辛伐他汀抑制川畸病大鼠心肌损伤

Simvastatin inhibits myocardial injury in rats induced by Kawasaki disease

目的探讨辛伐他汀对川崎病大鼠心肌的影响及机制。方法随机将SD雄性大鼠分为对照组、模型组及辛伐他汀组,除对照组外其余两组均利用干酪素酸杆菌提取物构建大鼠川崎病心肌损伤模型。心脏超声及组织学切片观察辛伐他汀对大鼠心功能及心肌结构的影响。ELISA试剂盒检测各组血清中心肌损伤指标及心肌组织炎症因子水平。免疫印迹法检测各组心肌组织中凋亡相关蛋白、高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)通路蛋白的表达水平。结果与对照组比较,模型组大鼠心功能指标水平、抗凋亡蛋白B细胞淋巴瘤-2(Bcl-2)表达显著下降,心肌组织炎症细胞浸润增加,炎症因子水平、促凋亡蛋白Bcl-2关联X蛋白及活化的Caspase-3、HMGB1/RAGE通路蛋白表达升高(P<0.05)。与模型组比较,辛伐他汀组以上各个指标均显著逆转(P<0.05)。结论辛伐他汀可抑制川崎病导致的大鼠心肌损伤,其机制可能与抑制HMGB1/RAGE信号通路有关。

Aim To explore the effects and mechanism of simvastatin on the myocardium of rats with Kawasaki disease.Methods SD male rats were randomly divided into control group,model group and simvastatin group,and the rat Kawasaki disease myocardial injury model was constructed by using the extract of Bacillus cereus in the two groups except the control group.The effects of simvastatin on cardiac function and myocardial structure were observed by cardiac ultrasound and histological sections.Serum myocardial injury indicators and levels of inflammatory factors in myocardial tissue in each group were detected by ELISA kits.The expression of apoptosis-related proteins,the high mobility group protein B1(HMGB1)/receptor for advanced glycosylation end products(RAGE)pathway-related proteins were detected by immunoblotting in rat myocardial tissues.Results Compared with the control group,the levels of cardiac function indicators and the expression of anti-apoptotic protein B-cell lymphoma 2(Bcl-2)in the model group significantly were decreased,while the infiltration of inflammatory cells in myocardial tissue were increased,Inflammatory cytokine levels,expression of pro-apoptotic protein Bcl-2 associated X protein and activated Caspase-3,HMGB1/RAGE pathway protein were increased(P<0.05).Compared with the model group,the above indicators in the simvastatin group were significantly reversed(P<0.05).Conclusion Simvastatin can inhibit myocardial damage caused by Kawasaki disease in rats,and its mechanism may be related to the inhibition of the HMGB1/RAGE signaling pathway.