坎地沙坦酯对鱼藤酮致帕金森病大鼠的保护作用

Protective effect of candesartan cilexetil on rotenone-induced Parkinson＇s disease in rats

目的 研究坎地沙坦酯对鱼藤酮致帕金森病（PD）大鼠的影响. 方法 10周龄雄性Lewis大鼠40只按照随机数字表法分为对照组、鱼藤酮组、鱼藤酮＋坎地沙坦酯组和坎地沙坦酯组,每组10只.100 g/L水合氯醛麻醉充分后,微量渗透泵包埋于各组大鼠背部皮下.鱼藤酮[2.5～3.0 mg/（kg· d）]溶于二甲基亚砜和聚乙二醇（1∶1）混合液中,埋于鱼藤酮组大鼠微量渗透泵中;余3组给予等质量的生理盐水装于微量渗透泵中;鱼藤酮＋坎地沙坦酯组大鼠同时给予坎地沙坦酯（混于0.5％甲基纤维素中）每天上午8时～12时灌胃[1 mg/（kg· d）],对照组给予等体积生理盐水灌胃.行为学检测评定运动功能等损害症状;免疫组化染色检测大鼠黑质部位酪氨酸羟化酶（TH）和α-共核蛋白表达情况;Western blotting检测黑质部位α-共核蛋白表达水平. 结果 分组4周后鱼藤酮组大鼠体质量明显减轻,降至（297.3±12.2）g;黑质部位TH阳性细胞显著减少,降至（377.0±41.6）个/mm2;α-共核蛋白表达显著增加,达到0.75±0.02;鱼藤酮＋坎地沙坦酯组对应的各项值分别为（337.2±26.3）g、（639.7 ±46.0）个/mm2、0.57±0.01;二者差异有统计学意义（P＜0.05）.Western blotting结果与之一致. 结论 坎地沙坦酯能够通过减少TH阳性细胞凋亡及α-共核蛋白沉积起到保护PD大鼠作用.

Objective To investigate the effect of candesartan cilexetil on rotenone-induced Parkinson＇s disease （PD） in rats.Methods Forty 10-week-old male Lewis rats were chosen in our study and equally randomized into control group,rotenone group,rotenone＋candesartan cilexetil group and candesartan cilexetil group （n=10）; rotenone （2.5-3.0 mg/[kg· d]） was given for 4 weeks to the rats of rotenone group and rotenone＋candesartan cilexetil group by subcutaneous osmotic minipumps implantation under the back; rats in the rotenone＋candesartan cilexetil group and candesartan cilexetil group were orally administered candesartan cilexetil.Neurological behavioral measurements were performed to evaluate the motor features; tyrosine hydroxylase （TH） and α-synuclein immunoreactivities in the substantia nigra pars compacta （SNc） were observed.Protein level of α-synuclein was determined by Westem blotting.Results The weight of rats in the rotenone group reduced to （297.3±12.2） g,with significant difference as compared with that of the other three groups （P〈0.05）; decreased TH immunoreactivity （377.0±41.6） cells/mm2） and increased α-synuclein immunoreactivity （0.75±0.02） in the SNc of rats in the rotenone group was noted,enjoying significant differences as compared with the other three groups （P〈0.05）; these values in the rotenone＋candesartan cilexetil group were （337.2±26.3） g,（639.7±46.0） cells/mm2 and 0.57±0.01,respectively （P〈0.05）.Western blotting confirmed that rotenone up-regulated the expression ofα-synuclein in the SNc,and candesartan ceilexetil markedly attenuated the increase （P〈0.05）.Conclusion Candesartan cilexetil can protect rotenone-induced PD in rats through decreasing TH-positive cell apoptosis and α-synuclein deposition.