【摘要】：背景:肺動脈高壓(PAH)是一種嚴重的肺血管疾病。肺動脈高壓的定義是指平均肺動脈壓大于25mmHg。肺動脈高壓的病理特征是遠端肺動脈內(nèi)膜增生、叢狀病變、肌肉梗死和血栓形成逐漸發(fā)展成腔的閉塞,肺動脈壓持續(xù)增高并最終導(dǎo)致右心衰竭。以前的研究發(fā)現(xiàn)甲羥戊酸途徑在心血管重塑中起重要作用。然而,甲羥戊酸途徑是否參與肺動脈高壓疾病的發(fā)生和發(fā)展仍然是未知。本研究旨在研究甲基戊酸途徑中的關(guān)鍵酶在野百合堿(MCT)誘導(dǎo)的肺動脈高壓疾病模型中的表達是否發(fā)生了變化。方法:F344大鼠隨機分成兩組(每組6只):對照組按大鼠體重一次性腹腔注射生理鹽水;MCT誘導(dǎo)造模組按體重一次性腹腔注射MCT(60mg/kg)。正常喂養(yǎng)4周后,測量大鼠右心室收縮壓,收集大鼠肺動脈和肺組織,檢測甲羥戊酸途徑中相關(guān)酶和下游因子在肺動脈中的表達。結(jié)果:在本研究中,我們檢測到了包括FDPS、FNTA和GGTase-I在內(nèi)的甲羥戊酸途徑中關(guān)鍵酶的表達量在肺動脈高壓中發(fā)生了顯著增加。同時,小G蛋白RhoA和Racl的表達量也上調(diào)了,其下游因子ROS和NADPH的活性增加,eNOS和血清中NO的量下調(diào)。結(jié)論:在肺動脈高壓中FDPS、FNTA和GGTase-I的表達量發(fā)生了變化,暗示著甲羥戊酸途徑參與了肺動脈高壓的病理發(fā)展。這種機制可能是通過調(diào)節(jié)小G蛋白實現(xiàn)的。這些結(jié)果可能會為肺動脈高壓的治療提供潛在的藥物作用靶點。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R544.1

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