本文選題：周期性張應(yīng)變　切入點(diǎn)：血管平滑肌細(xì)胞　出處：《上海交通大學(xué)》2012年碩士論文　論文類型：學(xué)位論文

【摘要】：血管重建(remodeling)是高血壓、動脈粥樣硬化等心血管疾病共同的發(fā)病基礎(chǔ)和基本的病理過程。力學(xué)因素在血管重建中起著重要作用。高血壓血管重建的主要特征之一是血管承受的周向張應(yīng)變(應(yīng)力)升高,細(xì)胞外基質(zhì)(extracellular matrix,ECM)成分表達(dá)異常,導(dǎo)致血管纖維化�？梢�,周期性血管的周向張應(yīng)變與高血壓血管重建的發(fā)生和發(fā)展密切相關(guān)。因此,研究張應(yīng)變影響血管壁細(xì)胞外基質(zhì)表達(dá)的調(diào)控機(jī)制,對于尋找高血壓血管重建的防治措施具有重要的理論和臨床意義。 本研究復(fù)制了腹主動脈縮窄制作大鼠高血壓動物模型,以正常血壓(假手術(shù)組)大鼠為對照,探討高血壓狀態(tài)下,胸主動脈細(xì)胞外基質(zhì)的變化。同時,模擬高血壓在體動脈承受的張應(yīng)變狀態(tài),用Flexercell細(xì)胞張應(yīng)變加載系統(tǒng)對大鼠血管平滑肌細(xì)胞(vascular smooth muscle cells, VSMCs)施加周期性張應(yīng)變,加載條件為:頻率統(tǒng)一為1.25 Hz,幅度分別為0(正常靜態(tài))、5%(正常血壓狀態(tài))和15%(高血壓狀態(tài)),加載時間均為12 h。然后,大鼠各組主動脈組織和各組VSMCs,用Western blotting、Real time RT-PCR技術(shù)檢測ECM,包括I型膠原、III型膠原、彈性蛋白和miR-21的表達(dá)。用miR-21抑制因子(inhibitor)抑制VSMCs的miR-21表達(dá),以探討miR-21是否參與周期性張應(yīng)變誘導(dǎo)大鼠VSMCs細(xì)胞外基質(zhì)的調(diào)控。 結(jié)果顯示:①與假手術(shù)組相比,術(shù)后2W組動物胸主動脈的ECM和miR-21的表達(dá)顯著上升;術(shù)后4W動物胸主動脈的I型膠原、III型膠原和miR-21表達(dá)顯著上升,彈性蛋白表達(dá)下降非常顯著;②與靜態(tài)組和5%張應(yīng)變組相比,15%張應(yīng)變組VSMCs的I型膠原表達(dá)無顯著性差異,III型膠原表達(dá)顯著升高,彈性蛋白和Smad7表達(dá)顯著下降。張應(yīng)變加載組VSMCs的miR-21表達(dá)均明顯上調(diào);③抑制miR-21表達(dá),降低了周期性張應(yīng)變條件下VSMCs的III型膠原蛋白水平表達(dá),上調(diào)了miR-21預(yù)測靶蛋白Smad7的表達(dá)。 上述結(jié)果表明,高血壓狀態(tài)下,胸主動脈ECM表達(dá)異常,導(dǎo)致動脈順應(yīng)性明顯下降。病理性周期性張應(yīng)變也誘導(dǎo)了VSMCs的ECM異常表達(dá)。在病理性周期性張應(yīng)變作用下,miR-21表達(dá)上調(diào),其下游靶蛋白Smad7表達(dá)下調(diào),血管膠原蛋白表達(dá)增加,提示Smad7可能通過參與血管膠原蛋白表達(dá)調(diào)控,進(jìn)而參與了對血管纖維化的負(fù)調(diào)控;Smad7有可能成為治療血管纖維化的一個新靶標(biāo)。
[Abstract]:Vascular remodeling is hypertension, The common pathogenesis and basic pathological process of cardiovascular diseases such as atherosclerosis. Mechanical factors play an important role in vascular remodeling. One of the main characteristics of vascular remodeling in hypertension is the increased circumferential tensile strain (stress) of blood vessels. The abnormal expression of extracellular matrix ECM leads to vascular fibrosis. It can be seen that the circumferential strain of periodic blood vessels is closely related to the occurrence and development of vascular remodeling in hypertension. It is of great theoretical and clinical significance to study the regulation mechanism of tension strain on the expression of extracellular matrix in vascular wall. In this study, a rat model of hypertension was established by coarctation of abdominal aorta. The changes of extracellular matrix of thoracic aorta were studied in rats with normal blood pressure (sham operation group) as control. The tension strain of vascular smooth muscle cells (VSMC s) in vascular smooth muscle cells (VSMC) of rats was subjected to cyclic strain by Flexercell cell strain loading system. The loading conditions are as follows: the frequency is 1. 25 Hz, the amplitude is 0 (normal static state of blood pressure) and the loading time is 12 hours. The expression of Western blotting real time RT-PCR, including type I collagen III, elastin and miR-21, was detected by Western blotting real time RT-PCR in aorta and VSMC of rats. The miR-21 expression of VSMCs was inhibited by miR-21 inhibitor. To investigate whether miR-21 is involved in the regulation of extracellular matrix of rat VSMCs induced by cyclic tensile strain. The results showed that the expression of ECM and miR-21 in thoracic aorta increased significantly in 2 W group compared with that in sham operation group, and the expression of type I collagen III and miR-21 in thoracic aorta of 4 W group increased significantly 4 W after operation. There was no significant difference in the expression of type I collagen in VSMCs of 15% strain group compared with static group and 5% strain group. The expression of VSMCs miR-21 in tension-strain loading group was significantly decreased, and the expression of III type collagen in VSMCs was decreased under cyclic tension strain, and the expression of miR-21 predictive target protein Smad7 was up-regulated in the group of tension-strain loading, which inhibited the expression of miR-21, decreased the expression of III type collagen protein in VSMCs under cyclic tension strain, and up-regulated the expression of miR-21 predictive target protein Smad7. These results indicate that abnormal expression of ECM in thoracic aorta leads to a decrease in arterial compliance under hypertension. Pathological cyclic tension strain also induces abnormal expression of ECM in VSMCs. The expression of miR-21 is upregulated under the action of pathological cyclic tension strain. The downstream target protein Smad7 expression was down-regulated and the vascular collagen protein expression increased, suggesting that Smad7 may be involved in the regulation of vascular collagen protein expression. Therefore, Smad7 may be a new target for the treatment of vascular fibrosis.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R363

【共引文獻(xiàn)】

相關(guān)會議論文 前2條

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相關(guān)博士學(xué)位論文 前2條

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2 張軍;人體鼻腔結(jié)構(gòu)與功能自適應(yīng)生物力學(xué)模型的基礎(chǔ)性研究[D];大連理工大學(xué);2007年

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本文編號：1616431