人参皂苷Re通过TRPC介导的钙信号通路改善自发性高血压大鼠左心室肥厚

Ginsenoside Re improves left ventricular hypertrophy of spontaneously hypertensive rats via TRPC mediated calcium signaling pathway

目的研究人参皂苷Re(GS-Re)对自发性高血压大鼠(SHR)左心室肥厚(LVH)的改善作用,并进一步研究其机制是否与经典瞬时受体电位通道(TRPC)介导的钙信号通路相关。方法将14周龄雄性SHR随机分为SHR模型组、GS-Re 10组(10 mg/kg),GS-Re 20组(20 mg/kg),GS-Re 40组(40 mg/kg)和卡托普利组(30 mg/kg),以同龄雄性京都Wistar大鼠(WKY)作为对照组。给药组每日灌胃1次,SHR组和WKY组给予等体积的双蒸水。每周检测大鼠收缩压,给药12周后使用小动物超声检测仪检测大鼠左心室结构。计算大鼠心脏质量指数和左心室肥厚指数。H&E和Masson染色观察大鼠左心室心肌形态。利用Western blot检测大鼠左心室组织中TPRC1、TRPC3、TRPC6、CaN和CaMKⅡδ蛋白的表达。结果与对照组比较,模型组大鼠收缩压、校正左心室质量、舒张末期左心室前壁和后壁厚度、心脏质量指数、左心室肥厚指数、心肌细胞横截面积和胶原纤维沉积明显升高(P<0.05);左心室TPRC1、TRPC3、TRPC6、CaN和CaMKⅡδ蛋白表达也明显升高(P<0.05)。与模型组比较,给予GS-Re后,各组大鼠收缩压、舒张末期前壁和后壁厚度、心脏质量指数、左心室肥厚指数、左心室心肌细胞横截面积和胶原纤维沉积随GS-Re剂量增加而降低(P<0.05);TPRC1、TRPC3、TRPC6、CaN和CaMKⅡδ蛋白表达随GS-Re剂量增加而下降(P<0.05)。结论GS-Re能够改善SHR的左心室肥厚,其作用机制与抑制TRPC及其介导的钙信号通路相关。

Objective To investigate effects of ginsenoside Re(GS-Re)on left ventricular hypertrophy in spontaneously hypertensive rats(SHR)and its possible mechanism related to the regulation of the transient receptor potential canonical channel(TRPC)-mediated calcium signaling pathway.Methods The 14 week age male SHR were randomly divided into model group(SHR group),GS-Re10 group(10 mg/kg),GS-Re20 group(20 mg/kg),GS-Re40 group(40 mg/kg)and Captopril group(30 mg/kg).Male Wistar Kyotorats(WKY)of the same age as control group.The medication administration group were given once daily by gavage and equal volumes of double distilled water were given to the SHR and WKY groups for a total of 12 weeks of treatment.Systolic blood pressure was measured weekly in each group of rats.After 12 weeks of administration,left ventricular structure were measured by animal ultrasound imaging system.Then calculate the heart mass index and left ventricular hypertrophy index.The morphology of the left ventricular myocardium of each group of rats was examined by H&E staining and Masson staining.The protein expression of TRPC1,TRPC3,TRPC6,CaN and CaMKIIδin the left ventricular of each group of rats was detected using Western blot.Results Compared with the WKY group,systolic blood pressure,the left ventricular mass cor,the end-diastolic anterior and posterior wall thickness,heart mass index,left ventricular hypertrophy index,cardiomyocyte cross sectional area and collagen volume were significantly higher in the SHR group.Systolic blood pressure,end-diastolic anterior and posterior wall thickness,cardiac weight index,left ventricular hypertrophy index,myocardial cell cross-sectional area and collagen deposition were significantly higher in the SHR group compared with the control group(P<0.05).The protein expression of TRPC1,TRPC3,TRPC6,CaN and CaMKIIδwere up-regulated in SHR group.Compared with the model group,systolic blood pressure,end-diastolic anterior and posterior wall thickness,heart mass index,left ventricular hypertrophy index,left ventricular cardiomyocyte cross sectional area and collagen volume were reduced in rats after GS-Re administration(P<0.05).The protein expressions of TRPC1,TRPC3,TRPC6,CaN and CaMKIIδwere down-regulated(P<0.05).Conclusion GS-Re can improve left ventricular hypertrophy in SHR,the effect may be related to inhibiting the TRPC-mediated calcium signaling pathway.