本文關(guān)鍵詞： 肺動(dòng)脈高壓 血流動(dòng)力學(xué) 內(nèi)皮型一氧化氮合酶　出處：《山東大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景：一氧化氮（nitric oxide,NO)是內(nèi)皮細(xì)胞分泌的重要血管活性物質(zhì)，具有擴(kuò)張血管和抑制血管平滑肌細(xì)胞增殖的功能。左旋精氨酸在內(nèi)皮型一氧化氮合酉每（endothelial nitric oxide synthase, eNOS)催化下合成NO，eNOS是該反應(yīng)的限速酶，故eNOS表達(dá)水平高低直接決定內(nèi)皮細(xì)胞NO分泌的多少。左向右分流型先天性心臟�。╟ongenital heatr disease,CHD)的病理生理變化表現(xiàn)為肺循環(huán)血流顯著增多。由于血管內(nèi)皮細(xì)胞附著于血管腔內(nèi)壁，故高肺血流可直接造成肺動(dòng)脈內(nèi)皮細(xì)胞（pulmonary atreiral endothelial cells, PAECs)所受剪切力(shear stress,SS)增加，從而引起PAECs形態(tài)和功能改變。關(guān)于NO在尚肺血流所致肺動(dòng)脈尚壓(pulmonary hypetrension,PH)的過程中的作用目前尚無一致性意見，且多數(shù)實(shí)驗(yàn)研究或?yàn)槁該p傷因素處理的動(dòng)物實(shí)驗(yàn)，或?yàn)橹型砥诓∪耸中g(shù)活檢或死后尸檢病例研究，即多數(shù)研究局限于肺動(dòng)脈高壓慢性或中晚期分子病理事件，而內(nèi)皮細(xì)胞合成分泌的NO及其限速酶eNOS在早期是否受到影響卻鮮有報(bào)道。研究目的：研究流體剪切力對(duì)大鼠PAECs eNOS表達(dá)的影響，探討高肺血流肺動(dòng)脈高壓早期的病理生理變化。研究方法：應(yīng)用體外流室裝置系統(tǒng)，按靜態(tài)組(0dyn/cm2)、低剪切力組(ldyn/cm2)、高剪切力組（3dyn/cm2)對(duì)PAECs施加不同剪切力。RT-PCR法測(cè)定不同剪切力對(duì)PAECs eNOS基因表達(dá)的影響；Westenr blot法檢測(cè)不同剪切力對(duì)PAECs eNOS蛋白表達(dá)的影響。結(jié)果：RT-PCR結(jié)果示，高、低剪切力組eNOS mRNA表達(dá)明顯高于對(duì)照組(p0.05),且剪切力越大eNOS mRNA表達(dá)越高；Western blot結(jié)果示，高、低剪切力組eNOS蛋白表達(dá)水平較對(duì)照組增高（p0.05)，但高剪切力組與低剪切力組之間eNOS蛋白表達(dá)水平差異不顯著。結(jié)論：流體剪切力能夠明顯上調(diào)PAECs eNOS基因及蛋白表達(dá)，，提示eNOS表達(dá)上調(diào)可能在高血流致肺動(dòng)脈高壓形成的早期階段發(fā)揮重要的代償性作用。
[Abstract]:Background: nitric oxide (no) is an important vasoactive substance secreted by endothelial cells. It has the function of dilating blood vessels and inhibiting the proliferation of vascular smooth muscle cells. Endothelial nitric oxide synthase. The synthesis of NON-Enos catalyzed by Enos is the rate-limiting enzyme of this reaction. Therefore, the level of eNOS expression directly determines the amount of no secretion in endothelial cells. Left to right shunt congenital heart disease congenital heatr disease. The pathophysiological changes of CHD were as follows: pulmonary circulatory blood flow was significantly increased, and vascular endothelial cells were attached to the inner wall of vascular cavity. Therefore, high pulmonary blood flow can directly cause pulmonary atreiral endothelial cells in pulmonary endothelial cells. The shear stress of pacs) increased. Therefore, the morphological and functional changes of PAECs were observed. No was found in pulmonary hypetrension of pulmonary artery induced by pulmonary blood flow. There is no consensus on the role of PHs in the process, and most of the experimental studies have been done in animals that deal with chronic injury factors, or in surgical biopsies or postmortem studies of patients in the middle and late stages of the disease. That is, most of the studies are confined to chronic or late molecular pathological events of pulmonary hypertension. However, whether the no and its rate-limiting enzyme eNOS were affected in the early stage of endothelial cells was rarely reported. Objective: to study the effect of fluid shear stress on the expression of PAECs eNOS in rats. To investigate the pathophysiological changes in the early stage of pulmonary hypertension with high pulmonary blood flow. Methods: the external flow chamber system was used according to the static group (0 dyn / cm ~ (2)) and the low shear stress group (n / m ~ (2)). The effect of different shear stress on the expression of PAECs eNOS gene was determined by different shear stress and RT-PCR method in high shear stress group (3 dyn / cm ~ (2)). Westenr blot assay was used to detect the effect of different shear stress on the expression of PAECs eNOS protein. The expression of eNOS mRNA in the low shear stress group was significantly higher than that in the control group, and the higher the shear stress was, the higher the eNOS mRNA expression was. The results of Western blot showed that the expression of eNOS protein in the high and low shear stress groups was higher than that in the control group (p0.05). But there was no significant difference between the high shear stress group and the low shear stress group in the expression of eNOS protein. Conclusion: fluid shear stress can obviously up-regulate the expression of PAECs eNOS gene and protein. The results suggest that the up-regulation of eNOS expression may play an important compensatory role in the early stage of pulmonary hypertension induced by high blood flow.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R725.4

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