舒洛地特抑制单侧输尿管梗阻小鼠肾间质纤维化

目的 探讨舒洛地特对单侧输尿管梗阻(UUO)小鼠肾脏间质纤维化的作用,及其对肾小管上皮-间充质转化(EMT)和肾组织Jagged-1、Noteh1表达的影响.方法 雄性CD1小鼠60只随机分为:假手术组(A组),仅行腹膜切开后缝合;对照组(B组),行单侧输尿管结扎,术后予生理盐水0.1ml/d皮下注射;低剂量治疗组(C...

Sulodexide attenuates renal interstitial fibrosis in mice with ureteral obstruction

Objective To investigate the effect of sulodexide on renal interstitial fibrosis and the expression of Jagged-1,Notch1,vascular endothelial growth factor (VEGF)in unilateral ureteral obstruction (UUO) mice,and try to reveal the possible underlying mechanisms. Methods Sixty mice were divided into four groups randomly:group A (sham) was subjected to surgical manipulation but without ureteral ligation; group B(UUO+saline) was subjected to ureteral obstruction and received saline subcutaneously (s.c.) once daily; group C(UUO+LS) was subjected to ureteral obstruction and received sulodexide(6mg/kg) s.c. once daily; group D(UUO+HS) was subjected to ureteral obstruction and received sulodexide(12mg/kg) s.c. once daily. Mice were sacrificed at day 3,7 and 14 after operation respectively. The severity of renal interstitial fibrosis was determined by pathologic techniques. The content of -SMA,TGF-β1,VEGF,Jagged-1 and Notch1 were determined in the kidneys by immunohistochemical or biochemical techniques. Results The severity of interstitial fibrosis,expression of -SMA,TGF-β1 and Jagged-1 were increased,whereas expression of VEGF decreased significantly in obstructed kidney compared to sham-operated kidney. Treatment with sulodexide attenuated interstitial fibrosis,reduced expression of -SMA,TGF-β1 and Jagged-1 after UUO operation dramatically,without significant affect on the expression of VEGF. Expression of Notch1 was not detectable in CD1 mice kidneys by RT-PCR and Western Blot. Conclusions Sulodexide diminishes interstitial fibrosis in obstructed kidneys. Inhibition of EMT is most likely to be included,which may be related to downregulating the synthesis of TGF-β1 and Jagged-1. The mechanisms underlying these effects remain to be elucidated.