Amyloid beta-protein induces apoptosis of neurons in rat hippocampus and expression changes of cyclophilin A in these neurons / 中华神经医学杂志

Objective To explore the neuron injury in rat hippocampus induced by Aβ25-35 and the cyclophilin A (CyPA) expression changes in these neurons. Methods Sixty healthy Wister rats were equally randomized into experimental group and control group (n=30); AD rat models in the experimental group were established by injection of Aβ25-35 into the bilateral hippocampus of rats,and rats of the control group were received NS injection. The morphological features of neurons in the CA1 area of hippocampus were observed by HE staining; the neuron apoptosis was determined with TUNEL staining; the mRNA and protein expressions of CyPA were detected by PT-PCR and Western blotting,respectively. Results Aβ25-35 caused damage and apoptosis of neurons in the CA1 area of hippocampus; with time being prolonged,the cell injury aggravated and apoptosis increased in the CA1 area ofhippocampus; significant differences were noted as compared with those in control group 1,7 and 14 d after the inducement (P＜0.05).After injection of Aβ25-35 into the hippocampus of rat,the mRNA and protein expressions of CyPA were obviously changed:in early stage,the expressions increased,and then,the expressions decreased gradually; significant differences were noted as compared with those in control group 1 and 7 d after the inducement (P＜0.05); the protein expression of CyPA in the experimental group 14 d after the inducement was significantly decreased as compared with that in the control group (P＜0.05). Conclusion Aβ25-35 plays a neurotoxicity role through aggravating the apoptosis of neurons; and the increment of CyPA expressions maybe play an endogenously protective role in these damage.

Effects of cyclophilin A on apoptosis of PC12 cells induced by Aβ25-35 and its mechanism / 中华神经医学杂志

Objective To explore the effect of cyclophilin A (CyPA) on apoptosis of PC 12 cells induced by Aβ25-35 and its potential mechanism. Methods PC 12 cells were divided into normal control group (0 μmol/L Aβ25-35), Aβ25-35 inducement group (10 μmol/L Aβ25-35) and drug protection groups (0.1, 1,10 and 100 nmol/L CyPA+10 μmol/L Aβ25-35). Cells in the drug protection groups were pretreated by CyPA of different concentrations for 30 min, and then co-cultured with Aβ25-35 We evaluated the survival rate of PC12 cells with MTT assay, analyzed the apoptosis of PC12 cells with Hoechst33258 staining, and detected the mRNA expressions of Bcl-2 and Bax with PT-PCR and the protein levels of Bcl-2 and Bax with Western blotting. Results Cells pretreated wth CyPA of 1, 10 and 100 nmol/L enjoyed an obvious elevation of survival rate of PC 12 cells, a significant reduction of apoptosis induced by Aβ25-35,an obvious increase of mRNA expression of Bcl-2 and protein level of Bcl-2, and a statistical decrease of mRNA expression of Bax and protein level of Bax as compared with those cells of the Aβ25-35 inducement group (P<0.05);and these effects were dose-dependent. Conclusion CyPA could resist the toxic role of Aβ25-35 on PC 12 cells and reduce the apoptosis in a dose-dependent manner by up-regulation of anti-apoptosis gene Bcl-2 and down-regulation of apoptosis gene Bax.

Protective effect of cyclophilin A against Alzheimer's amyloid beta-peptide (25-35)-induced oxidative stress in PC12 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>beta-amyloid peptide (Abeta) is considered responsible for the pathogenesis of Alzheimer's disease (AD). Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excessive production of reactive oxidative species (ROS) and apoptosis. Cyclophilin A (CypA), exhibits antioxidant properties and protects neurons against oxidative stress induced injury. This study was conducted to demonstrate whether CyPA added to cultured PC12 cells could alleviate Abeta-induced oxidative stress and protect them from apoptosis.</p><p><b>METHODS</b>PC12 cells were pre-incubated for 30 minutes with recombinant human cyclophilin A (rhCyPA) in 0.1 nmol/L, 1.0 nmol/L, 10 nmol/L and 100 nmol/L and then incubated with 10 micromol/L Abeta(25-35). In every group, cell viability, apoptotic morphology, apoptotic rate, intracellular ROS accumulation, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of PC12 cells and mitochondrial transmembrane potential were detected. Subsequently, the expression of the active form of caspase-3 was determined by Western blotting.</p><p><b>RESULTS</b>It was shown that cultures treated with 1.0 nmol/L, 10 nmol/L or 100 nmol/L rhCyPA + Abeta(25-35) had significantly higher cell viability and a lower rate of apoptosis compared with the cultures exposed only to Abeta(25-35). In addition, rhCyPA attenuated Abeta(25-35)-induced overproduction of intracellular ROS and Abeta(25-35)-induced a decrease in activity of the key antioxidant enzymes SOD and GSH-Px. Furthermore, rhCyPA also attenuated Abeta(25-35)-induced mitochondrial dysfunction and the activation of caspase-3.</p><p><b>CONCLUSION</b>CyPA may act as an ROS scavenger, and prevent Abeta(25-35)-induced neurotoxicity through attenuating oxidative stress induced by Abeta(25-35).</p>

Study on the influencing factors to cerebral stroke in a region with high prevalence rate of hypertension / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the influencing factors on cerebral stroke in Zhangwu county, Liaoning province, a region with high hypertension prevalence rate.</p><p><b>METHODS</b>By cluster sampling method, 5208 adults ( > 18y. ) from 11 villages of 6 towns were registered. General information, common risk factors of cerebral stroke about these persons was recorded. Blood pressure together with several biochemistry indicators was determined. Data were analyzed by SPSS 10.0 software.</p><p><b>RESULTS</b>Standardized prevalence of cerebral stroke in this region was 3.10%, and the difference between males and females was significant. Prevalence rate was increasing with age. Multiple-factor analysis revealed that the incidence rate of cerebral stroke was related to high blood pressure, high diastolic pressure, pulse pressure, age, high-density lipoprotein cholesterol (HDL-C) and low-DL-C (LDL-C) level with OR values of 95% CI as 2.958 (1.783-4.907), 2.803 (1.934-4.062), 1.154 (1.056-1.261), 1.080 (1.063-1.097), 0.390 (0.235-0.647) and 1.422 (1.008-2.006) respectively.</p><p><b>CONCLUSION</b>High blood pressure, in particular high diastolic pressure, pulse pressure and LDL-C level were main risk factors of cerebral stroke in Zhangwu countryside. However, HDL-C level was a protective factor. No new risk factors were discovered.</p>