丹参粉针剂对单侧输尿管结扎大鼠肾纤维化的保护作用  

Protective effect of Salvia miltiorrhiza powder for injection on renal fibrosis induced by unilateral ureteral obstruction in rats

作　　者：姜汉杰[1] 李婉[1] 王辰[1] 郭涌斐 赵欣[1] 孙懿[1] 蒲小平[1,2] 

机构地区：[1]北京大学药学院分子与细胞药理学系,北京100191 [2]北京大学天然药物与仿生药物国家重点实验室,北京100191

出　　处：《中国新药杂志》2015年第22期2606-2611,2631,共7页Chinese Journal of New Drugs

摘　　要：目的:研究丹参粉针剂对单侧输尿管结扎(unilateral ureteral obstruction,UUO)肾纤维化模型大鼠的保护作用。方法:SD大鼠随机分为假手术组、模型组、阳性对照组(福辛普利混悬液10 mg·kg-1·d-1)和丹参粉针剂低、中、高剂量组(20,40和80 mg·kg-1·d-1)。除假手术组外,其余各组UUO造模,造模后给予相应药物治疗14 d后,眼眶静脉丛取血,分离血清,测定尿素氮(BUN)、血肌酐(s Cr)、Ⅳ型胶原(CIV)含量,并进行肾组织病理HE,Masson染色,及肾组织TGF-β,α-SMA免疫组化染色。结果:丹参中、高剂量组大鼠肾功能指标BUN较模型组显著降低(P<0.05),丹参各剂量组s Cr较模型组显著降低(P<0.01或P<0.05);丹参高剂量组纤维化指标CIV较模型组显著降低(P<0.01);肾组织病理HE染色显示丹参各剂量组均能改善肾损伤情况;Masson染色显示胶原纤维显著减少(P<0.01);免疫组织化学显示,肾组织中TGF-β及α-SMA表达均显著性下降(P<0.01)。结论:丹参粉针剂对单侧输尿管结扎模型所致的大鼠肾纤维化具有保护作用,作用机制主要为直接抑制纤维化通路TGF-β1的激活。Objective： To investigate the protective effect of Salvia mihiorrhiza powder for injection on re- nal fibrosis induced by unilateral ureteral obstruction （UUO） in rats. Methods： SD rats were randomly divided in- to groups, and renal fibrosis was induced by UUO surgery except the sham operation control. After the surgery, rats were treated with intraperitoneal injection of Salvia miltiorrhiza powder for injection （20, 40 and 80 mg·kg^-1·d^-1） or oral fosinopril （ 10 mg·kg^-1·d^-1 , positive control） for 14 days. At the end of the experiment, blood was taken from each rats under orbit, and serum was separated. The blood urea nitrogen （BUN） , serum creatinine （sCr） and type IV collagen （CIV） were measured. Renal pathology was assessed by hematoxylin-eosin （HE） and Masson trichrome staining. The expression of transforming growth factor-β1 （TGF-β1） and α-smooth muscle actin （α- SMA） were measured by the immunohistochemical staining. Results： Treatment with Salvia mihiorrhiza powder for injection improved the function of kidney by reducing the BUN and sCr levels. Salvia mihiorrhiza powder for injec- tion ameliorated the injuries of kidney, reduced the level of fibrosis and CIV expression in renal sections. Immuno- histochemistry showed that Salvia miltiorrhiza powder for injection down-regulated the expression of TGF-β1 and α- SMA. Conclusion： Salvia miltiorrhiza powder for injection has protective effect on UUO-induced renal fibrosis in rats. The mechanism may related to directly inhibit the TGF-β1 pathway and resultant fibrosis.

关 键 词：丹参粉针剂 单侧输尿管结扎 肾纤维化 

分 类 号：R961[医药卫生—药理学]