甲羟戊酸途径中关键酶在肺动脉高压大鼠肺动脉组织中的表达变化

发布时间：2018-09-12 15:48

【摘要】：背景:肺动脉高压(PAH)是一种严重的肺血管疾病。肺动脉高压的定义是指平均肺动脉压大于25mmHg。肺动脉高压的病理特征是远端肺动脉内膜增生、丛状病变、肌肉梗死和血栓形成逐渐发展成腔的闭塞,肺动脉压持续增高并最终导致右心衰竭。以前的研究发现甲羟戊酸途径在心血管重塑中起重要作用。然而,甲羟戊酸途径是否参与肺动脉高压疾病的发生和发展仍然是未知。本研究旨在研究甲基戊酸途径中的关键酶在野百合碱(MCT)诱导的肺动脉高压疾病模型中的表达是否发生了变化。方法:F344大鼠随机分成两组(每组6只):对照组按大鼠体重一次性腹腔注射生理盐水;MCT诱导造模组按体重一次性腹腔注射MCT(60mg/kg)。正常喂养4周后,测量大鼠右心室收缩压,收集大鼠肺动脉和肺组织,检测甲羟戊酸途径中相关酶和下游因子在肺动脉中的表达。结果:在本研究中,我们检测到了包括FDPS、FNTA和GGTase-I在内的甲羟戊酸途径中关键酶的表达量在肺动脉高压中发生了显著增加。同时,小G蛋白RhoA和Racl的表达量也上调了,其下游因子ROS和NADPH的活性增加,eNOS和血清中NO的量下调。结论:在肺动脉高压中FDPS、FNTA和GGTase-I的表达量发生了变化,暗示着甲羟戊酸途径参与了肺动脉高压的病理发展。这种机制可能是通过调节小G蛋白实现的。这些结果可能会为肺动脉高压的治疗提供潜在的药物作用靶点。
[Abstract]:Background: pulmonary hypertension (PAH) is a severe pulmonary vascular disease. Pulmonary hypertension is defined as the mean pulmonary artery pressure greater than 25 mm Hg. The pathological features of pulmonary hypertension are hyperplasia of the distal pulmonary artery intima, plexiform lesions, muscle infarction and thrombosis gradually develop into lumen occlusion, pulmonary artery pressure continues to increase and eventually lead to right heart failure. Previous studies have found that the mevalic acid pathway plays an important role in cardiovascular remodeling. However, whether mevalic acid pathway is involved in the development of pulmonary hypertension is still unknown. The purpose of this study was to investigate whether the expression of key enzymes in methylvalerate pathway has changed in the model of pulmonary hypertension induced by monocrotaline (MCT). Methods Twenty F344 rats were randomly divided into two groups (6 rats in each group): the control group (n = 6) was treated with intraperitoneal injection of MCT (60mg/kg). After 4 weeks of normal feeding, the systolic blood pressure of right ventricle was measured, pulmonary artery and lung tissues were collected, and the expression of related enzymes and downstream factors in pulmonary artery were detected. Results: in this study, we detected a significant increase in the expression of key enzymes in the mevallic acid pathway, including FDPS,FNTA and GGTase-I, in pulmonary hypertension. At the same time, the expression of small G protein RhoA and Racl was up-regulated, and the activities of ROS and NADPH, the downstream factors, increased the activity of Enos and down-regulated the amount of NO in serum. Conclusion: the expression of FDPS,FNTA and GGTase-I changes in pulmonary hypertension, suggesting that mevalerate pathway is involved in the pathological development of pulmonary hypertension. This mechanism may be achieved by regulating small G protein. These results may provide potential drug targets for the treatment of pulmonary hypertension.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.1

【相似文献】