levels of nuclear factor κB,tumor necrosis factor α,cyclooxygenase 2,malondialdehyde and reactive oxygen species in the rectus femoris muscle,as well as an increase in the levels of superoxide dismutase and glutathione peroxidase in the rectus femoris muscle,and mitochondrial respiratory control rate.Moreover,the cells were arranged neatly,the outline was clear and complete,and the inflammatory cell infiltration was light.To conclude,3-NNMS can alleviate the functional impairment of the skeletal muscle caused by limb ischemia-reperfusion,and its mechanism of action may be through improving mitochondrial function,reducing reactive oxygen species production,decreasing oxidative stress and inflammatory response,and thus reducing tissue damage and repairing skeletal muscle function.
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BACKGROUND:Parkinson's disease is a neurodegenerative disease,and its pathogenesis involves mitochondrial dysfunction.Exercise has a potential ameliorative effect on mitochondrial dysfunction related to Parkinson's disease,but there is no comprehensive review and in-depth analysis in this field. OBJECTIVE:To comprehensively review and analyze mitochondrial dysfunction related to Parkinson's disease and the potential ameliorative effect of exercise,thereby providing new ideas and methods for the treatment and prevention of Parkinson's disease. METHODS:We searched the Web of Science,PubMed,CNKI,WanFang,and VIP databases with the keywords of"mitochondria,mitochondrial function,mitochondrial disease,mitochondrial dysfunction,Parkinson's disease,Parkinson,exercise,physical activity,exercise training,exercise therapy,mitochondrial impairment,mitochondrial damage,mitochondrial defects"in Chinese and"mitochondria,Parkinson's disease,Parkinson disease,physical exercise,exercise,physical activity,mitochondrial dysfunction,mitochondrial damage,mitochondrial impairment,athletic training,exercise training,rehabilitation"in English.A total of 89 articles were included for review and analysis. RESLUTS AND CONCLUSION:Parkinson's disease is closely related to mitochondrial dysfunction,including mitochondrial biogenesis inhibition,reduced autophagy,increased apoptosis,abnormal elevation of Ca2+ concentration,and increased oxidative stress in Parkinson's disease patients.Exercise has a positive effect on mitochondrial dysfunction related to Parkinson's disease,by promoting mitochondrial biogenesisand autophagy,regulating mitochondrial morphology,altering the plasticity of the mitochondrial respiratory chain,and reducing oxidative stress,thus helping to improve the development and progression of Parkinson's disease.However,the detailed mechanism between mitochondrial dysfunction and the ameliorative effect of exercise is still not fully understood,and future clinical studies can be conducted to validate the results of animal models and gain insights into the benefits and mechanisms of exercise in patients with Parkinson's disease.
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Objective To analyze the distribution characteristics of traditional Chinese medicine(TCM)syndrome types in patients with osteoporosis and the distribution differences of clinical and serological indicators in TCM syndrome types.Meth-ods A total of 69 patients with osteoporosis were collected from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine and Qifu Hospital Affiliated to Jinan University.The general information,bone mineral density T value,fasting periph-eral venous blood in the morning were collected.The expression of telomerase protective factor 1(POT1),telomerase reverse transcriptase(TERT),serum 8-hydroxy-2'-deoxyguanosine(8-OHdG)and superoxide dismutase 2(SOD2)were detected by ELISA.Finally,the above data were statistically analyzed.Results There were significant differences in body weight,height,bone mineral density,POT1,TERT,and 8-OHdG among the four syndromes(P＜0.05).In terms of correlation,the relation-ship between bone mineral density and each parameter in different syndrome types was explored.The bone mineral density of qi stagnation and blood stasis syndrome was positively correlated with SOD2 value.There is a positive correlation between bone min-eral density and 8-OHdG in patients with Yin deficiency of liver and kidney.TERT was positively correlated with qi stagnation and blood stasis syndrome.Liver and kidney Yin deficiency syndrome was positively correlated with weight and bone mineral den-sity,and negatively correlated with TERT value.Weight was negatively correlated with qi and blood stasis syndrome.Conclusion In TCM syndrome differentiation of osteoporosis,there were statistical differences in weight,height,bone mineral density,ser-um POT1,TERT and 8-OHdG among Qi-stagnation and blood stasis,spleen-kidney Yang deficiency,liver-kidney Yin deficiency and Qi-blood-peace syndrome.In different syndrome types,serum SOD2 and 8-OHdG were the influencing factors of bone miner-al density.Serum TERT and 8-OHdG are the main factors affecting the dialectical classification of osteoporosis.
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Diabetic cardiomyopathy(DCM)is a complication of diabetes mellitus.It is characterized by abnormal myocardial cells leading to diastolic and systolic dysfunction,which can eventually lead to heart failure,impair the health of diabetic patients and worsen the poor prognosis.Studies indicated that mitochondrion directly participated in occurrence and development of DCM,involving glucose and lipid metabolic regulation,calcium homeostasis main-tenance,reactive oxygen species(ROS)level and oxidative stress etc.,whose normal functioning is necessary for human health.Mitochondrial dysfunction is closely associated with occurrence and development of DCM.The pres-ent article makes a review on mitochondrial structure and physiological function,dynamics and dysfunction,and role of mitochondrial dysfunction in DCM,and explore new targets for the prevention and treatment of DCM.
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Dry age-related macular degeneration(AMD)is a degenerative disease affecting the macular region of the retina,and aging changes in retinal and choroidal tissues are an important factor in AMD pathogenesis.Cell aging is an irre-versible state of cell cycle arrest triggered by certain physiological processes or stressful injury,affecting a variety of physi-ological and pathological processes.An increasing number of studies have shown that cell aging plays an essential role in the occurrence and development of AMD.This paper reviews the mechanisms of cell aging and its relationship with dry AMD,aiming to provide new ideas for the treatment of dry AMD.
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Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P＜0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P＜0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.
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Objective To observe the effects of Bushen Zhuyun Prescription on regulating mitochondrial function and endometrial angiogenesis;To explore its mechanism of improving endometrial receptivity.Methods The mouse model of controlled ovarian hyperstimulation(COH)was established,and the mice were randomly divided into normal group,model group,and Bushen group,with 20 mice in each group.Bushen group received Bushen Zhuyun Prescription for gavage for 11 d,and the normal group and model group received normal saline for gavage.The number of embryo implantation was counted,the endometrial morphology was observed by HE staining,α-smooth muscle actin(α-SMA)expression was observed by immunofluorescence staining.Human endometrial microvascular endothelial cells(HEMECs)were cultured in vitro,they were divided into control group,VEGFA group,Bushen group and VEGFA + Bushen group,and were intervened with VEGFA and/or Bushen Zhuyun Prescription medicated serum.The activities of mitochondrial respiratory chain complexes Ⅰ-Ⅳ,the content of ATP,the expression of PCNA and Caspase-3 were detected.Results Animal experiment showed that,compared with the normal group,the number of embryo implantation in model group significantly decreased(P<0.05),α-SMA protein expression in endometrial tissue significantly decreased(P<0.05);compared with the model group,the number of embryo implantation in Bushen group significantly increased(P<0.05),α-SMA protein expression in endometrial tissue significantly increased(P<0.05).Cell experiment showed that,Bushen Zhuyun Prescription medicated serum could increase the activity of mitochondrial respiratory chain complexes Ⅰ-Ⅳ and ATP content in HEMECs,promote PCNA protein expression,and inhibit Caspase-3 protein expression(P<0.05,P<0.01).Conclusion Bushen Zhuyun Prescription can promote endometrial angiogenesis through improving mitochondrial function.
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Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.
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Objective:To evaluate the effect of esketamine on cerebral ischemia-reperfusion (I/R) injury and the association with mitochondrial stress in mice.Methods:The experiment was performed in two parts. Part Ⅰ Eighteen SPF male C57BL/6 mice, aged 8-12 weeks, with body mass index of 28-30 g, were divided into 3 groups ( n=6 each) by a random number table method: sham operation group (S group), cerebral I/R group (IR group), and esketamine plus cerebral I/R group (E+ IR group). Cerebral I/R was produced by occlusion of middle cerebral artery for 1 h followed by 24-h reperfusion in anesthetized mice.Esketamine 10 mg/kg was intraperitoneally injected at 20 min before developing the model in E group. Neurological function was evaluated using the Zea Longa score and balance beam test (Feeney score). The cerebral infarct size was determined by TTC staining. Part Ⅱ Primary cortical neurons were isolated and cultured and then divided into 3 groups ( n=42 each) using a random number table method: control group (group C), oxygen-glucose deprivation-reoxygenation (OGD/R) group, and esketamine plus OGD/R group (group E+ OGD/R). Cells were subjected to O 2-glucose deprivation for 1 h followed by restoration of O 2-glucose supply for 24 h. The cells were treated with 25 μmol/L esketamine for 40 min before preparing the model in E+ OGD/R group. The neuronal viability was measured by the CCK-8 assay. The ultrastructure of neurons was observed with a transmission electron microscope. The levels of reactive oxygen species (ROS), glutathione peroxidase (GSH-px) and malondialdehyde (MDA) were determined, and the mitochondrial membrane potential was determined by JC-1 kit. The neuronal apoptosis was detected by TUNEL staining, and the apoptosis rate of neurons was calculated. The expression of Bax, cytochrome C (CytC), cleaved-caspase-9, caspase-3 and cleaved-caspase-3 was detected by Western blot. Results:Part Ⅰ Compared with S group, the Zea Longa score, Feeney score and cerebral infarct size were significantly increased in IR group ( P<0.01). Compared with IR group, the Zea Longa score, Feeney score and cerebral infarct size were significantly decreased in E+ IR group ( P<0.01). Part Ⅱ Compared with C group, the cell viability and activity of GSH-px were significantly decreased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were increased, and the expression of Bax, Cyt C and cleaved-caspase-9 was up-regulated in OGD/R group ( P<0.01). Compared with OGD/R group, the cell viability and activity of GSH-px were significantly increased, the apoptosis rate of neurons, levels of ROS and MDA, mitochondrial membrane potential, and cleaved-caspase-3/caspase-3 ratio were decreased, and the expression of Bax, Cyt C and cleaved-caspase-9 was down-regulated in E+ OGD/R group ( P<0.01). Conclusions:Esketamine can alleviate cerebral I/R injury in mice, and the mechanism may be related to inhibition of mitochondrial stress in neurons, improvement in mitochondrial function, and inhibition of mitochondria-dependent apoptosis in neurons.
摘要
AIM To explore the effects of Buyang Huanwu Decoction on mitochondrial oxidative damage and PKCε-Nampt pathway in rats following cerebral ischemia reperfusion(I/R).METHODS The rats were randomly divided into the sham operation group,the model group,Buyang Huanwu Decoction group(14.3 g/kg)and edaravone group(3 mg/kg).Except those of the sham operation group,SD rats of other groups were induced into models of brain I/R injury by MCAO method,followed by corresponding drug administration 24 hours after operation.After 7 days of administration,the rats had their neurological deficit evaluated by neurological function scoring;thier expression of neuron marker MAP-2 detected by immunofluorescence staining;their neuron damage observed and the oxidative damage evaluated through assessment of their ROS levels and MDA and SOD activities;their changes of mitochondrial membrane potential detected by fluorescent probe JC-1;their ratio of NAD+/NADH detected using modified enzyme circulation method;their expressions of PKCε,p-PKCε and Nampt proteins detected with Western blot;and their positive expressions of p-PKCε and Nampt proteins detected with immunohistochemistry method.RESULTS Compared with the model group,Buyang Huanwu Decoction group shared decreased cerebral infarction volume and neurological function score(P<0.05);increased cerebral fluorescence intensity of MAP-2(P<0.05);reduced neuronal damage,decreased cerebral levels of ROS and MDA(P<0.05);increased SOD activity,mitochondrial membrane potential and NAD+/NADH ratio(P<0.05);and increased protein expressions of p-PKCε and Nampt(P<0.05).CONCLUSION Buyang Huanwu Decoction can improve mitochondrial function and reduce brain I/R injury in rats by activating their PKCε-Nampt signaling pathway.
摘要
Objective @#To investigate the possible mechanism of metformin (Met) -induced cardiomyocyte autoph- agy in protecting myocardial injury in septic mice．@*Methods @# The model of myocardial injury in septic mice was es- tablished by cecal ligation and puncture ( CLP) ．Sixty Kunming mice were randomly divided into sham operation group (Sham group) ，model group ( CLP group) ，model + dimethyl sulfoxide ( DMSO) group ( CLP + DMSO group) ，model + metformin (Met) group (Met group) ，model + Met + 3-methyladenine (3-MA) group (Met + 3- MA group) ，model + Met + compound C ( CC) group (Met + CC group) ，with 10 mice in each group．The Met， Met + 3-MA and Met + CC groups were intraperitoneally injected with Met (200 mg / kg) once a day for 2 weeks be- fore modeling．The Met + 3-MA group was intraperitoneally injected with 3-MA ( 10 mg / kg) 1 h before surgery. The Met + CC group was intraperitoneally injected with CC (20 mg / kg) 30 min before surgery．The model was es- tablished 24 h after the last injection of Met．The heart and blood of all mice were collected 24 h after surgery．The Western blot technique was employed to assess the relative expression levels of microtubule-associated protein 1 light chain 3 (LC3) isoforms，namely LC3 I and LC3 II，autophagy effector protein 1 (Beclin-1) ，ubiquitin-bind- ing protein 62 (p62) ，B-cell lymphoma / leukemia-2 (Bcl-2) ，Bcl-2-associated X protein (Bax) ，adenosine mono- phosphate (AMP) kinase (AMPK) and phosphorylated AMPK (p-AMPK) ．Myocardial pathological changes were observed by hematoxylin-eosin (HE) staining．The changes of myocardial mitochondria and autophagosomes were observed by electron microscopy．Hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardium． Electron microscopy was used to observe the changes of myocardial mitochondria and autophago- somes. @*Results @# Compared with Sham group，the relative protein expression of Beclin-1，p62，p-AMPK / AMPK and LC3 II / LC3 I in CLP and CLP + DMSO groups had no statistical significance，but Bax increased and Bcl-2 de- creased in CLP group (P＜0. 01) ．Compared with CLP group，the relative expression of Beclin-1 protein and LC3 II / LC3 I in Met group increased and p62 decreased (P＜0. 01) ，Bax decreased and Bcl-2 increased (P＜0. 01) . Compared with Met group，the relative protein expression of Beclin-1 and LC3 II / LC3 I in Met + 3-MA group de- creased and p62 increased (P＜0. 05) ，Bax increased and Bcl-2 decreased (P＜0. 05) ．Besides，the relative pro- tein expression of p-AMPK / AMPK in Met + CC group decreased (P＜0. 05) ．HE staining showed that there was no disorder in myocardial fibers in Sham group，and a large number of inflammatory cells infiltrated the myocardial fibers of CLP group in a clear disorder．The Met group showed vacuolar changes in the myocardium，while the Met + 3-MA group showed disordered arrangement of myocardial fibers and a small amount of inflammatory cell infiltra- tion．Under electron microscopy，the morphology of myocardial mitochondria in the Sham group was normal，while in the CLP group，the arrangement of mitochondrial cristae was disordered with vacuolar changes，and occasional autophagosomes were observed．Mitochondria in Met group showed slight swelling and a large number of autophago- somes．The mitochondria in the Met + 3-MA group showed significant swelling with a small amount of autophago- somes．@*Conclusion @#The protective effect of metformin on myocardial injury in septic mice can reduce cardiomyo- cyte apoptosis and improve mitochondrial damage by activating AMPK signaling pathway to induce autophagy.