丹参酮ⅡA对压力超负荷大鼠心肌肥厚及MAPK通路的影响  

Effects of Sodium Tanshinone ⅡA Sulfonate on Cardiac Hypertrophy and MAPK Signaling Pathway

作　　者：周亚光[1] 屠恩远[1] 王照华[1] 梁黔生[1] 杨光田[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院急诊科,武汉430030

出　　处：《华中科技大学学报（医学版）》2010年第1期29-32,36,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30500657)

摘　　要：目的探讨丹参酮ⅡA对大鼠胸主动脉缩窄诱导的心肌肥厚及丝裂原活化蛋白激酶(MAPK)信号转导通路的影响。方法通过在右无名动脉和左侧颈总动脉之间部分缩窄胸主动脉而诱导大鼠心肌肥厚模型。将制好的模型大鼠随机分成6组:假手术组、胸主动脉缩窄组、胸主动脉缩窄组+低剂量丹参酮组(5 mg/kg)、胸主动脉缩窄组+中剂量丹参酮组(10 mg/kg)、胸主动脉缩窄组+高剂量丹参酮组(20 mg/kg)、胸主动脉缩窄组+缬沙坦组(10 mg/kg)。用药8周后,B超检测心肌肥厚程度和心功能的变化;将心肌样本沿横切面切开并做苏木精-伊红染色;Western blot法分析心肌MAPK信号蛋白表达变化。结果胸主动脉缩窄组相对于假手术组在心脏重量指数、左室重量指数、心肌纤维直径、左心室后壁及室间隔厚度均增加。而丹参酮ⅡA和缬沙坦组均可减轻上述变化的程度。Western blot结果显示:相对假手术组,模型组的p-ERK(磷酸化的细胞外信号调节激酶)和p-p38(磷酸化的p38丝裂原活化蛋白激酶)均减少,差异均具有统计学意义(均P<0.01)。相对于模型组,各丹参酮ⅡA和缬沙坦治疗组p-ERK减少,差异均具有统计学意义(均P<0.05);丹参酮ⅡA高剂量和中剂量组,以及缬沙坦治疗组p-p38增加,差异均具有统计学意义(均P<0.05)。结论丹参酮ⅡA通过调节MAPK通路中的蛋白表达而发挥其抑制心肌肥厚的作用。Objective To determinate the effects of sodium tanshinone ⅡA sulfonate（STS）on cardiomyocyte hypertrophy and explore the relative effects of STS on mitogen-activated protein kinase signal transduction system in rats with eardiomyocyte hypertrophy through constricting the thoracic aorta. Methods The models of cardiomyocyte hypertrophy were established in vivo ,and the thoracic aorta was partially tied between the right innominate and the left common carotid arteries. The rats were randomly divided into 6 groups（n 8/group）as follows：①sham,②transverse aortic constriction（TAC） ,③TAC-471ow-dose Tan （TAC＋ LT） （5 mg/kg）,④TACq- middle dose Tan（TAC＋MT） （ 10 mg/kg）, ⑤TAC＋high-dose Tan（TAC＋ HT） （ 20 mg/ kg）, and ⑥TAC＋Val（ 10 mg/kg）. After treatment for 8 weeks, echocardiography was performed to observe the changes in hypertrophy and heart function, and heart samples were cut into transverse sections and stained with hematoxylin and eosin （H＆E）. The MAPKs protein expression in the cardiomyocytes was detected by Western blot. Results The heart weight index （HWI）,left ventricular mass index（LVMI）and cross-sectional diameter of cardiomyoeytes（CD）, left ventrieular posterior wall thickness（LVWT）, and interventricular septal thickness （IVS）were significantly increased in TAC group as compared with sham group. The relative parameters in STS groups and Val group were reduced as compared with those in TAC group. Western blot analysis revealed the p ERK and p-p38 expression was significantly decreased in TAC group as compared with sham group （P〈0.01）. The p-ERK expression was significantly decreased in STS groups and Val group as compared with TAC group（P〈0.05）. The TAC＋HT group,TAC＋MT group and Val group had significantly higher p p38 expression than TAC group（P〈0.05）. Conclusion Tanshinone ⅡA could regulate the expression of protein in MAPK pathway to exert its inhibitory effects on hypertrophy of eardiomyocytes.

关 键 词：丹参酮ⅡA 丝裂原活化蛋白激酶 心肌肥厚 胸主动脉缩窄 

分 类 号：R284.1[医药卫生—中药学]