尼可地尔对抑郁模型大鼠心肌KATP通道的影响

目的 观察尼可地尔对抑郁模型大鼠心肌损伤的保护作用机制及对K_ATP通道蛋白Kir6.2和SUR2开放的影响。方法 通过建立慢性温和不可预知应激(CMS)致抑郁大鼠模型,随机将大鼠分为对照组、CMS组及尼可地尔组(0.1 mg/kg),各12只。各组大鼠分别饲养2周、4周、6周及8周。采用蛋白印迹法检测大鼠心肌损伤心肌K_ATP通道蛋白Kir6.2和SUR2表达水平;采用动物多导生理记录仪记录大鼠心率、心率变异性改变及Nagar-Olsen病理学染色观察大鼠心肌病理损伤。结果 与对照组比较,CMS组大鼠下丘脑及海马体5-羟色胺含量下降,KATP通道蛋白Kir6.2和SUR2表达水平升高(P<0.05或P<0.01);与CMS组比较,尼可地尔组大鼠下丘脑及海马体5-羟色胺含量升高(P<0.05),K_ATP通道蛋白Kir6.2和SUR2表达水平下降(P<0.01)。病理染色及动物生理记录仪显示,尼可地尔组大鼠心功能明显改善且与对照组持平。结论 尼可地尔通过抑制K_ATP通道开放及Kir6.2和SUR2表达,从而发挥保护心肌细胞的作用。

Effects of Nicorandil on Myocardial KATP Channel in Rats with Depression

Objective To observe the protective mechanism of nicorandil against myocardial injury in rats with depression and its effect on the opening of K_ATP channel proteins Kir6.2 and SUR2.Methods The rats with depression were induced by chronic unpredictable mild stress (CMS) to establish models.The rats were randomly divided into control group,CMS group,and nicorandil group (0.1 mg/kg).The rats in each group were fed for 2 weeks,4 weeks,6 weeks and 8 weeks,with 12 rats in each group.The expressions of myocardial K_ATP channel protein Kir6.2 and SUR2 were detected by Western Blotting.The heart rate and heart rate variability were recorded by animal poly conductance physiological recorder.The pathological injury of myocardium in rats was observed by Nagar-Olsen pathological staining.Results Compared with rats in the control group,5-HT in hypothalamus and hippocampus in the CMS group decreased,and the expressions of KATP channel proteins Kir6.2 and SUR2 increased(P<0.05 or P<0.01).Compared with rats in the CMS group,5-HT in hypothalamus and hippocampus of the nicorandil group increased(P<0.05),and the expressions of K_ATP channel proteins Kir6.2 and SUR2 decreased(P<0.01).Pathological staining and animal physiological recorder showed that cardiac function of rats in nicorandil group was significantly improved and as the same as that in control group.Conclusion Nicorandil could protect cardiomyocytes by inhibiting the opening of K_ATP channels and the expression of Kir6.2 and SUR2.