低分子量肝素对大鼠肾纤维化的预防作用

Preventive Effect of Low-Molecular-Weight Heparin on Renal Fibrosis of Mice

目的:观察低分子量肝素(LMWH)对大鼠肾纤维化的预防作用及机制。方法:健康SD大鼠54只随机分为假手术组、模型组、LMWH组,后两组采用单侧输尿管结扎术(UUO)制作肾间质纤维化大鼠模型,LMWH组术后予LMWH皮下注射,每组分别于手术后第5天、第10天、第15天处死6只大鼠,取肾组织HE染色切片通过光镜观察各组大鼠肾组织形态,Masson染色后进行计算肾间质损伤指数,免疫组织化学方法检测TGF-β1、MMP-2表达。结果:同期模型组肾间质损伤指数、TGF-β1表达高于假手术组(P<0.05),MMP-2表达低于假手术组(P<0.05);术后10 d和15 d LMWH组肾间质损伤指数及TGF-β1表达低于模型组(P<0.05),MMP-2表达高于模型组(P<0.05)。结论:LMWH可能是通过抑制TGF-β1表达、促进MMP-2表达,从而减轻UUO大鼠肾小管间质纤维化。

Objective： To investigate the preventive effect and mechanism of low-molecular-weight heparin on renal fibrosis of mice. Methods： Fifty- four SD mice were randomly divided into 3 groups ： Sham-operation group, unilateral ureteral obstruction group （UUO） , and LMWH group. The latter two groups adopted UUO to build models, and LMWH group were injected with LMWH after surgery. 6 mice of each group were executed randomly on the days 5, 10, 15 after surgery. Immunohistochemistry was performed on obstructed renal tissue to detect TGF-~I and MMP-2 expression. Histological studies were also performed by HE and Masson staining. Results： The tubulointerstitial damage indexes, the expression of TGF-131 were significantly higher than that of sham-operation group （ P 〈 0.05 ）, the ex- pression of MMP-2 was significantly lower than that of sham-operation group （P 〈 0.05 ） ; On l0 d and 15 d after surgery, the tubulointerstitial damage indexes and the expression of TGF-~I in LMWH group were significantly lower than that of UUO group （ P 〈 0.05 ）, the expression of MMP-2 was significant- ly higher than that of UUO group （ P 〈 0.05 ）. Conclusion： LMWH may attenuate development of tu- bulointerstitial fibrosis by down-regulation the expression of TGF-I31 and up-regulation of the expression of MMP-2 in UUO mice.