【作者】 郭津； 徐长庆； 李鸿珠； 王丽娜； 张伟华； 李光伟； 赵雅君； 张力； 田野；

【Author】 Jin Guo Changqing Xu Hongzhu Li Lina Wang We-hua Zang Li Guang-wei1 ZHAO Ya-jun1 ZHANG Li1 TIAN Ye1 Department of Pathophysiology,Harbin Medical University150086,Biopharm aceutical Key Laboratory of Heilongjiang Province,Harbin 150086,China.

【机构】 哈尔滨医科大学病理生理教研室； 黑龙江生物医药工程重点实验室；

【摘要】 目的:观察钙敏感受体在动脉粥样硬化大鼠心肌的表达变化及其对心肌梗死敏感性的影响。方法:采用高脂饮食和注射VD3的方法,复制大鼠高脂血症和动脉粥样硬化模型,异丙肾上腺素(200mg/kg)皮下注射制备大鼠心肌梗死模型。Wistar大鼠随机分为6组:正常对照组(Control):动脉硬化组(AS):异丙肾上腺素1d和2d组(ISO/Id,ISO/2d);动脉硬化+异丙肾上腺素1d和2d组(AS+ISO/Id,AS+ISO/2d)(n=12)。采用RT-PCR和Western blot分别检测CaSK、Bax、Bcl-2、caspase-3、Fas的mRNA和蛋白表达;TUNEL染色观察心肌细胞凋亡情况;光镜观察腹主动脉形态学变化;光镜和电镜观察心肌形态学和超微结构变化:紫外分光法检测乳酸脱氢酶(LDH)、肌酸激酶(CK)、超氧化物岐化酶(SOD)的活性和丙二醛(MDA)的含量,电化学免疫发光法检测肌钙蛋白(cTnT)水平。结果:与Control组比较,ISO/1d组:LDH和CK活性、MDA含量和cTnT水平、细胞凋亡指数以及CaSR、Bax、caspase-3和Fas的表达均升高,同时SOD活性降低,Bcl-2表达减少,心肌细胞超微结构损伤严重;与ISO/1d组比较,lSO/2d组,上述变化有所减轻,AS+ISO/1d组则进一步加重。结论:动脉粥样硬化大鼠心肌钙敏感受体的表达增加可增加对心肌梗死的敏感性,其机制与氧化应激损伤和细胞凋亡加重有关。更多还原

【Abstract】 Objective;To observe the expression changes of calcium-sensing receptor in atherosclerosis rat and its influence on sensitivity to myocardial infarction.Methods;The rat hyperlipoidemia and artherosclerosis(AS) models were reproduced using high cholesterol diet and intraperitoneal injection of VD3 (6×105U/kg).The rat myocardial infarction models were prepared by subcutaneous injection ofisoprei(ISO,200mg.kg-1.d-1 for 2 days).Wistar rats were divided randomly into six groups:①Control group;②ISO/Id group;③ISO/2d group;④AS group;⑤arteriosclerosis+ ISO/ld group (AS+ISO/ld group);⑥AS+ISO/2d group (n=12).The expressions ofCaSR,Bcl-2,Bax and caspase-3 were analyzed using Western blot and RT-PCR.Apoptotic c,ells were measured by TUNEL staining assay.The morphological and ultrastructural changes were observed under optical microscope and electromicroscope.The activity of LDH,CK,SOD and the content of MDA were assayed with ultraviolet spectrophotometer.The level ofcTnT was observed by chemical immunofluoresence.Results;Compared with Control group,the activity of LDH and CK,the content of MDA and cTnT,the apoptosis index and the expression ofCaSR,Bax and caspase-3 were increased but the SOD activity and Bcl-2 expression were decreased,the myocardial ultrastructure injury was aggravated in the ISO/ld group;Compared with ISO/ld group,above-mentioned changes were lightened in the ISO/2d group,but was further aggravated in the AS+ISO/1d group.Conclusion;The increased expression of CaSR in rat with artherosclerosis can induce the increase of sensitivity to myocardial infarction,which mechanism is related with further aggravation of oxidative stress injury and apoptosis.更多还原