【摘要】：目的:探討AAV9介導(dǎo)的CTRP9過(guò)表達(dá)對(duì)糖尿病大鼠心肌纖維化的作用及其機(jī)制。方法:45只6周齡健康SD大鼠分為對(duì)照組、GFP組和CTRP9組,每組15只。GFP組和CTRP9組腹腔注射鏈脲佐菌素(STZ)造模,對(duì)照組腹腔注射生理鹽水;2周后,GFP組和CTRP9組分別經(jīng)尾靜脈緩慢注射攜帶GFP和CTRP9基因的AAV9,對(duì)照組同法給予生理鹽水。轉(zhuǎn)染12周后檢測(cè)血糖及血清CTRP9水平,進(jìn)行心肌Masson染色并計(jì)算膠原容積分?jǐn)?shù)(CVF)以評(píng)價(jià)大鼠心肌纖維化程度,應(yīng)用RT-PCR和Western blot分別檢測(cè)3組大鼠心肌TGF-β1/Smads通路中各因子mRNA和蛋白水平。結(jié)果:轉(zhuǎn)染12周后,與GFP組相比,CTRP9組大鼠血清CTRP9上升,血糖降低,CVF也降低(P0.05);同時(shí)TGF-β1、Smad2和Smad3 mRNA表達(dá)水平降低,Smad7 mRNA表達(dá)水平升高(P0.05),α-SMA、TGF-β1和p-Smad2/3蛋白表達(dá)水平降低,Smad7蛋白表達(dá)升高(P0.05)。結(jié)論:AAV9介導(dǎo)的CTRP9過(guò)表達(dá)可能通過(guò)調(diào)節(jié)TGF-β1/Smads信號(hào)通路來(lái)抑制糖尿病大鼠的心肌纖維化。
[Abstract]:Aim: to investigate the effect and mechanism of AAV9-mediated CTRP9 overexpression on myocardial fibrosis in diabetic rats. Methods Forty-five 6-week-old healthy SD rats were divided into control group (GFP group) and CTRP9 group (n = 15). Each group was treated with streptozotocin (STZ) by intraperitoneal injection of streptozotocin (STZ). After 2 weeks of intraperitoneal injection of normal saline into the control group, AAV9 carrying GFP and CTRP9 genes was slowly injected into the tail vein of the GFP group and the CTRP9 group, respectively, and the control group was given normal saline with the same method. After 12 weeks of transfection, the levels of blood glucose and serum CTRP9 were detected, myocardial Masson staining and collagen volume fraction (CVF) were used to evaluate the degree of myocardial fibrosis in rats. The levels of mRNA and protein in the TGF- 尾 1/Smads pathway of three groups were detected by RT-PCR and Western blot, respectively. Results: after 12 weeks of transfection, compared with GFP group, serum CTRP9 increased and blood glucose decreased in CTRP9 group (P0.05), while the expression of TGF- 尾 1, Smad2 and Smad3 mRNA decreased significantly (P0.05), and the expression of 偽 -SMA-TGF- 尾 1 and p-Smad2/3 protein decreased (P0.05). Conclusion the overexpression of CTRP9 mediated by AAV9 may inhibit myocardial fibrosis in diabetic rats by regulating the TGF- 尾 1/Smads signaling pathway.
【作者單位】： 鄭州大學(xué)第二附屬醫(yī)院心血管內(nèi)科;鄭州大學(xué)第二附屬醫(yī)院急診科;
【基金】：河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃項(xiàng)目201503094
【分類號(hào)】：R587.2

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