淫羊藿苷抗压力超负荷致心肌纤维化的研究

发布时间：2018-04-08 18:28

本文选题：Ica　切入点：TNF-α　出处：《遵义医学院》2014年硕士论文

【摘要】：目的：研究淫羊藿苷(Icariin，Ica)对腹主动脉缩窄后心肌纤维化的影响并探讨其可能的作用机制。方法：建立腹主动脉缩窄后心肌纤维化模型；实验动物分为假手术组（S组）、模型组（MF组）、Ica低（40mg/kg/d，L-Ica）、高（80mg/kg/d，H-Ica）剂量组，制模后每天观察大鼠一般情况，并于次日开始给药，S组与MF组给予等体积双蒸水灌胃，连续给药50d后经腹腔麻醉测左室心功能指数，后取左室前壁心肌组织行H.E.和MASSON染色观察病理学改变，，并计算单位视野下纤维化面积以评价心肌纤维化程度；Real-timeRT-PCR法检测心肌组织中TGF-β1、Smad2、MMP-9、TIMP-1、PPARα、PPARγ、TNF-α、NF-κB、IκBα mRNA的表达；免疫组化法半定量测定心肌组织中MMP-9、pNF-κB65的表达；Western Blot法定量TGF-β1、p-Smad2、MMP-9、TIMP-1、PPARα、TNF-α、pNF-κB65、IκBα蛋白的表达。结果：与S组比较，MF组大鼠毛色晦暗，行动迟缓，蜷缩，鼻腔眼眶有溢血，进食量明显减少，体重下降；心肌肥大、变性、坏死，排列紊乱，炎性细胞浸润，胶原增多，血管壁中层增厚，大量基质沉积，冠脉血管壁外膜纤维化，单位视野下纤维化面积增多（P 0.01）；大鼠心肌组织中TGF-β1、Smad2、MMP-9、TIMP-1、PPARγ、TNF-α、pNF-κB65、IκBα mRNA和蛋白的表达均上调，PPARα mRNA和蛋白的表达下调（P 0.01或P 0.05）。与MF组比较，L-Ica和H-Ica组上述情况均有所减轻，心肌纤维化程度显著减轻，单位视野下纤维化面积明显减小（P 0.01)；大鼠心肌组织中TGF-β1、Smad2、MMP-9、TIMP-1、PPARγ、TNF-α、pNF-κB65、IκBα mRNA和蛋白的表达均下调，PPARα mRNA和蛋白的表达上调（P 0.01或P 0.05）。结论：Ica具有明显抑制腹主动脉缩窄所致心肌纤维化的作用，其作用机制可能与抑制TGF-β1/Smad2，MMP-9和TIMP-1、TNF-α、pNF-κB65、IκBα的表达，升高PPARα表达有关。
[Abstract]:Aim: to study the effect of Icariin Icaa on myocardial fibrosis after abdominal aorta constriction and its possible mechanism.After 50 days of continuous administration, the left ventricular cardiac function index was measured by intraperitoneal anesthesia, and the left ventricular anterior wall myocardial tissue was taken for H.E.Pathological changes were observed with MASSON staining, and the area of fibrosis in unit field was calculated to evaluate the degree of myocardial fibrosis. Real-time RT-PCR was used to detect the expression of TGF- 尾 1, Smad2, MMP-9, TIMP-1PPAR 伪, TNF- 魏 B, I 魏 B 伪 in myocardial tissue.The expression of MMP-9 pNF- 魏 B65 in myocardial tissue was determined by immunohistochemical method. The expression of TGF- 尾 _ 1 pNF- 魏 B _ (65) I 魏 B 伪 was determined by Western Blot assay.Results: compared with group S, the rats of MF group had dark color, slow movement, curling up, bleeding in the nasal cavity and orbit, decreased food intake, decreased body weight, hypertrophy, degeneration, necrosis, disorder, infiltration of inflammatory cells, and increase of collagen.Compared with the MF group, the above conditions in the L-Ica and H-Ica groups were alleviated, and the degree of myocardial fibrosis was significantly alleviated.The area of fibrosis decreased significantly in the unit field of vision, and the expression of TGF- 尾 1, Smad2, MMP-9, TIMP-1, TNF- 伪, pNF- 魏 B65, I 魏 B 伪, mRNA and protein in rat myocardial tissue down-regulated the expression of PPAR 伪 mRNA and protein (P0.01 or P0.05A).Conclusion 1: Ica can inhibit the myocardial fibrosis induced by abdominal aortic coarctation. The mechanism may be related to the inhibition of the expression of TGF- 尾 1 / Smad2MMP 9 and TIMP-1 TNF- 伪, pNF- 魏 B 65, I 魏 B 伪, and the increase of PPAR 伪 expression.
【学位授予单位】：遵义医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

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