吡非尼酮对大鼠肾间质纤维化的防治作用研究  

Effect of Pirfenidone on renal interstitial fibrosis in rats

作　　者：徐建华[1] 肖红波[2] 程玉花[1] 王瑜[1] 张桂玲[1] 吕金雷[1] 邵毅[3] 

机构地区：[1]南昌大学第一附属医院肾内科,江西南昌330006 [2]北京大学深圳医院肾内科,广东深圳518036 [3]南昌大学第一附属医院眼科,江西南昌330006

出　　处：《中国现代医学杂志》2017年第19期1-6,共6页China Journal of Modern Medicine

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)

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(P<0.05),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(P>0.05);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(P<0.05)。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。Objective To investigate the effect of Pirfenidone （PFD） on renal interstitial fibrosis in rat model of unilateral ureteral occlusion （UUO） and to reveal the anti -fibrosis mechanism of PFD. Methods Twenty -four standard male SD rats were randomly divided into three groups： normal control group（N）, UUO model group （M） and Pirfenidone treated group （S）. The rats of the M and S groups underwent left urethral ligation to make the renal interstitial fibrosis model. The S group was given PFD 250 mg/（kg·d） for gavage, meanwhile the N and M groups were given 1% sodium carboxymethyl cellulose solution for gavage. Two rats were sacrificed from each group on day 1, 3, 5 and 7 after UUO operation, the kidney of the obstructive side was taken for further research. In each group,pathological changes were observed by HE staining, qRT-PCR was applied to detect the mRNA expression of connective tissue growth factor （CTGF）, Western bolt was applied to detect the protein expressions of TGF-βand α-SMA. Results There was obvious renal interstitial fibrosis in the M group. Compared with the N group, the expressions of TGF-βand α-SMA proteins and the mRNA expression of CTGF were significantly increased in the M group（P〈 0.05）. Compared with the M group, the expressions of above parameters in the S group were decreased significantly（P〈 0.05）. The level of TGF -βwas positively correlated with the level of α-SMA （P〈 0.05）. Conclusions Pirfenidone has anti -fibrosis effect on rat UUO model by inhibiting renal TGF -β and CTGF expressions, which may control the fibroblast transformation and reduce the extracellular matrix deposition in the renal tissue.

关 键 词：吡非尼酮 单侧输尿管梗阻 肾间质纤维化 结缔组织生长因子 转化生长因子-Β α- 平滑肌肌动蛋白 

分 类 号：R-332[医药卫生]