本文選題：球形脂聯(lián)素　切入點(diǎn)：2型糖尿病　出處：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:建立2型糖尿病(T2DM)大鼠模型,觀察不同時(shí)間段(4、8、12周)胸主動(dòng)脈組織中轉(zhuǎn)化生子因子β1(TGF-β1)、Smad3、Smad7、1型膠原蛋白(Col-1)的表達(dá)情況;同時(shí)比較球形脂聯(lián)素(gAd)干預(yù)后4、8、12周大鼠胸主動(dòng)脈組織中TGF-β1、Smad3、Smad7、Col-1與T2DM大鼠模型組的變化,探討gAd與TGF-β1/Smads信號(hào)通路之間的關(guān)系及其對(duì)T2DM大鼠動(dòng)脈粥樣硬化(AS)保護(hù)作用的機(jī)制,為臨床拓展防治T2DM大血管并發(fā)癥提供新思路。方法:90只雄性sprague-dawley(SD)大鼠隨機(jī)分為正常對(duì)照組(N組,n=24)和T2DM造模組(n=66),成模的53只再分為T2DM組(D組,n=26)、干預(yù)組(A組,n=27)。A組給予gAd 10μg·kg~(-1)·d~_(-1)腹腔推注,余兩組給予等量生理鹽水。各組分別于4、8、12周末隨機(jī)取8只大鼠麻醉后采血,測(cè)空腹血糖(FPG)、總膽固醇(TC)、甘油三酯(TG)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C);留取胸主動(dòng)脈標(biāo)本,行HE染色后光鏡觀察其形態(tài)學(xué)改變,并用免疫組化法測(cè)Col-1的表達(dá),應(yīng)用蛋白免疫印跡(Western blotting)、實(shí)時(shí)熒光定量聚合酶鏈反應(yīng)(RT-PCR)法測(cè)TGF-β1、Smad3、Smad7蛋白及其mRNA的表達(dá)。據(jù)實(shí)驗(yàn)結(jié)果及統(tǒng)計(jì)學(xué)處理分析,探討它們之間的關(guān)系。結(jié)果:1.各時(shí)間段中,D組大鼠FPG、TC、TG、LDL-C明顯高于N組,而HDL-C降低;A組FPG、TC、TG、LDL-C均低于相應(yīng)D組,而HDL-C較之升高(P均0.05)。2.HE染色顯示:N組大鼠動(dòng)脈壁內(nèi)、中、外膜三層結(jié)構(gòu)完整,管壁光滑,內(nèi)膜及中層細(xì)胞排列規(guī)則。D組可見動(dòng)脈壁內(nèi)、中、外膜界限不清、輕度紊亂,內(nèi)膜完整性破壞,內(nèi)皮細(xì)胞部分脫落,中膜平滑肌細(xì)胞形態(tài)多樣,數(shù)量增多,排列不規(guī)則;并且隨著T2DM病程延長(zhǎng),上述病變呈時(shí)間依賴性加重。g Ad干預(yù)后,A組上述病變較相應(yīng)D組分別減輕,且隨著干預(yù)時(shí)間延長(zhǎng),胸主動(dòng)脈AS程度呈時(shí)間依賴性減輕。3.免疫組化、Western blotting和RT-PCR法顯示:D組TGF-β1、Smad3、Col-1的表達(dá)明顯多于N組,而Smad7表達(dá)減少(P均0.05);A組TGF-β1、Smad3、Col-1表達(dá)明顯低于同期D組,而Smad7表達(dá)增多。且隨著gAd干預(yù)時(shí)間延長(zhǎng),TGF-β1、Smad3、Col-1的表達(dá)逐漸減少,Smad7表達(dá)逐漸增多(P0.05)。結(jié)論:1.T2DM模型組大鼠胸主動(dòng)脈TGF-β1、Smad3、Col-1表達(dá)水平明顯升高,而Smad7表達(dá)下降,并且隨著病程的延長(zhǎng),TGF-β1、Smad3、Col-1水平依次升高,Smad7依次降低,與光鏡下胸主動(dòng)脈AS程度一致,提示TGF-β1/Smads信號(hào)通路的異常表達(dá)可能參與了T2DM大鼠AS的發(fā)生、發(fā)展。2.gAd干預(yù)組大鼠胸主動(dòng)脈TGF-β1、Smad3、Col-1表達(dá)水平明顯下降,而Smad7表達(dá)升高,并且隨著干預(yù)時(shí)間延長(zhǎng),TGF-β1、Smad3、Col-1水平依次下降,Smad7依次升高。光鏡下示胸主動(dòng)脈AS程度逐漸減輕,提示gAd通過(guò)上調(diào)Smad7或下調(diào)TGF-β1、Smad3來(lái)干擾TGF-β1/Smads傳導(dǎo)通路,進(jìn)一步抑制Col-1等致纖維化因子的生成及沉積,發(fā)揮抗血管壁纖維化作用,從而緩解T2DM大鼠AS進(jìn)程。
[Abstract]:Objective: to establish a rat model of type 2 diabetes mellitus (T2DM) and to observe the expression of transforming progenitor factor 尾 1 (TGF- 尾 1) in thoracic aorta at 12 weeks. At the same time, the changes of TGF- 尾 1, Smad3, Smad7 and Col-1 in thoracic aorta of rats treated with globular adiponectin (Aden) for 12 weeks were compared with those of T2DM rats, and the relationship between TGF- 尾 1/Smads signaling pathway and gAd and the protective mechanism of TGF- 尾 1/Smads on atherosclerosis in T2DM rats were investigated. Methods 90 male Sprague-dawley SD rats were randomly divided into normal control group (n = 24) and T2DM model group (n = 53). 53 rats were divided into T2DM group D group (n = 26) and intervention group A group (n = 10 渭 g 路kg ~ (-1)) d ~ (-1) 路d ~ (-1). The other two groups were given the same amount of normal saline. At the end of 12 weeks, 8 rats in each group were randomly selected for blood collection after anaesthesia. Fasting blood glucose (FPG), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were measured, and the morphological changes of thoracic aorta were observed by light microscope after HE staining, and the expression of Col-1 was detected by immunohistochemical method. The expression of TGF- 尾 1 Smad3 Smad7 protein and its mRNA were detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Results 1. The LDL-C of group D was significantly higher than that of group N, while the LDL-C of group A was lower than that of group D, while the level of HDL-C in group A was lower than that of group D, and HDL-C was significantly higher than that of group N by 0.05).2.HE staining. The three layers of the adventitia were complete, the wall of the tube was smooth, and the inner wall of artery was found in group D with regular arrangement of intimal and medial cells. The boundary of the middle and outer membrane was not clear, there was slight disorder, the integrity of the intima was destroyed, the endothelial cells were partially shed, and the morphology of smooth muscle cells of the media was various. With the prolongation of the course of T2DM, the above pathological changes were aggravated in a time dependent manner. After the intervention of Ad, the above lesions in group A were alleviated respectively than those in group D, and with the prolongation of the duration of intervention. The expression of TGF- 尾 1, Smad3 and Col-1 in group D was significantly higher than that in group N, while the expression of Smad7 in group A was significantly lower than that in group D, and the expression of TGF- 尾 1 and Smad3 Col-1 in group A was significantly lower than that in group D at the same time. However, the expression of Smad7 was increased, and the expression of TGF- 尾 1, Smad3, Col-1 was gradually decreased with the prolongation of gAd intervention. Conclusion the expression of TGF- 尾 1, Smad3 and Col-1 in thoracic aorta of T2DM group was significantly increased, while the expression of Smad7 was decreased in the TGF- 尾 1 Smad3 Col-1 of thoracic aorta of rats treated with T2DM. With the prolongation of the course of disease, the level of TGF- 尾 1, Smad3 and Col-1 increased and decreased in turn, which was consistent with the degree of thoracic aortic atherosclerosis under light microscope, suggesting that the abnormal expression of TGF- 尾 1/Smads signal pathway may be involved in the pathogenesis of as in T2DM rats. 2. The expression of TGF- 尾 1 and Smad3 Col-1 in thoracic aorta of rats treated with Ad significantly decreased, while the expression of Smad7 increased, and the level of Smad3 Col-1 decreased in turn with the prolongation of intervention time. The degree of as in thoracic aorta decreased gradually under light microscope. It is suggested that gAd may interfere with the TGF- 尾 1/Smads pathway by up-regulating Smad7 or down-regulating TGF- 尾 _ 1 / Smad3, further inhibit the formation and deposition of fibrogenic factors such as Col-1, and play an anti-vascular fibrosis role, thereby alleviating the process of as in T2DM rats.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2

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