黄芩苷对肾性高血压大鼠血压及抑制左心室重构的作用

Effects of Baicalin on blood pressure and left ventricular remodeling in rats with renal hypertension

目的探索黄芩苷对肾性高血压大鼠血压及抑制左心室重构的作用。方法雄性Wistar大鼠40只,随机抽取10只为假手术组,其余采用两肾一夹法造成肾性高血压大鼠模型,6周后将造模成功大鼠随机分为模型组和黄芩苷组,最终存活大鼠假手术组(n=9)、模型组(n=10)及黄芩苷组(n=11),连续给药4周。观察大鼠的一般情况,分别于造模前、造模6周后及给药4周后检测各组大鼠血压变化;给药4周后各组大鼠行高频超声心动图检查,测定各项心功能指标;处死大鼠,取心脏,行HE、Masson染色。用TUNEL法检测各组大鼠心肌细胞凋亡;real-time PCR检测各组大鼠心肌细胞葡萄糖调节蛋白78(GRP78)、葡萄糖调节蛋白94(GRP94)表达;Western blot检测各组大鼠心肌细胞内质网伴侣蛋白GRP78、GRP94及CCAAT增强子结合蛋白同源蛋白(CHOP)、Caspase 3表达。结果与模型组相比,黄芩苷组大鼠治疗后血压下降(P<0.05),心脏彩超结果显示左心室重构各项指标均有明显改善(P<0.05)。与模型组相比,黄芩苷组大鼠心肌纤维化病理积分及纤维化相关因子基质金属蛋白酶9(MMP-9)、基质金属蛋白酶2(MMP-2)、结缔组织生长因子(CTGF)和转化生长因子(TGF-β1)表达明显下降(P<0.05)。与模型组相比,黄芩苷组大鼠心肌组织GRP78、GRP94、CHOP及Caspase 3表达及细胞凋亡明显减少(P<0.05)。结论黄芩苷具有一定降压作用,可改善肾性高血压大鼠左心室重构,减轻心肌病理变化,缓解内质网应激,减少心肌细胞凋亡。

Aim To explore the effect of Baicalin on blood pressure and left ventricular remodeling in rats with renal hypertension. Methods Amogn 40 male Wistar rats 10 were randomly selected for sham operation group, which renal hypertensive rat model was established by using two kidney one clip method. The rats with renal hypertension were randomly divided into model group and Baicalin group after 6 weeks, eventually alive rats were devided into sham operation group （ n = 9）, model group （ n = 10） and Baicalin group （ n = 11 ） for 4 weeks intervention. During the experiment, the general situation of rats was observed, and the blood pressure were detected before operation, operation after 6 weeks, and intervention for 4 weeks ; high frequency echocardiography were detected after 4 weeks and the cardiac function indexes were measured. The rats were sacrificed and the heart was removed. The morphological changes of myocardial tissue was observed by using HE staining, Masson staining. The myocardial apoptosis was detected by TUNEL method and the expression of endoplasmic reticulum chaperone glucose regulated protein （ GRP78 ） , glucose regulated protein （ GRP94 ） in myocardial cell of rats were also detected by real-time PCR and Western blot. The expression of CCAAT/enhancer binding protein homologous protein（CHOP） and Caspase 3 was monitored by Western blot. Results Compared with model group, there was significant change of blood pressure in Baicalin group （P〈0.05）, and the indexes of left ventricular remodeling were significantly improved after the echoeardiography （P〈 0.05 ）. Compared with model group, the integral of pathological myocardial fibrosis and fibrosis related factors matrix metalloprotein-9 （MMP-9）, matrix metalloprotein-2 （MMP-2） , connective tissue growth factor（CTGF） and transforming growth factor-β1 （TGF-β1） expression was significantly decreased in Baicalin group（P〈0.05）. Compared with model group, the expression of GRP78, GRP94, CHOP, Caspase 3 and apoptosis of cardiomyocyte were significantly decreased in Baicalin group（P〈O.05）. Conclusion Baicalin had a certain antihypertensive effect, it could improve the left ventricular remodeling in renal hypertensive rats, reduce myocardial pathological changes, ease the endoplasmic reticulum stress and reduce apoptosis in myocardial cell.