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BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo. OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them. METHODS:The first author searched PubMed and Web of Science databases by using"cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells"as English search terms,and searched CNKI and Wanfang databases by using"myocardial patch,biological 3D printing,myocardial"as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis. RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial patches mainly include:making myocardial patches after co-cultivation of multiple cells,improving the ink formulation and scaffold composition in biological 3D printing technology,improving the therapeutic effect of myocardial patches,suppressing immune rejection after transplantation,and perfecting the differentiation and cultivation protocols of stem cells.(4)There is no optimal cell source or method for making myocardial patches,and myocardial patches obtained from a particular cell or technique alone often do not achieve the desired therapeutic effect.Therefore,researchers need to choose the appropriate strategy for making myocardial patches based on the desired therapeutic effect before making them.
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Neonatal necrotizing enterocolitis(NEC)is a life-threatening intestinal disease in newborns, and early identification of NEC is a major clinical challenge.Although clinical manifestations, routine laboratory tests and imaging examinations are essential for NEC, more and more studies in recent years based on the understanding of the pathogenesis of NEC have reported that NEC-related biomarkers such as fatty acid-binding proteins, cytokines, and intestinal flora have potential value in its prediction, early diagnosis, severity assessment and prognosis.This review will discuss the biomarkers related to NEC that have been studied in recent years from three aspects: blood, urine and feces, so as to guide clinical application.
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Objective:To study the risk factors of stage Ⅱ/Ⅲ necrotizing enterocolitis(NEC)in very low birth weight infants by retrospective clinical analysis.Methods:Very low birth weight infants admitted to the NICU of Shanghai Children′s Medical Center within 24 hours after birth from July 1, 2017 to June 30, 2022 were included.Control group and NEC group were determined according to Bell staging criteria.Basic data, maternal history, major adverse events of preterm infants before NEC onset, and treatment during hospitalization were collected.Results:There were 437 cases in control group and 22 cases in NEC group.Compared with the control group, the gestational age of NEC group was lower[28.79(27.86, 29.61)weeks vs 30.00(28.79, 31.71)weeks, P=0.002]. The proportion of sepsis was higher(36.4% vs 6.6%, P<0.05), especially the proportion of late-onset sepsis(36.4% vs 6.2%, P<0.05). The proportion of hemodynamically significant patent ductus arteriosus(hsPDA)was higher(27.3% vs 5.7%, P<0.05). The proportion of shock before NEC onset was higher(18.2% vs 3.4%, P=0.010). The proportion of RBC transfusion within 48 hours before NEC onset was higher(27.3% vs 9.8%, P=0.026). However, the ratio of eclampsia/preeclampsia in pregnant mother was lower(0 vs 24.3%, P=0.008). Conclusion:Small gestational age, sepsis, hsPDA, shock and blood transfusion are risk factors for NEC, while eclampsia/preeclampsia in pregnant mother may be a protective factor for NEC.
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Objective:To develop and validate an early prediction model for moderate and severe periventricular-intraventricular hemorrhage (M/S PIVH) in very/extremely preterm infants (V/EPIs).Methods:From January 1, 2017 to December 31, 2021, preterm infants with gestational age (GA) <32 w admitted to the Neonatal Intensive Care Unit of our hospital within 24 h after birth were enrolled. The infants were assigned into no-or-mild (N/M) PIVH group and M/S PIVH group according to postnatal cranial ultrasound within 2 w after birth. Clinical data including pregnancy and perinatal history, complete blood counts (CBC) and blood gas analysis (BGA) within 24 h after birth were retrospectively collected. The univariate analysis, stepwise regression analysis and multivariate logistic regression analysis were used to determine possible predictive risk factors and to establish an early prediction model. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model. The Hosmer-Lemesshow test was introduced to make calibrations of the model. Bootstrap method was used for internal validation.Results:Among 512 preterm infants, 460 (89.8%) were in N/M PIVH group and 52 (10.2%) in M/S PIVH group. Cesarean section ( OR=0.323, 95% CI 0.155-0.669, P<0.001), GA ( OR=0.789, 95% CI 0.633-0.979, P<0.001), use of vasoactive drugs ( OR=2.487,95% CI 1.152-5.184, P=0.008), mean corpuscular hemoglobin concentration (MCHC) ( OR=0.956,95% CI 0.930-0.981, P<0.001) and maximum lactate level ( OR=1.246, 95% CI 1.075-1.440, P=0.004) were independent risk factors of M/S PIVH in the early stage (sensitivity=73.1%, specificity=81.2%, AUC=0.818). The Hosmer-Lemesshow test showed that the model correlated well with the actual incidence of M/S PIVH ( χ2=2.394, P=0.302). The Bootstrap internal validation showed that the model had a realistic estimate of its performances (AUC=0.801). Conclusions:An early prediction model for M/S PIVH can be established based on pregnancy/perinatal history and clinical data within 24 h after birth. The model is helpful for prognosis evaluation and clinical decision-making.
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ObjectiveTo study the possible molecular mechanism of baicalein （BAI）-mediated focal adhesion kinase （FAK） in the regulation of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to inhibit the proliferation and migration of gastric cancer HGC-27 cells. MethodThe gastric epithelial GES-1 cells and gastric cancer HGC-27 cells were respectively treated with BAI （0， 5， 15， 25， and 50 μmol·L-1） for 48 h， and then methyl thiazolyl tetrazolium （MTT） assay was adopted to detect effect of BAI on cell proliferation. Western blot （WB） was employed to detect the expression of FAK and the proteins related to epithelial-mesenchymal transition （EMT） and PI3K signaling pathway after intervention with different concentrations of BAI. The HGC-27 cells stably overexpressing FAK were constructed with lentivirus-mediated transfection technique， and the transfection of FAK was detected through WB and green fluorescent protein （GFP）. The cells were divided into empty vector （NC） group， BAI group， FAK overexpression group， and BAI-treated FAK overexpression group， and cell proliferation activity was detected by MTT assay. The colony formation and cell migration were observed via colony formation assay and Transwell migration assay， respectively. The expression of proteins involved in EMT and PI3K signaling pathways were detected by Western blot. ResultCompared with the NC group， BAI （15， 25 and 50 μmol·L-1） inhibited the proliferation of HGC-27 cells in a dose-dependent manner （P<0.05， P<0.01） while did not affect that of GES-1 cells. BAI （5， 15 and 25 μmol·L-1） down-regulated the expression level of p-FAK （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed up-regulated expression level of FAK in HGC-27 cells. The HGC-27 cells in both NC group and FAK overexpression group had green fluorescence. Compared with NC group， BAI inhibited the growth， colony formation， and migration， while FAK overexpression promoted those of HGC-27 cells. The treatment of FAK overexpression group with BAI inhibited the enhancement of cell proliferation and migration （P<0.05）. WB showed that compared with NC group， BAI （15， 25 μmol·L-1） significantly up-regulated the expression of E-cadherin protein and down-regulated that of Vimentin， Snail， p-PI3K， and p-Akt protein in HGC-27 cells （P<0.05， P<0.01）. Compared with NC group， FAK overexpression group showed down-regulated expression of E-cadherin， up-regulated expression of p-FAK， Vimentin， and Snail， and increased ratios of p-FAK/FAK， p-PI3K/PI3K and p-Akt/Akt （P<0.05）. This phenomenon would be reversed after BAI treatment. ConclusionBAI can affect the proliferation and migration of gastric cancer HGC-27 cells by mediating FAK to regulate PI3K/Akt signaling pathway.
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Background: Disrupted circadian rhythms have been associated with the development of irritable bowel syndrome (IBS). In some IBS patients, the symptoms may present with circadian fluctuations. Enterochromaffin cells (EC cells) and tryptophan hydroxylase 1 (TPH1) - 5 - hydroxytryptamine (5 - HT) signaling pathway are currently recognized as the key pathophysiological mechanism of IBS. Aims: To explore whether Bmal1, the core circadian clock gene, is involved in the occurrence of IBS by regulating TPH1-5-HT signaling pathway in EC cells. Methods: Normal Sprague-Dawley (SD) rats and IBS-model SD rats, as well as wild type (WT) and intestine-specific Bmal1 knockout (Bmal1
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Objective:To explore the effect of applying individualized progressive nutrition guide sheet in postoperative enteral nutrition (EN) for patients with oral cancer.Methods:Using convenient sampling method, 40 oral cancer patients admitted to Sichuan Cancer Hospital from November 2017 to October 2018 were selected as the control group, and 46 from November 2018 to October 2019 were selected as the observation group. Both groups received EN support but the observation group were applied with progressive nutrition guide sheet. The pre- and post-operative body weight, nutrition related indicators, gastrointestinal symptoms, proportion of patients achieving daily target energy intake, patient/family satisfaction and other indicators were compared between the two groups.Results:There were significant differences in preoperative potassium, total protein and albumin at 7 days after operation, prealbumin at 3 and 7 days after operation, potassium at 3 days after operation and sodium at 3 days after operation between the two groups( Z=4.963, P<0.01; Z=5.094, P<0.01; Z=-2.022, P<0.05; Z=4.048, P<0.01; Z=2.14, P<0.05, Z=-6.04, P<0.01, Z=-7.13, P<0.01). The dynamic changes of potassium and sodium in the two groups were compared before operation, 3 days after operation and 7 days after operation ( F=30.20, F= 118.51, all P<0.01). There were significant differences in incidence of abdominal pain, abdominal distension and diarrhea between the two groups ( χ2=6.91, P=0.009, χ2=10.36, P=0.001, χ2=4.71, P=0.03). There were also significant differences in the proportion of patients achieving daily target energy intake at 1 day, 2 days, 3 days, 4 days, 5 days, and 6 days after operation between the two groups ( χ2=41.77, χ2=45.09, χ2=45.71, χ2=40.53, χ2=29.97, χ2=6.11, all P<0.01). Conclusion:The application of progressive nutrition guidelines in early postoperative EN support for patients with oral cancer can help to improve postoperative nutritional status, avoid potassium, sodium and electrolyte disturbance, alleviate postoperative gastrointestinal symptoms, improve the achievement of daily target energy intake and patient/family satisfaction, and promote disease recovery.
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Objective@#To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic.@*Methods@#Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of 2019-nCoV by RT-PCR.@*Results@#Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020.@*Conclusions@#In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.
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The treatment plan for chronic pain often proceeds from a single drug to drug combination therapy. Sinomenine and ligustrazine, natural alkaline substances derived from traditional Chinese medicines, are expected to provide a new choice for combination analgesic therapy strategies. Here we establish a microdialysis sampling and HPLC-MS/MS quantification method for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid. Blood and brain microdialysis probes were implanted in the jugular vein toward the right atrium and left corpus striatum zone (AP +0.2 mm, ML 3.0 mm, DV 3.5 mm) in rats. The blood and brain microdialysis probes were perfused with citric acid buffer solution and Ringer's solution, respectively. Blood and brain extracellular fluid microdialysate were collected at intervals of 20 min at a perfusion rate of 1.5 μL·min-1, and continuously collected for 24 h after administration. The liquid chromatographic separation used a C18-reversed phase chromatographic column (HSS T3 2.5 μm, 2.1 mm×50 mm), the mobile phase was methanol/water (containing 0.05‰ formic acid), and gradient elution was carried out at a flow rate of 0.3 mL·min-1. Mass spectrometric detection used an electrospray ion source, positive ion mode and multi-reaction monitoring method. The selected quantitative ions for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin, amitriptyline and internal standard naloxone were 330/181, 137/80, 172/154, 152/110, 160/142, 278/233 and 328/310 respectively. The specificity, linear range, matrix effect, accuracy, precision, stability and probe recovery were investigated and confirmed to be suitable for the determination of the above drugs in rat blood and brain extracellular fluid microdialysate. The calculated in vivo recovery of microdialysis probes ranged from 19.38% to 25.88%. After intravenous administration of sinomenine (50 mg·kg-1), ligustrazine (50 mg·kg-1), gabapentin (50 mg·kg-1), paracetamol (50 mg·kg-1), pregabalin (50 mg·kg-1) and amitriptyline (40 mg·kg-1) to rats, the peak concentration in the blood microdialysate was in the range of 0.2-10 μg·mL-1. Drug concentrations could also be detected in brain extracellular fluid microdialysate, however with lower levels (peak concentration: 0.1-6 μg·mL-1) than those of blood microdialysates at each time point. In conclusion, this method can be applied to microdialysis sampling and quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rats. The method will promote research in identifying herb-drug pharmacokinetic interactions, as well as safety concerns in combination-therapy strategies.
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The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.
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Animals , Rats , Apoptosis , Brain Diseases/drug therapy , Cerebrospinal Fluid/chemistry , Chromatography, Liquid , Drugs, Chinese Herbal/analysis , Injections , Mass Spectrometry , Signal TransductionABSTRACT
Chuanxiong Qingfengteng mixture (CQM) is an analgesic developed based on clinical evidence and traditional Chinese medicine theory, which majorly consists of Ligusticum chuanxiong and Sinomenium acutum extracts. The current study aims to establish an UHPLC-UV method for the quantification of sinomenine and ligustrazine after CQM administration to rats, mice and cells, and to study the brain permeability of sinomenine and ligustrazine. The selectivity, linearity, accuracy, precision and stability of the established method demonstrated that it was suitable for the determination of sinomenine and ligustrazine in biological samples such as plasma, brain tissue and cellular fluid. After CQM was intravenously administered to rats and mice, both sinomenine and ligustrazine were detected in the brain from 5 min-2 h. The CSF/plasma partition coefficients (Kp, C/P) of each component were higher than those of brain tissue/plasma partition coefficient (Kp, B/P), the Kp, C/P and Kp, B/P of ligustrazine were higher than those of sinomenine. The concentrations between CSF and brain tissue were strongly correlated (Pearson's R>0.86, P<0.001). The unbound fraction in plasma of sinomenine and ligustrazine was 78.92% and 34.07%, respectively. The plasma protein binding rates displayed concentration-independent behavior within their respective in vivo concentration ranges. After CQM co-cultured with Caco-2 cell monolayers, the apparent permeability coefficient (Papp) of sinomenine and ligustrazine were 1.30×10-6 and 3.64×10-6 cm·s-1, respectively, following into the range of the intermediate and high permeability compounds. The efflux ratio (Papp(basolateral→apical)/Papp(apical→basolateral)) of sinomenine and ligustrazine were 0.67 and 0.85, respectively. When combined with P-glycoprotein inhibitor, the Papp of each component did not increase. In conclusion, the UHPLC-UV assay was successfully applied for the brain permeability study of CQM, the components of CQM can be quickly distributed to cerebrospinal fluid and pass through the blood-brain barrier. The brain permeability of ligustrazine is higher than that of sinomenine. The transmembrane transport of sinomenine and ligustrazine may not be affected by efflux transporters. All animal care and use complied with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Experimental Research Center, China Academy of Chinese Medical Sciences.
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This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.
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By studying the relationship between syndromes, physique and MMP-9, IL-6 and MTHFR gene polymorphisms in patients with ischemic stroke,The relationship between MMP-9, IL-6 and MTHFR gene polymorphism was analyzed in patients with ischemic stroke.The data were collected by collecting the data of patients with ischemic stroke, and the statistical analysis was carried out. Syndrome：61 cases of ischemic stroke patients with stroke phlegm stasis syndrome in patients with the highest frequency, a total of 30 cases; Physical constitution： phlegm is ischemic stroke patients prone to physical, a total of 20 cases; The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, Phlegm constitution and physical condition after the onset of symptoms tend to wind phlegm stasis syndrome; Syndrome and MMP-9, IL-6 relationship：The distribution of MMP-9 and IL-6 in patients with qi and phlegm stasis syndrome and qi deficiency and blood stasis syndrome was significantly different from that in Z test (P<0.05). The level of MMP-9 in patients with qi deficiency and blood stasis syndrome was significantly higher than that in patients with wind phlegm and blood stasis syndrome;The level of IL-6 in patients with phlegm and blood stasis syndrome was significantly higher than that in patients with qi deficiency and blood stasis syndrome. Syndrome, constitution and MTHFR gene polymorphism： among the 61 samples, 34 were heterozygous mutations, 15 were pure and mutated, 12 had no mutation, The mutation rate of this locus was 4.08 times that of patients without mutations.The genotype of MTHFR C677T in patients with phlegm dampness tends to be CT genotype. Wind phlegm stasis syndrome in patients with easy to appear after the TT genotype; Yin deficiency syndrome in patients prone to miscellaneous and mutations, the performance of CT genotype; Analysis of the relationship between syndromes and physique in patients with ischemic stroke,Phlegm and dampness, flat quality patients after the onset of easy to show the wind phlegm stasis syndrome; Qi deficiency after the onset of symptoms in patients with Qi and blood stasis. Suggesting that before the onset of such as for the partial physical conditioning, may be on the prevention of ischemic stroke have a certain effect; Analysis of the relationship between syndromes and MMP-9 and IL-6 in patients with ischemic stroke, Wind phlegm stasis syndrome and IL-6 levels are related, Qi deficiency and blood stasis syndrome and MMP-9 levels are related. Analysis of the relationship between syndromes and MTHFR gene polymorphism in patients with ischemic stroke, TT genotype after the onset of symptoms prone to wind phlegm stasis syndrome, CT genotype patients after the onset of easy manifestations of Yin deficiency wind syndrome; Analysis of the relationship between physique and MTHFR gene polymorphism in patients with ischemic stroke, CT genotype is easy to show phlegm.For more in-depth understanding of pathogenesis of ischemic stroke to provide the basis, For the clinical treatment and prevention to provide intervention strategies.
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Stroke is an acute cerebrovascular disease with high morbidity, disability and mortality. The prevention and treatment conditions for stroke is severe all over the world. Antiplatelet aggregation is an effective treatment. Platelet activation factor (PAF) is another important medium in mediating platelet aggregation, which plays an important role in the pathogenesis of stroke. In recent years, PAF receptor antagonists have attracted international attention in the field of stroke prevention and treatment. In this review, we would summarize the classification, mechanism and drug characteristics of PAF receptor antagonists in order to provide the valuable guidance and direction for clinical medicine and research.
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<p><b>OBJECTIVE</b>To observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury.</p><p><b>METHOD</b>The synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process.</p><p><b>RESULT</b>ACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus.</p><p><b>CONCLUSION</b>The synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.</p>
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Animals , Male , Rats , Acetylcholine , Metabolism , Choline , Metabolism , Extracellular Fluid , Metabolism , Hippocampus , Cell Biology , Neurotransmitter Agents , Metabolism , Perfusion , Prefrontal Cortex , Cell Biology , Rats, Sprague-Dawley , Sodium Azide , Pharmacology , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To observe the analgesic effect of CQM on photochemically-induced prosopalgia model rats, and discuss its impact on the exciting amino acid neurotransmitter-glutamate (Glu).</p><p><b>METHOD</b>Male SD rats were randomly divided into the sham operation group and the prosopalgia group. And the latter was subdivided into the model group, the gabapentin group (100 mg kg(-1)), and the CQM low-dose (35 mg x kg(-1)) and CQM high-dose (70 mg x kg(-1)) groups. The mechanical allodynia test was adopted to evaluate the pain behavior of rats, and reflect the efficacy with the mechanical withdrawal thresholds. The rat striatum extra-cellular fluid was collected by brain micro-dialysis. The Glu level of samples was measured by high performance liquid chromatography-fluorescene detector (HPLC-FLD).</p><p><b>RESULT</b>Compared to the control group, the threshold of the mechanical allodynia of the IoN injury group was decreased significantly (P < 0.05), and the concentration of Glu was increased dramatically (P < 0.05). Compared to the model group, the mechanical allodynia of photochemically-induced prosopalgia model rats increased significantly (P < 0.01), with a notable increase in brain Glu concentration (P < 0.05). Compared with the model group, all of mechanical withdrawal thresholds increased. Among them, the CQM high-dose group showed a remarkably growth at three time points (P < 0.05), with the maximum up to (23 +/- 7.3) g. And the gabapentin group showed a remarkably growth at two time points (P < 0.05), with the maximum up to (20.5 +/- 9.2) g. All of the drug groups showed significantly lower Glu concentrations in rat brains than the model group (P < 0.05).</p><p><b>CONCLUSION</b>CQM can ease the mechanical allodynia of photochemically-induced prosopalgia model rats. Its analgesic effect may be related to the decrease of Glu concentrations in striatum extra-cellular fluid.</p>
Subject(s)
Animals , Humans , Male , Rats , Drugs, Chinese Herbal , Glutamic Acid , Metabolism , Neurotransmitter Agents , Metabolism , Pain , Drug Therapy , Metabolism , Rats, Sprague-Dawley , Trigeminal Nerve Diseases , Drug Therapy , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid.</p><p><b>METHOD</b>Male SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group (100 mg x kg(-1)), the sinomenine high dose group (40 mg x kg(-1)) and the sinomenine low dose group (20 mg x kg(-1)). Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA).</p><p><b>RESULT</b>SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration (P < 0.01), significant decrease in cold pain sensitivity score during 30-240 min (P < 0.05). Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P < 0.05), remarkably reduce DA content and DOPAC at 45, 75 and 135 min (P < 0.05), 5-HT content during 45-135 min, DOPAC during 75-165 min (P < 0.05), and 5-HIAA during 45-135 min (P < 0.05).</p><p><b>CONCLUSION</b>Sinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.</p>
Subject(s)
Animals , Male , Rats , Analgesics , Pharmacology , Biogenic Monoamines , Metabolism , Disease Models, Animal , Extracellular Fluid , Morphinans , Pharmacology , Neostriatum , Pathology , Neurotransmitter Agents , Metabolism , Rats, Sprague-Dawley , Sciatic Nerve , Wounds and Injuries , Metabolism , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of Erzhi Pill (二至丸,EZP) on nerve cell apoptosis in senescence model rats.</p><p><b>METHODS</b>The rats model of senescence was established by peritoneal D-galactose injection combined with thymusectomy. Forty SD rats were randomized into four groups, the normal control group, the senescence model group, the EZP treated group, and the vitamins treated group, 10 in each group. The rats were made into senescence model except those in the normal group. In the same time of D-galactose injection, the rats were treated respectively with distilled water, EZP 4.32 g/kg, and vitamins E and C 0.06 g/kg daily for 6 weeks via intragastric infusion. The index of main viscera (as brain, testis, etc.), serum levels of superoxide dismutase (SOD) activity, and total anti-oxidation capacity (T-AOC) were measured after a 6-week treatment. Meanwhile, the cerebral cortex neuronal apoptosis proportion and mitochondrial membrane potential (MMP) were detected by flow cytometry.</p><p><b>RESULTS</b>Both EZP and vitamins E and C treatments showed effects on increasing testis index and serum level of T-AOC, reducing the percentage of neuronal apoptosis in the cerebral cortex, and elevating MMP in the aging rats model.</p><p><b>CONCLUSIONS</b>EZP could inhibit the cerebral cortex neuron apoptosis and maintain the mitochondrial function in the senescent process of rats induced by peritoneal D-galactose injection combined with thymusectomy. It also shows antioxidation effect to some extents.</p>
Subject(s)
Animals , Male , Rats , Aging , Blood , Antioxidants , Metabolism , Apoptosis , Cerebral Cortex , Cell Biology , Drugs, Chinese Herbal , Pharmacology , Matrix Metalloproteinases , Metabolism , Neurons , Cell Biology , Rats, Sprague-Dawley , Superoxide Dismutase , BloodABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of tetramethylpyrazine (TMP) on brain oxidative damage induced by intracerebral perfusion of levodopa (L-DOPA) in rats with Parkinson's disease (PD).</p><p><b>METHODS</b>PD model rats were induced by intracerebral injection of 6-hydroxyl dopamine (6-OHDA) and perfused in brain with L-DOPA using microdialysis technique. Changes in levels of 2,3-dihydroxy benzyl acid (2.3-DHBA) and 2,5-dihydroxy benzyl acid (2,5-DHBA) in striatum of rats, formed by extracellular hydroxyl radical from salicylic acid capturing, were dynamically observed at various time points by HPLC-ED.</p><p><b>RESULTS</b>After treatment with L-DOPA, 2,3-DHBA and 2,5-DHBA in the model group showed significantly higher levels at 6 and 7 time points as compared with those in the sham-operated group at the corresponding time points (P <0.05 or P< 0.01), while these abnormal elevations were significantly inhibited in the TMP treated groups, either in large or small dose (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>TMP could reduce the L-DOPA induced brain oxidative damage in PD rats.</p>
Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents, Non-Steroidal , Therapeutic Uses , Catechols , Metabolism , Chromatography, High Pressure Liquid , Methods , Corpus Striatum , Metabolism , Pathology , Hydroxybenzoates , Levodopa , Microdialysis , Oxidative Stress , Oxidopamine , Parkinson Disease, Secondary , Drug Therapy , Metabolism , Pyrazines , Therapeutic Uses , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the protection mechanism of prepared Polygonum multiflorum (PPMT) in rat brain with sodium azide (NaN3) perfusion.</p><p><b>METHOD</b>Rats were divided into six groups: control, model, PPMT, Duxil and PPMT + Duxil groups. The intracerebral microdialysis and high performance liquid chromatography-post column Immobilized enzyme reactor-electrochemical detection were used to continuously measure extracellular acetylcholine (ACh) and choline (Ch) levels in striatum of freely moving awake rats.</p><p><b>RESULT</b>The extracellular Ach, Ch levels of striatum stayed stable in the control group during the whole observing period, but the ACh levels in the model group were lower significant than that in the control group. The Ach levels of three drug groups were respectively higher significant than that of model group at some time points. While the extracellular Ch level in striatum of the model group increased singnificantly compared with the control group. The Ch levels of the three drug groups were lower significant than that of the model group respectively at certain time points. The effects of PPMT were similar with that of Duxil.</p><p><b>CONCLUSION</b>The prepared P. multiflorum can improve the impaired cholinergic nerve function to exert the effects of brain protection by elevating extracellular Ach level and improving uptake of extracellular Ch. It may provide the experimental evidence to support the idea that P. multiflorum could be brain protective drug to treat retrogressive disease such as dementia.</p>