三味檀香散改善高原肺动脉高压大鼠右心室重构的作用

Effect of Sanwei Tanxiang powder on the alleviating right ventricular remodeling in rats of high altitude pulmonary hypertension

目的研究三味檀香散改善高原肺动脉高压(HAPH)大鼠右心室重构的作用,及该作用与血管紧张素Ⅱ(AngⅡ)及其相关因子表达的关系。方法将SD大鼠随机分为对照组、模型组、三味檀香散高、中、低剂量组,除对照组外,将其余4组大鼠置于低压氧舱内(模拟海拔5 km的高原环境)饲养4周,构建HAPH及右心室重构大鼠模型。采用酶联免疫法测定各组大鼠心肌组织中AngⅡ和内皮素1(ET-1)的含量,采用硝酸还原酶法测定一氧化氮(NO)的含量;采用免疫组化染色法观察右心室组织中AngⅡ和ET-1蛋白的表达情况,并用透射电镜观察右心室心肌组织超微结构的变化。结果与对照组比较,模型组大鼠心肌组织中AngⅡ和ET-1的含量升高,NO的含量降低;右心室中AngⅡ和ET-1蛋白的表达量明显增加;右心室的心肌线粒体肿胀,嵴部分断裂溶解,部分空泡变性,间质胶原纤维重度增生。与模型组比较,三味檀香散预处理组大鼠心肌组织中AngⅡ及ET-1的含量均明显降低,NO的含量明显升高;大鼠右心室中AngⅡ和ET-1蛋白的表达明显减少;心肌线粒体超微结构的损伤有所改善。结论三味檀香散改善HAPH大鼠右心室重构的作用与减少大鼠心肌组织中AngⅡ和ET-1的含量,提高NO的含量、下调右心室中AngⅡ和ET-1蛋白的表达水平及保护心肌右心室线粒体的结构有关。

OBJECTIVE To study Sanwei Tanxiang powder on the role of AngⅡ and relative factors in alleviating right ventricular remodeling in rats of high altitude pulmonary hypertension. METHODS The SD rats were divided into the control group, model group, high, middle and low does of Sanwei Tanxiang groups. The rats of other groups were kept in hypobaric chamber which simulated the hypoxic environment of a 5 km altitude for four weeks in order to establish the high altitude pulmonary hypertension and right ventricular remodeling animal model, expecting the rats of control group. The enzyme - linked immunosorbent assay was used to detect Ang Ⅱ and entothelin 1 （ ET - 1 ） contents in cardiac homogenate. The content of nitric oxide （NO） was detected by nitric oxide assay kit. The immunohistochemistry was used to analyze the expression level of Ang Ⅱ and ET - 1 in right ventricular. The TEM was used to observe the uhrastructural change in right ventrieular. RESULTS Compared with the control group,the contents of Ang Ⅱ and ET - 1 in cardiac muscles of the model group were increased and the content of NO was decreased significantly. The expression levels of Ang Ⅱ and ET - 1 were increased and the changes of myocardial mitochondria in right ventricle, such as swelling, breakage of mitochondria ridge, vacuolar degeneration and hyperplasia of interstitial collagen were observed. Compared with the model group, after the intervention of Sanwei Tanxiang powder, the contents of Ang Ⅱ and ET - 1 were decreased and the content of NOwas increased significantly. The expression levels of Ang Ⅱ and ET - 1 were decreased and uhrastructural damage was alleviated in right ventricle. CONCLUSION Right ventricular remodeling that is alleviated by Sanwei Tanxiang powder in rats of high altitude puhnonary hypertension was based on mechanisms as follows ： Decreasing the content of Ang Ⅱ and ET - 1, increasing the content of NO in cardiac muscle, down - regulating the expression level of Ang Ⅱ and ET - 1 and protecting mitoehondrial ultrastructure in right ventricle.