摘要
观察动脉粥样硬化对大鼠心肌钙敏感受体(CaSR)表达和MAPK通路的影响。采用腹腔注射维生素D3(VitD3,6×105U/kg)+高脂饮食6周的方法,建立大鼠动脉粥样硬化模型。Wistar大鼠随机分为正常对照组(n=12)和动脉粥样硬化组(n=12)。采用Western blot观察大鼠心肌CaSR、p-ERK、p-JNK和p-P38的蛋白表达;TUNEL染色观察心肌细胞凋亡情况;光镜观察腹主动脉和心肌形态学变化;电镜观察心脏超微结构变化;紫外分光法检测血清肌酸激酶(CK)、超氧化物岐化酶(SOD)的活性和丙二醛(MDA)含量,电化学免疫发光法检测肌钙蛋白T(cTnT)水平。与正常对照组相比,动脉粥样硬化组的CK活性、MDA含量、cTnT水平、细胞凋亡指数以及CaSR、p-ERK、p-JNK和p-P38的表达均明显升高,而SOD活性则显著降低,心肌细胞超微结构损伤严重。动脉粥样硬化性心肌损伤可能与氧化应激使心肌CaSR表达增加,进而通过MAPK通路激活诱导细胞凋亡有关。
To observe effect of artherosclerosis on expression of calcium-sensing receptor（CaSR） and MAPK pathway in rat myocardium.The rat artherosclerosis models were prepared using intraperitoneal injection of VitD3（6×105 U/kg） with high cholesterol diet for 6 weeks.Wistar rats were divided into two groups： control group（n=12） and AS group（n=12）.The expressions of CaSR,p-ERK,p-JNK and p-P38 were analyzed using Western blot.Apoptotic cells were measured by TUNEL staining assay.The morphological changes of abdominal aorta and of cardiac tissues were observed under optical microscope and electromicroscope.The activity of creatine kinase（CK）,superoxide dismutase（SOD） and the content of malondialdehyde（MDA） were assayed with ultraviolet spectrophotometer.The level of cTnT was detected by electrochemical immunofluoresence.And the results showed that compared with control group,the activity of CK,the content of MDA and cTnT,the apoptosis index,the expression of CaSR,p-ERK,p-JNK and p-P38 were increased,but the SOD activity was decreased,the myocardial ultrastructure injury was aggravated in the AS group.Artherosclerosis myocardial injury is likely to relate with the up-regulation of calcium-sensing receptor expression induced by oxidative stress,which results in apoptosis through MAPK pathway activation.
基金
高等学校博士学科点专项科研基金资助项目(20070226012)
国家自然科学基金资助项目(30871012
30470688
81000059
30700288)
黑龙江省卫生厅科研课题资助项目(2009-214)
哈尔滨医科大学研究生创新基金资助项目(HCXB2008006)
黑龙江省研究生创新科研资金资助项目(YJSCX2008-106HLJ)
关键词
动脉粥样硬化
钙敏感受体
心肌
细胞凋亡
atherosclerosis
calcium-sensing receptors
myocardium
apoptosis
