摘要:
Objective To explore the effects and mechanisms of tanshinone Ⅱ A (Tan Ⅱ A) on cardiac hypertrophy in rats.Methods 40 SD rats of 2-3 months old were randomly divided into four groups with 10 in each group,transverse aortic constriction (TAC) was used to simulate pressure-overload models.The four groups were handled as follows,the sham group rats just underwent laparotomy;the surgery group were exposed to TAC as TAC group;the Tan Ⅱ A group rats were administered Tan Ⅱ A (20 mg· kg-1· d-1) by intraperitoneal injection for 8 weeks after TAC;the negative control group rats were given normal saline (20 mg· kg-1 · d-1) by intraperitoneal injection for 8 weeks after TAC.After 8 weeks of TAC,we randomly chose 6 rats from each group and anaesthetized them.Echocardiogram was performed to evaluate cardiac structure and function.After measuring body weight,the chosen rats were dissected and their heart weight were measured to calculate heart-weight index (HWI).The acquired heart tissue was used to produce frozen sections performed with hematoxylin and eosin (HE) staining and Masson staining to evaluate cell surface area (CSA) and collagen volume fraction (CVF),respectively.Western blot analysis was performed to evaluate calcium/calmodulin-dependent protein kinase Ⅱ (CAMK Ⅱ) and calcineurin (CAN) protein expression in rat heart tissue.Results Compared to TAC group,Tan Ⅱ A group rats had lower left ventricular posterior wall thickness (LVPWd) and interventricular septum thickness (IVSd) [LVPWd:(0.2± 0.01) cm vs (0.22±0.01) cm,P<0.05;IVSd:(0.18±0.02) cm vs (0.22±0.02) cm,P<0.05].HWI was also lower in Tan Ⅱ A group compared with TAC group [(43.43:±5.10) mg/g vs (49.38±3.80) mg/g,P<0.05].The staining results showed Tan Ⅱ A significantly inhibited myocardial hypertrophy and fibrosis caused by TAC[CSA:(555.48±879.81) μm2 vs (514.74± 1281.16) μm2,P<0.05;CVF:(8.63%±2.26% vs 12.39%± 1.90%,P<0.05)].Western blot analysis demonstrated that Tan Ⅱ A could reduce the elevation of CAMK Ⅱ and CaN protein expression resulted from TAC[CAMK Ⅱ:(1.2±0.1) vs (1.83±0.25),P<0.05;CaN:(1.27±0.12) vs (1.93±0.49),P<0.05].Conclusion Tanshinone Ⅱ A could inhibit pressure-overload induced myocardial hypertrophy in rats.%目的 研究丹参酮ⅡA对大鼠心肌肥厚的影响及相关机制.方法 将40只2~3月龄的SD大鼠随机分为4组,每组10只.应用腹主动脉缩窄术(TAC)制造压力负荷模型.4组大鼠分别做如下处理:对假手术组只开腹不作特殊处理;对手术处理组行TAC(TAC组);对丹参酮ⅡA干预组行TAC后,给予腹腔注射丹参酮ⅡA8周(20 mg· kg-1·d-1);对阴性对照组行TAC后,给予腹腔注射生理盐水8周(20 mg℉kg-1·d-1).8周后从各组随机选取6只小鼠,对小鼠麻醉后行超声心动图检查评估心脏结构和功能;测量小鼠体重后进行心脏取材,测量心脏重量,计算大鼠心脏重量指数(HWI);制作心肌组织切片,进行苏木精-伊红染色(HE)和Masson染色,检测心肌细胞横切面积(CSA)以及胶原体积分数(CVF);用免疫印迹法检测心肌组织钙调蛋白激酶Ⅱ(CAMKⅡ)和钙调神经磷酸酶(CAN)的蛋白表达水平.结果 对比TAC组,丹参酮ⅡA组大鼠左心室后壁舒张末厚度(LVPWd)和室间隔舒张末厚度(IVSd)均显著下降[LVPWd:(0.2±0.01)cm比(0.22±0.01) cm,P<0.05;IVSd:(0.18±0.02) cm比(0.22±0.02) cm,P<0.05],HWI下降[(43.43±5.1) mg/g比(49.38±3.8) mg/g,P<0.05];组织染色结果显示,丹参酮ⅡA干预组显著降低了TAC引起的CSA和CVF升高[CSA:(555.48±879.81) μm2比(514.74±1 281.16) μm2,P<0,05;CVF:(8.63%±2.26%比12.39%±1.9%,P<0.05)];免疫印迹法结果提示,丹参酮ⅡA组大鼠较TAC组心肌组织内CAMKⅡ和CaN的蛋白表达量显著下降[CAMKⅡ:(1.2±0.1)比(1.83±0.25),P<0.05;CAN:(1.27±0.12)比(1.93±0.49),P<0.05].结论 丹参酮ⅡA能抑制压力负荷引起的心肌肥厚.