阿托伐他汀对大鼠心肌缺血再灌注损伤心肌保护的内质网应激途径研究

The endoplasmic reticulun stress signaling pathways for Atorvastatin in protection of myocardium in ischemia/reperfusion injury model rats

目的通过观察阿托伐他汀对大鼠心肌缺血再灌注损伤后GRP78和GADD153蛋白表达的影响,探讨阿托伐他汀心肌保护的内质网应激途径。方法 SD大鼠54只随机分为阿托伐他汀干预组24只[灌喂20mg/(kg.d)]、模型对照组24只(0.9%氯化钠溶液灌喂2ml/d)和假手术组6只(0.9%氯化钠溶液灌喂2ml/d),制作大鼠心肌再灌注损伤模型。通过TUNEL检测心肌细胞凋亡,免疫组织化学检测GRP78和GADD153表达变化。结果相邻各时间点比较,阿托伐他汀干预组大鼠心肌细胞凋亡明显比模型对照组减少(P<0.01)。在相应时间点,干预组的GRP78蛋白表达水平比模型对照组升高(P<0.05),同时GADD153的蛋白表达水平明显比模型对照组下降(P<0.01或P<0.05)。结论通过内质网应激途径可能是阿托伐他汀发挥在心肌再灌注后损伤的保护作用机制之一。

Objective To observe the effects of Atorvastatin on the expression of GRP78 and GADD153 proteins in rats with schemia/reperfusion injury, so as to explore the the endoplasmic reticulun stress signaling pathways for Atorvastatin in protection of myocardium. Methods 54 SD rats were randomly divided into the Atorvastatin intervention group （ n = 24） ： the rats were infused orally with Atorvastatin, 20 mg/（kg· d） ; the model control group （ n =24）： the rats were infused orally with 0.9% sodium chloride solution, 2ml/d; the pseudo-operation group （ n = 6） ： the rats were infused orally with 0.9 % sodium chloride solution, 2ml/d. The schemia/reperfusion injury rats models were produced. The TUNEL kit was used to detect myocardial ceils apotosis. The immunohisto- chemistry technique was used to detect GRP78 and GADD153 proteins. Results The Atorvastatin intervention group yielded less myocardial cells apoptosis at adjacent time points, compared to the model control group （ P 〈0.01）. At corresponding time point, the elevated GRP78 proteins were obtained in Atorvastatin intervention group, compared to the model control group （ P 〈 0.05）, while the levels of GADD153 protein decreased signifi- cantly, compared to the the model control group （ P 〈 0.01 or P 〈 0.05）. Conclusion Via endoplasmic reticulun stress signaling pathways may be one of the mechanism of Atorvastatin in protection of myocardium in ischemia/ reperfusion injury.