前列腺素E1对局灶节段性肾小球硬化模型大鼠肾血管内皮生长因子表达的影响

Effects of Lipo-PGE1 and Dexamethasone on Rats with Experimental Focal Segmental Glomerulosclerosis

目的:探讨前列腺素E1脂微球载体制剂(L ipo-PGE1),地塞米松对局灶节段性肾小球硬化模型大鼠的影响。方法:用单侧肾切除加1周后静脉注射多柔比星(5 mg/kg)的方法建立局灶节段性肾小球硬化(FSGS)大鼠模型,设立假手术组为正常对照组,同时设立FSGS模型组、地塞米松治疗组、L ipo-PGE1治疗组、L ipo-PGE1联合地塞米松治疗组。检测各组术后第2,6,10周末的尿蛋白及第10周末血清尿素氮、肌酐、总蛋白、白蛋白及肾组织病理改变,并应用免疫组化方法检测肾组织内胶原Ⅰ(ColⅠ)、胶原Ⅲ(ColⅢ)的沉积和血管内皮生长因子(VEGF)蛋白质的表达。结果:L ipo-PGE1治疗组比FSGS模型组尿蛋白排泄量明显减少,血肌酐、尿素氮水平下降,肾小球增生、硬化程度及肾小管间质病变程度明显减轻(P<0.01);免疫组化显示,模型组肾组织胶原Ⅰ、胶原Ⅲ沉积增多,VEGF蛋白表达减少,L ipo-PGE1治疗组比模型组减少(P<0.01),地塞米松治疗组比模型组尿蛋白排泄量增加,血肌酐、尿素氮水平上升,肾小球增生、硬化程度及肾小管间质病变程度加重,L ipo-PGE1联合地塞米松治疗组表现与地塞米松治疗组无显著差异(P>0.05)。结论:L ipo-PGE1对局灶节段性肾小球硬化模型大鼠肾脏损害有一定的保护作用,可能与影响肾小球足细胞VEGF表达有关,但是不能纠正由于地塞米松导致的FSGS模型加重的表现。

Objective： To study the effects of Lipo-PGE1 and dexamethasone on experimental focal segmental glomerulosclerosis in rats. Methods： Rats were randomly assigned into following groups： experimental focal segmental glomerulosclerosis model group, Lipo-PGE1 treatment group, dexamethasone treatment group, Lipo-PGE1 and dexamethasone combination treatment group, normal control group. Rats in normal control group were subjected to Sham operation and injected with normal saline after one week through the tail vein. Rats in other groups were uni-nephrectomized and injected with adriamycin （5 mg/kg） after one week through the tail vein. The dose of Lipo-PGE1 was 10μg·kg^-1·d^-1 The dose of dexamethasone was 10 mg·kg^-1·d^-1. Urinary protein excretion, serum total protein and albumin, serum creatinine（Scr）, blood urea nitrogen （BUN） were measured 2,6 and 10 weeks after operation. Renal pathology was evaluated at the 10th week. Immunohistochemistry was used to examine the expression of collagen Ⅰ, collagen Ⅲ, VEGF in the glomerular tissue. Results：Lipo-PGE1 not only reduced urinary protein,Scr and BUN, but also significantly reduced glomerular mesa-ngial proliferation and glomerularselerosis. Immunohistoehemistry staining indicated that increased collagen Ⅰ, collagen Ⅲ, VEGF expression in model control group compared to treatment groups （P〈0.01）. At the same time, increased collagen Ⅰ, collagen Ⅲ and VEGF expression in dexamethasone treatment groups compared to model control group （P〈0.01）. There was no prominent difference between dexamethasone treatment groups and combination treatment group. Conclusion： Lipo- PGE1 had a renoprotective effect on experimental glomerulosclerosis in rats, but Lipo-PGE1 can not reverse the injure causing by dexamethasone. Lipo - PGE1 may inhibit the progression of focal segmental glomerulosclerosis by reducing the deposition of extra cellular matrix, which may be related to the up regulating expression of VEGF in glomeruli. It may be an effective agent for the treatment of focal segmental glomerulosclerosis.