【摘要】 目的检测阿霉素(doxorubicin,DOX)诱导大鼠心肌损伤过程中心肌钙敏感受体(calcium-sensing receptor,CaSR)表达水平的变化,初步探讨钙敏感受体在心肌损伤中的作用。方法雄性Wistar大鼠40只,随机分为对照组(n=10)和损伤组(n=30),损伤组大鼠分为3周组、6周组和9周组。采用腹腔注射阿霉素(2.5mg.kg-1.w-1)诱导大鼠心肌损伤。应用超声心动图检测各组大鼠左心室内径以及功能。取大鼠心肌组织,HE染色观察大鼠心肌形态和结构的变化。Western blot和免疫组化法检测CaSR蛋白的表达。结果①与对照组相比,9周组大鼠左室舒张末期内径(LVDD)增加(P<0.05),左室射血分数(LVEF)明显降低(P<0.01);②HE染色显示对照组心肌细胞形态正常,损伤组心肌出现细胞肿胀,胞浆疏松淡染、嗜酸性增强,细胞核增大,横纹不清及空泡样变性;③阿霉素作用3周后CaSR表达明显降低(P<0.01)。6周组与3周组比较无显著性差异。9周组与对照组无明显差异,但明显高于3周组和6周组(P<0.01)。结论在DOX诱导大鼠心肌损伤过程中,CaSR表达先降低后升高,这可能为临床治疗阿霉素引起的心肌损伤提供药物作用靶点及对心肌损伤和心功能降低的判定具有一定意义。更多还原

【Abstract】 Objective To detect the expression of calcium-sensing receptor(CaSR) during development of myocardial injury,to provide new ideas for the role of CaSR in the process of myocardial injury induced by doxorubicin.Methods Forty male Wistar rats were randomly divided into two groups: control group(n=10) and injury group(n=30).The injury group rats were randomly divided into 3 weeks group,6 weeks group,and 9 weeks group.Myocardial injury was induced by intraperitoneal injection of doxorubicin(2.5 mg·kg-1·w-1).Left ventricular internal diameter and the cardiac function of the rats in each group were detect by echocardiography.The myocardial histologic structural changes were observed under the microscope after HE staining.Futher more the expression of CaSR was analyzed by Western blot and immunohistochemistry.Results The left ventricular end diastolic diameter(LVDD) was increased obviously in 9 weeks group compared with control group(P<0.05),and the left ventricular ejection fraction(LVEF) reduced significantly(P<0.01).HE staining showed that the cellular morphology of the control group was normal,while the cell swell,cytoplasm loose and lightly stained,eosinophilic enhanced,nuclei enlarged,unclear stripes and vacuolar degeneration in the myocardial injury group.The quantitative expression of CaSR was significantly decreased in the first three weeks after treatment of doxorubicin while increased at 9 weeks(P<0.01),There was no significant difference between the group of 3 weeks and 6 weeks.Conclusion The change in expression of CaSR during the process of myocardial injury is firstly decrease and then increase,which may provide a new treatment for the myocardial injury induced by doxorubicin.The change of CaSR may play an important role in determining the severity of myocardial injury and heart function.更多还原