吡非尼酮对大鼠肾间质纤维化的防治作用研究

发布时间：2018-11-09 20:50

【摘要】：目的研究吡非尼酮(PFD)对大鼠肾间质纤维化的作用及其作用机制,为临床使用吡非尼酮提供理论依据。方法 24只标准雄性SD大鼠,随机分为3组:正常组(NC组)、模型组(M组)及吡非尼酮治疗组(S组)。M组及S组行左侧输尿管结扎术,复制肾间质纤维化模型。S组予吡非尼酮250 mg/(kg·d)灌胃,NC组及M组大鼠予等量1%羧甲基纤维素钠溶液灌胃。分别于手术后第1、3、5、7天处死各组大鼠各2只,取梗阻侧肾脏。HE染色观察各组肾组织病理变化,实时荧光定量聚合酶链反应(q RT-PCR)检测结缔组织生长因子(CTGF)m RNA表达水平,Western blot检测转化生长因子-β(TGF-β)及α-平滑肌激动蛋白(α-SMA)的蛋白表达水平。结果 NC组未显示肾纤维化,M组显示大鼠肾间质纤维化及炎症细胞浸润。NC组TGF-β、α-SMA蛋白表达均较低,M组TGF-β、α-SMA蛋白及CTGF m RNA表达较NC组均升高,差异有统计学意义(P0.05),且随着梗阻时间延长,各物质表达量增高,但第7天M组及S组上述物质表达量较第5天减少,且M组与S组之间表达差异无统计学意义(P0.05);S组上述物质各时间点表达则较M组均减少,差异有统计学意义(P0.05)。结论吡非尼酮可能通过抑制大鼠肾组织TGF-β和CTGF的表达进而减少成纤维细胞转化为肌成纤维细胞,减少细胞外基质(ECM)的沉积,发挥抗肾纤维化作用。
[Abstract]:Objective to study the effect and mechanism of pifenidone (PFD) on renal interstitial fibrosis in rats. Methods Twenty-four standard male SD rats were randomly divided into three groups: normal group (NC group), model group (M group) and pifenidone treated group (S group). M and S group) with left ureteral ligation. The rat model of renal interstitial fibrosis was induced by intragastric administration of pifenidone for 250 mg/ (kg d) in group S and 1% sodium carboxymethyl cellulose solution in group NC and group M. Two rats in each group were killed on the 1st day and 5th day after operation, and the obstructed kidneys were taken out. The pathological changes of renal tissue were observed by HE staining. Real-time fluorescent quantitative polymerase chain reaction (Q RT-PCR) was used to detect the expression of connective tissue growth factor (CTGF) m RNA). The expression of transforming growth factor-尾 (TGF- 尾) and 伪-smooth muscle activin (伪-SMA) were detected by Western blot. Results there was no renal fibrosis in NC group, but no renal fibrosis and inflammatory cell infiltration in M group. The expression of TGF- 尾 and 伪 SMA protein in NC group was lower than that in M group, and the expression of TGF- 尾, 伪 -SMA protein and CTGF m RNA in M group was higher than that in NC group. The difference was statistically significant (P0.05), and with the prolongation of the time of obstruction, the expression of each substance increased, but on the 7th day, the expression of these substances in group M and group S was lower than that in group 5. There was no significant difference in expression between group M and group S (P0.05). The expression of the above substances in group S was significantly lower than that in group M (P0.05). Conclusion pifenidone may inhibit the expression of TGF- 尾 and CTGF in rat renal tissue and thus reduce the fibroblast transformation into myofibroblasts, reduce the deposition of extracellular matrix (ECM), and play an antifibrotic role in renal fibrosis.
【作者单位】：南昌大学第一附属医院肾内科;北京大学深圳医院肾内科;南昌大学第一附属医院眼科;
【基金】：国家自然科学基金(No:81400372,81660129) 全国临床医药研究专项基金(No:L2012052) 广东省自然科学基金(No:S2013040015040) 江西省自然科学基金青年基金(No:20132BAB215004,20114BAB215036)
【分类号】：R692

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