利培酮增加高血压大鼠脑卒中易感性及机制分析-risperidone increases the susceptibility to stroke in hypertensive rats and its mechanism analysis.docx

Risperidone enhances the vulnerability to strokein hypertensive ratsAbstractBackground－Stroke is the second most common cause of death and major cause of disability worldwide. Risperidone is an atypical antipsychotic drug. Clinical studies indicated that risperidone may increase the risk of stroke. While, the possiblemechanisms were not explained and animal models were not copied successfully to this side-effect. The present work was designed to affirm whether risperidone could enhances the vulnerability to stroke in hypertensive rats and find out the possible mechanisms.Methods－Experiment 1: Effect of risperidone on brain ischemia after MCAO and onsurvival time of rats. Forty eight male SHR-SPs at the age of 20-22 weeks were divided randomly into 3 groups, and received risperidone of 0, 0.8 mg/kg, and 2.4 mg/kg respectively. One month later, their body weights were recorded, and their SBP was measured using tail-cuff plethysmography until they were all carried out MCAO. The percentage of infarct area in hemisphere was calculated. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of malondialdehyde (MDA) were determined. Cerebral ultramicroscopic structure morphology was observed using electron microscope before and after MCAO respectively. Thirty eight male WKYs at the age of 20-22 weeks carried out the same protocol as SHR-SPs above except for one group of 0.8 mg/kg. Twenty male SHRs at the age of 20-22 weeks received risperidone of 0 and 2.4 mg/kg respectively for 1 month only for body weights, SBP and infarct area analysis. Another forty five male SHR-SPs received risperidone as SHR-SPs above, only for life-long treatment. Rats were observed twice daily (at 8 AM and 6 PM) and the survival time (from birth to death) of every rat was recorded.Experiment 2: Effect of risperidone on proinflammatory cytokines and apoptosis in the cerebral cortex nerve cells. First, primary cultures of cortical microglias from WKYs w