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OBJECTIVE To investigate the improvement effects and possible mechanism of 7-hydroxyethyl chrysin (7-HEC) on PC12 cell injury induced by hypobaric hypoxia. METHODS The rat adrenal pheochromocytoma cell line PC12 was cultured under low-pressure hypoxia (5%CO2, 94%N2, 1%O2, 54 004 Pa) to investigate the different concentrations of 7-HEC (100, 10, 1, 0.1, 0.01 μmol/L) on the survival rate of hypoxic cells; the effects of 7-HEC(1 μmol/L) on the contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA), superoxide dismutase (SOD) activity, apoptotic rate, cell cycle, and the expressions of cleaved caspase-3, Bcl-2 and Bax were detected. RESULTS Compared with control group, the survival rate of cells in hypobaric hypoxia group was decreased significantly (P<0.01); 10, 1, 0.1 μmol/L 7-HEC could reverse the decrease of cell survival rate caused by hypobaric hypoxia (P<0.05 or P<0.01). Compared with control group, LDH content in supernatant, MDA content in cells, apoptotic rate, the proportion of cells at G1 stage and the protein expression of cleaved caspase-3 were increased significantly in hypobaric hypoxia group, while SOD activity in cells, the proportion of cells at S stage and G2 stage and Bcl-2/Bax ratio were decreased significantly (P<0.05 or P<0.01). Compared with hypobaric hypoxia group, the contents of LDH and MDA, apoptotic rate, the proportion of cells at G1 stage and the expression of cleaved caspase-3 in 7-HEC group were decreased significantly, while SOD activity, the proportion of cells at G2 stage and Bcl-2/Bax ratio were increased significantly (P< 0.01). CONCLUSIONS 7-HEC can significantly increase the survival rate of hypobaric hypoxia cells, reduce the LDH content in supernatant, improve cell cycle arrest, and reduce the rate of apoptosis. Its improvement effects on hypobaric hypoxia cell injury may be related to the inhibition of caspase-3/Bax/Bcl-2 pathway activation.
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Objective To study the possible mechanism of 7-hydroxyethyl chrysin (7-HEC) on high altitude cerebral edema (HACE). Methods A rat model of high altitude cerebral edema was established. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in rat brain tissues were measured. The expression levels of apoptosis, cell cycle and autophagy related proteins were detected by Western blotting to explore the protective effect of 7-HEC on high altitude cerebral edema and its mechanism. Results Compared with the control group, the content of MDA in the brain tissue of the hypoxia model group was significantly up-regulated; the activity of SOD was significantly down-regulated, the relative expression of CyclinD1, CyclinE1, CDK6 and CDK2, apoptotic proteins Bcl-2, PARP, and autophagy protein LC3-B were down-regulated; and the relative expression of apoptotic protein Bax and autophagy protein P62 were up-regulated; the difference was statistically significant (P<0.05); Compared with the hypoxia model group, the content of MDA was down-regulated and the activity of SOD was significantly up-regulated in the 7-HEC administration group. The relative expression of CyclinD1, CyclinE1, CDK6, CDK2, apoptotic proteins Bcl-2, PARP, autophagy protein LC3-B was up-regulated and the relative expression of apoptotic proteins Bax and the relative expression of autophagy protein P62 was down-regulated in the 7-HEC administration group. The difference was statistically significant (P<0.05). Conclusion 7-HEC has a certain protective effect on high altitude cerebral edema, and its mechanism may be related to the regulation of cell cycle, autophagy, apoptosis and oxidative stress pathways.
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To construct a hypobaric hypoxia-induced cell injury model. Rat pheochromocytoma PC12 cells were randomly divided into control group, normobaric hypoxia group and hypobaric hypoxia group. The cells in control group were cultured at normal condition, while cells in other two groups were cultured in normobaric hypoxia and hypobaric hypoxia conditions, respectively. CCK-8 method was used to detect cell viability to determine the optimal modeling conditions like the oxygen concentration, atmospheric pressure and low-pressure hypoxia time. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by microplate method. The apoptosis ratio and cell cycle were analyzed by flow cytometry. The hypobaric hypoxia-induced cell injury model can be established by culturing for 24 h at 1% oxygen concentration and 41 kPa atmospheric pressure. Compared with the control group and normobaric hypoxia group, the activity of LDH and the content of MDA in hypobaric hypoxia group were significantly increased, the activity of SOD was decreased, the percentage of apoptosis was increased (all <0.05), and the cell cycle was arrested in G0/G1 phase. A stable and reliable cell injury model induced by hypobaric hypoxia has been established with PC12 cells, which provides a suitable cell model for the experimental study on nerve injury induced by hypoxia at high altitude.
Subject(s)
Animals , Rats , Cell Hypoxia , Hypoxia , Malondialdehyde , PC12 Cells , Superoxide Dismutase/metabolism摘要
: To investigate the protective effect of 7-hydroxyethyl chrysin (7-HEC) on rats with exercise-induced fatigue in hypobaric hypoxic condition.Forty healthy male Wistar rats were randomly divided into four groups with 10 rats in each group: control group, model group, chrysin group and 7-HEC group. The rats in control group were raised at local altitude but other three groups were raised in a simulating altitude of for hypobaric hypoxia treatment. The chrysin group and 7-HEC group were given chrysin or 7-HEC by gavage for respectively; while the control group and model group were given the same amount of sterilized water. The weight-bearing swimming tests were performed 3 d later, and the weight-bearing swimming time was documented. After rats were sacrificed, the liver and skeletal muscle tissue samples were taken for pathological examination and determination of lactate, malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glycogen levels. Blood urea nitrogen was also determined. Compared with the model group, weight-bearing swimming times were significantly prolonged in 7-HEC group [ vs. (4.04±1.30) min, <0.01]; pathological changes in liver and skeletal muscle tissue were attenuated; generation rate of blood urea nitrogen vs. 0.60) mmol·L·min, <0.05], lactate [liver: (0.14±0.05) vs. (0.10±0.03) mg·g·min, skeletal muscle: vs. (0.18±] and MDA [liver: (0.48) vs. (0.78±0.28) nmol·mg·min, skeletal muscle: (0.87±0.19) vs. (0.63±0.11) nmol·mg·min] were significantly reduced (all < 0.05); glycogen content [liver: (15.16±2.69) vs. skeletal muscle: (1.46±0.49) vs.0.48) mg/g] and T-SOD [liver: (1.87±0.01) vs. (2.68±0.12) U/mL, skeletal muscle: 0.42) vs. 0.96) U/mL] were significantly improved (all <0.05). 7-HEC has significant protective effect on the rats with exercise-induced fatigue in hypobaric hypoxia condition.
Subject(s)
Animals , Male , Rats , Altitude , Fatigue/prevention & control , Flavonoids , Hypoxia , Rats, Wistar摘要
Cerebrospinal fluid surrounds and supports the central nervous system, including the ventricles and subarachnoid spaces. Cerebrospinal fluid should be an important source of biomarkers for central nervous system diseases because it is in direct contact with the central nervous system. Many studies are reported on cerebrospinal fluid proteomics, highlighting many recent progresses. Here, we review recent advances in proteomics technology and clinical application of cerebrospinal fluid.
Subject(s)
Biomarkers , Cerebrospinal Fluid Proteins , Proteome , Proteomics摘要
Objective To investigate the anti-hypoxia effects of octacosane and the petroleum ether extract from Saus-surea Involucrate(PESI)on the water,sugar,lipid and protein metabolism of mice at simulated high altitude.Methods The healthy adult male BALB/C mice were randomly divided into normal control group,hypoxic model group,acetazolamide group, the petroleum ether of Saussurea involucrata group and octacosane group.Drugs were administered i.v 20 mins before the mice were exposed to a simulated high altitude of 6 000 m for 8 hours in an animal decompression chamber.The mice were sacrificed at the end of 8 hours.Organ water content,organ indexes and metabolism indicators of sugar,protein and lipid were deter-mined.Results The edema of heart,brain and lung was reduced notably(P<0.05,P<0.01)in the mice received PESI at 200 mg/kg and octacosane at 100 mg/kg.In the treated groups,the increase of blood sugar,muscle glycogen,TG(triglycer-ide),TC(total cholesterol)were all significantly inhibited,the decrease of liver glycogen,the protein content of heart and brain was also remarkably blocked(P<0.05,P<0.01).Conclusion PESI and octacosane effectively regulate the metabolism of hypoxic mice and reserve the body′s energy for survival by lowering the basic metabolism.
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Objective To study pharmacodynamics of the effective anti-hypoxia components in the petroleum ether ex-tract of Saussurea Involucrate(PESI)and octacosane.Methods PESI and octacosane were first evaluated by normobaric hy-poxia model,acute decompression model and followed by chemical induced hypoxic models with potassium cyanide,sodium ni-trite and isoprenaline hydrochloride poisoning.Results PESI and octacosane can effectively prolong the survival time of hypo-baric hypoxic mice(P<0.01)and reduce the mortality of acute hypobaric hypoxia mice(P<0.01)in a dose-dependent man-ner.Anti-hypoxic potency of PESI and octacosane obtained by chemical induced hypoxic model indicated that they significantly increase survival time(P<0.05)of hypoxia mice than acetazolamide.Conclusion PESI and octacosane have good anti-hypoxia activity.
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Objective To investigate the effect of hypoxia with cold on the heart and brain damage in rats by simulating 6 000 m high altitude at different exposure time,established a rat model of acute mountain sickness for the related mechanism studies.Methods 32 healthy male Wistar rats were randomly divided into normal control group,hypoxia with cold 1 d,3 d and 5 d group,8 rats in each group.The normal control group was kept in the plain environment(1 500 m)without any treat-ment.The other three groups were placed in large hypobaric hypoxia chamber to simulate 6 000 m altitude with different ex-posed times.HE staining was used to observe the pathological changes of heart and brain tissue.The changes of biochemical indexes were measured to evaluate the damage of heart and brain tissue at different hypoxia times.Results HE staining showed that hypoxia with cold induced rat heart and brain damage with different degrees.The myocardial tissue damage was in-creased with exposure time.The most serious brain damage happened in day 3.Compared with the normal control group,the content of MDA and LD in the myocardial tissue of hypoxia rats were significantly increased(P<0.05 or P<0.01)with pro-longed time,while the contents of GSH,T-SOD and the activity of Na+K+-ATPase were reduced(P<0.05 or P<0.01). The content of MDA in brain tissue was significantly increased at day 1 and day 3(P<0.05 or P<0.01).LD content was sig-nificantly increased(P<0.05)with time.The content of GSH,the activity of T-SOD and Na+K+-ATPase were significantly reduced in day 3(P<0.05).Conclusion Simulating an altitude of 6 000 m caused obvious damage on the heart and brain tis-sues of rats.The degree of damage was related to the exposure time to hypoxia with cold.The decrease of body′s antioxidant capacity,the increase of free radicals and energy metabolism disorders are important factors leading to heart and brain injury.
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Objective To investigate anti-hypoxia activity and protective effects of Lishukang capsule on rat brain tissue at simulated high altitude hypoxia.Methods The anti-hypoxic activity of Lishukang capsule was evaluated with normobaric hypoxia test and acute hypobaric hypoxia test in mice.In addition,rats were exposed to large hypobaric hypoxia chamber stim-ulating 8 000 m altitude.The pathological changes of rat brain tissue before and after hypoxia were observed.The oxidative stress indicators and metabolism parameters in brain were measured.Results The low,medium and high Lishukang doses can effectively prolong the survival time of mice(P<0.01)in the dose dependent manner.The medium and high Lishukang doses were significantly better than those of Rhodiola rosea capsules(P<0.05 or P<0.01).The low,medium,high Lishukang dose groups reduced the mortality of acute hypobaric hypoxia mice(P<0.01)with dose dependent effects.The mice mortality in medium and high dose groups was lower than that of Rhodiola rosea group(P< 0.01).Compared with normal control group,the hypoxic model rats exhibited pathological injury in the brain tissue after exposure to hypobaric hypoxia stimulating 8 000 m altitude.The contents of MDA,H2O2,NO,LD and LDH activity increased significantly(P<0.05 or P<0.01), while the activities of SOD,CAT,GPX were significantly decreased(P<0.05 or P<0.01).After pretreatment with Lishu-kang capsule,the pathological damage of rat brain tissue was alleviated and the content of MDA,NO in the brain tissue was re-duced(P<0.05 or P<0.01).The levels of H2O2,LD content and LDH activity in medium and high dose groups were signifi-cantly decreased(P<0.05 or P<0.01).The activities of SOD,CAT and GPX in high dose group were significantly increased(P<0.05).Conclusion Lishukang capsule has good anti-hypoxia activity.It provides protective effect for the injuries induced by hypobaric hypoxia in rats.The mechanism may related to the improvement of antioxidant capability,reduction of free radical damage and amelioration of energy metabolism.
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Objective To achieve primary intervention from early on the analysis concerning correlations between BI-RADS classification and the factors that might influence it was conducted. Methods In this paper, the women involved in the 7204 cases of physical examinations in our hospital(over the past 5 years)were chosen as the subjects investigated. The correlations between their breast ultrasounography results and the factors such as age,BMI,triglycerides,total cholesterol,glucose,and uterine status were analyzed. The breast report used the Breast imaging reporting and data system(also known as BI-RADS)of the American Society of Radiology to inter-pret the results. Chi-square test and logistic multivariate analysis of data were analyzed by SPSS 13 statistical soft-ware. Results The age,triglyceride,total cholesterol,HDL and glucose were not the factors influencing BI-RADS classification(P>0.05);BMI(P=0.004)and uterine status(P=0.000)turned out to be the independent factors. Low body weight[odds ratio(OR)= 0.696,95%Confidence interval(CI)= 0.502 ~ 0.966],overweight (OR=0.217,95%CI=0.142~0.333),and obese(OR=0.123,95%CI=0.066~0.231)were negatively correlat-ed with it. Hysterectomy(OR = 19.189,95%CI = 14.055 ~ 26.198),(OR = 4.384,95%CI = 3.499 ~ 5.492), uterine fibroids ,menopausal uterus were found to be the risk factors(OR = 3.283 ,95%CI = 2.374 ~ 4.541). Conclusion For the premenopausal women,being overweight or underweight can help reduce the risk of getting breast diseases. However,those suffering absence of uterus,or uterine fibroids,or in their menopausal period,are supposed to be among the high-risk group of breast cancer for regular screening.
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OBJECTIVE:To compare the effects of prophylactic application of 3 different antibiotics on prognosis in patients underwent breast lesion resection. METHODS:1 066 patients with breast lasion resection from 12 hospitals of Shaanxi province were divided into trial group(360 cases),control group A(352 cases)and control group B(354 cases)according to random num-ber table. Trial group was given first generation cephalosporin cefazolin;control group A was given second generation cephalospo-rin cefuroxime;control group B was given third generation cephalosporin cefoperazone sodium and tazobactam sodium. The dosage regimens of 3 groups were as follows:relevant drug 2 g added into 0.9%Sodium chloride injection 100 ml,ivgtt,0.5 h before sur-gery,medication course≤24 h after surgery in trial group. Those indexes of 3 groups were observed,such as post-operative ADR, incision healing,infection,hospitalization duration,phamaceutical costs per capita. RESULTS:There was no statistical signifi-cance in the rate of incision healing and the rate of post-operative infection among 3 groups(P>0.05). The incidence of post-opera-tive ADR,hospitalization duration and phamaceutical costs per capita in observation group were significantly lower or shorter than in control group A and B,with statistical significance(P<0.05). CONCLUSIONS:Cefazolin is better than cefuroxime and cefo-perazone sodium and tazobactam sodium to reduce the postoperative adverse reaction,antibiotics cost per capita and hospital drug cost per capita,shorten the hospitalization duration.
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Objective To observe the effectiveness and mechanism of Xiaoyao San (Xiaoyao Powder for Soothing Liver and Relieving Depression) in improving depression-like behavior of rats. Methods Male Wistar rats were randomized into normal group, model group, Xiaoyao San (1.9 g·kg-1·d-1) group, and fluoxetine (2 mg·kg-1·d-1) group. The rats were exposed to chronic unpredictable mild stress ( CUMS) to induce rat depression-like behavior. Field test was performed for the observation of effect of Xiaoyao San on rat depression-like behavior, Luminex liquid chip system was applied to detect the serum cytokines, and the amount and size of rat hepatic sinusoidal endothelial window were examined under electron microscope, and hepatic indoleamine 2, 3-dioxygenase ( IDO) and tryptophan 2, 3 -dioxygenaes ( TDO) expression levels were detected by immunohistochemical and Western blot methods. Results Xiaoyao San showed obvious effect on increasing sugar water consumption, the number of crossing the blocks and erection frequency in rats, decreasing serum levels of tumor necrosis factor alpha ( TNF-α) and interleukin 6 ( IL-6) , increasing the amount of hepatic sinusoidal endothelial window, promoting hepatic sinusoidal endothelial vascularization, and reducing TDO and IDO expression ( P<0.05 or P<0.01). Conclusion Xiaoyao San exerts obvious effect on improving rat depression-like behaviors, and the mechanism is probably related with the decrease of inflammatory factors, inhibition of IDO pathway, and improvement of hepatic sinusoidal endothelial function.
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Mitochondria are the main places of cellular respiration as well as the citric acid cycle and oxidative phospho‐rylation .It plays an important role in controlling the life and death of cells .Mitochondrial dysfunction leads to a series of human diseases such as ischemia‐reperfusion injury ,sepsis and diabetes .Mitochondrial become an attractive target for drug transporters strategy and therapeutic targets for neurodegeneration .Although the molecular mechanisms responsible for mitochondria media‐ted disease processes are not fully elucidated yet ,the oxidative stress appears to be critical .Accordingly ,strategies are being de‐veloped for the targeted delivery of antioxidants to mitochondria .The prospect of development of mitochondrial targeted drugs with anti‐oxidative stress protection is tempting .Mitochondrial targeting antioxidants were the antioxidant drugs which took mi‐tochondria as the target site .In this review ,weintroduced the conception and classification of mitochondrial targeted antioxidants and the research progress of disease treatment by mitochondrial targeted antioxidants .
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<p><b>OBJECTIVE</b>To analyze the correlation between mitral regurgitation grading and left ventricular ejection fraction in elderly patients (>60 years of age) in a 2-year follow-up.</p><p><b>METHODS</b>A total of 455 patients with the diagnosis of at least mild mitral regurgitation by echocardiography were divided into ischemic mitral regurgitation (IMR) group and non-ischemic regurgitation (NIMR) group. The patients were followed up with echocardiography every 6 months and the data were analyzed at the end of 24 months.</p><p><b>RESULTS</b>Mitral regurgitation grade was inversely correlated with left ventricular ejection fraction (LVEF). Patients with moderate and severe IMR had a lower LVEF than those with NIMR (P<0.05). After adjustment for age, sex, body mass index, high blood pressure, diabetes, atrial fibrillation and cardiomyopathy, the mean LVEF at 2 years was lowered by 2.7% (1.4%-4.1%), 2.7% (1.3%-4.0%), and 5.2% (3.5%-6.9%) in mild, moderate and severe IMR patients, respectively (P<0.04), and by 3.2% (1.6%-4.8%), and 3.0% (1.4%-4.5%), and 1.7%(-0.5%-3.9%) in mild, moderate and severe NIMR patients (P=0.30).</p><p><b>CONCLUSION</b>The mean LVEF in IMR patients is significantly lowered compared to that in NIMR patients. The grade of mitral regurgitation is inversely correlated with the regurgitation area in IMR patients. Stratified management might help improve LVEF in severe IMR patients.</p>
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Aged , Aged, 80 and over , Female , Humans , Male , Follow-Up Studies , Mitral Valve Insufficiency , Stroke Volume , Ventricular Dysfunction, Left摘要
<p><b>OBJECTIVE</b>To study the effects of Chaiqiyigan Granula (CG) and Taxol on the growth of hepatocellular carcinoma (HCC) xenografts and expression of Bax, p53 and VEGF in nude mice.</p><p><b>METHODS</b>Whole-body fluorescence imaging was used to visualize the growth of HCC in nude mice bearing hepG2/EGFP cell xenograft. Immunohistochemistry was used to determine the content of Bax, p53 and vascular endothelial growth factor (VEGF) in the tumor tissues.</p><p><b>RESULTS</b>Compared with normal saline, Taxol alone and in combination with CG significantly inhibited the growth of HCC xenografts in the nude mice. The combined treatment with CG and Taxol produced a stronger inhibitory effect on the tumor growth than Taxol alone in the third and fourth weeks. The volume and weight of the xenografts were decreased in the combined treatment group compared with those in saline treatment group. CG combined with Taxol increased the expression of Bax and reduced the expression of p53 and VEGF in the tumor xenografts.</p><p><b>CONCLUSION</b>CG can enhance the inhibitory effects of Taxol on the growth of HCC xenografts, and this effect is related to the up-regulation of Bax and down-regulation of p53 and VEGF expression in the tumor.</p>
Subject(s)
Animals , Humans , Mice , Carcinoma, Hepatocellular , Metabolism , Pathology , Cell Line, Tumor , Drugs, Chinese Herbal , Pharmacology , Liver Neoplasms , Metabolism , Pathology , Mice, Nude , Optical Imaging , Paclitaxel , Pharmacology , Tumor Suppressor Protein p53 , Metabolism , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein , Metabolism摘要
<p><b>OBJECTIVE</b>To study the chemical constituents of Abelmoschus esculentus.</p><p><b>METHOD</b>The chemical constituents were isolated and purified by chromatography on silica gel and recrystallization. The chemical structures were elucidated on the basis of physicochemical properties and spectral data.</p><p><b>RESULT</b>Fourteen compounds were isolated and identified as 6-hydroxy-stigmasta-4-en-3-one(1), 6-hydroxy-stigmasta4,22-dien-3-one(2), stigmasta-5-en-3-ol-7-one(3), stigmasta-5, 22-dien-3-ol-7-one(4), stigmast-5-en-3, 7-diol(5), stigmast-5, 22-dien-3, 7-diol(6), stigmast-4, 22-dien-3, 6-dione(7), stigmasta-4, 22-dien-3-one(8), ergosta-7, 22-dien-3-ol(9), cycloart-25-en-3,24-diol(10), lupeol(11), aurantiamide acetate (12), stigmasterol(13), hexadecanoic acid (14).</p><p><b>CONCLUSION</b>Compounds 1-12 are obtained from the genus Abelmoschus plant for the first time and also from the Malvaceae for the first time.</p>