摘要
目的:通过腹主动脉缩窄所致心肌肥厚模型,探讨丹参酮的抗心室重构与钙调神经磷酸酶信号通路的关系。方法:SD大鼠通过腹主动脉缩窄建立高血压的心肌肥厚模型,4周后将手术大鼠分为手术组(B组),丹参酮低剂量组[C组,10 mg/(kg.d)],丹参酮高剂量组[D组,20 mg/(kg.d)]及缬沙坦组[E组,10 mg/(kg.d)],每组各8只,另有8只SD大鼠作为假手术组(A组)。用药8周后检测各组尾动脉压,取左心室组织检测左心室质量指数(LVMI),病理切片HE染色测量心肌纤维直径(MFD),采用逆转录-聚合酶链式反应法检测AT1受体mRNA表达,采用免疫印迹法检测AT1受体和CaN的蛋白表达,通过Fura-2双波长荧光法检测心肌细胞内游离Ca2+浓度。结果:与A组和E组比较,B、C、D组的血压值显著升高,差异有高度统计学意义(P<0.01),B、C、D组间血压差异无统计学意义(P>0.05)。C、D、E组的LVMI、MFD值均高于A组,且显著低于B组,差异均有统计学意义(P<0.05)。与其他各组相比,AT1受体蛋白和mRNA水平在B组中表达最高,差异有高度统计学意义(P<0.01),而C、D组间表达差异无统计学意义(P<0.05),但均高于E组,差异有统计学意义(P<0.05),C、D、E组的AT1受体mRNA表达水平均未降至A组水平,差异有统计学意义(P<0.05)。B组的CaN蛋白表达水平较其他各组明显升高,差异有统计学意义(P<0.05),且丹参酮对其表达的干预呈剂量依赖性,D、E组间CaN蛋白表达差异无统计学意义(P>0.05)。B组细胞内Ca2+浓度明显高于其他各组,差异有高度统计学意义(P<0.01),但D、A组间差异无统计学意义(P>0.05),E、C组Ca2+浓度均高于A、D组,差异有高度统计学意义(P<0.05)。结论:丹参酮可通过阻止心肌细胞的钙离子内流,减少钙调神经磷酸酶的表达,起到抑制心肌肥厚的作用。
Objective： To explore the relationship between Tanshinone resistance left ventricular remodeling and calcineurin signal pathway by the rat models of myocardial hypertrophy which were caused by abdominal aortic coarctation.Methods： SD rats were operated with abdominal aorta constriction to construct the model of myocardial hypertrophy.After 4 weeks,model rats were divided into four groups： artificial operation group（group B）,low dose Tanshinone group [group C,10 mg/（kg·d）],high dose Tanshinone group [group D,20mg/（kg·d）] and Valsartan group [group E,10mg/（kg·d）],each of 8 cases and 8 rats were divided into sham operation group（group A）.8 weeks later,tail arterial pressure and the left ventricular mass index（LVMI） were measured,and myocardial fiber dimension（MFD） which were stained with HE reagent also was measured.AT1 receptor mRNA expression was detected by RT-PCR.AT1 receptor and CaN protein expression were detected by western blotting in left ventricular tissues of all groups.i was observed by Fura-2 double wavelengths fluorescence method.Results： The blood pressure in group B,C,D were obviously higher than that in group A and group E,the difference was statistically significant（P0.01）,But there was no statistical difference between group B,C and D（P0.05）.The LVMI and MFD vaule were obviously higher in group C,D,E than that of group A,and lower than that of group B,the differences were statistically significant（P0.05）.The protein and mRNA expression of AT1 receptor in group B were the highest in all groups,the differences were statistically significant（P0.01）,and there was no statistical different between group C and D（P0.05）,which was higher than group E,the difference was statistically significant（P0.05）.But the mRNA expression in group C,D and E were not recovered to the normal level（group A）,the differences were statistically significant（P0.05）.The protein expression of CaN in group B was obviously higher than that of other groups,the di
出处
《中国医药导报》
CAS
2011年第29期18-21,共4页
China Medical Herald
基金
国家自然科学基金资助项目(项目编号:30500657)
