EMD-PLGA NPs延缓5/6肾切除大鼠诱发慢性肾功能衰竭

Emodin-polylactic-co-glycolic acid NPs delays chronic renal failure by 5/6 nephrectomy

目的探讨大黄素-聚乳酸/羟基乙酸共聚物纳米粒(EMD-PLGA NPs)对5/6肾切除大鼠残余肾组织的保护作用及可能的机制。方法大鼠随机分为假手术组8只(sham组),造模成功24只后随机分为模型组8只(model组)、大黄素组8只(EMD组)、纳米粒组8只(NPs组),期间检测大鼠24 h尿蛋白定量、血尿素氮(BUN)和血肌酐(SCr),光镜下观察肾组织病理变化,分别用RT-PCR法和免疫组织化学法检测肾组织转化生长因子-β1(TGF-β1)及结缔组织生长因子(CTGF)mRNA及蛋白表达。结果药物干预后,与sham组比较,model组24 h尿蛋白定量、BUN、SCr及TGF-β1和CTGF mRNA及蛋白水平上升(P<0.01);与model组比较,EMD组、NPs组24 h尿蛋白定量、BUN、SCr、TGF-β1、CTGF mRNA及蛋白水平下降(P<0.01);与EMD组比较,NPs组24 h尿蛋白定量、BUN、SCr、TGF-β1和CTGF mRNA及蛋白水平下降(P<0.01)。结论与普通EMD比较,EMD-PLGA NPs能更好地延缓肾病慢性进展。

Objective To explore the kidney protecting effect and possible mechanism under which the renal tissues in 5/6 nephreetomy rats was intervened by emodin-polylactic-co-glycolic acid nanoparticles. Methods Rats were randomly divided into two groups, eight as sham-operated group and twenty-four as model group. Twenty-four rats in model group were randomly and equally assigned into model group （model group）, emodin group eight（EMD） and nanopartieles group eihgt （NPs）. Drugs were given to rats in different groups for a total 8 weeks, then 24 h urine protein, blood urea nitrogen （BUN）and creatinine （SCr） were measured; kidney pathological changes were observed under optical microscope; protein and mRNA expression of growth factor beta-1 （TGF-β1） as well as con nective tissue growth factor （CTGF） in renal tissues were detected respectively by RT-PCR methods and immuno histochemistry. Results After treated with drugs, compared with sham group,24 h urine protein, blood urea nitro- gen, serum creatinine, mRNA and protein expression of TGF-β1 and CTGF of rats in model group were both increased（P 〈0. 01 ）. Compared with model group,24 h urine protein,blood urea nitrogen,serum creatinine, mRNA and protein expression of TGF-β1 and CTGF of rats in EMD group and NPs group were both decreased（P 〈0. 01 ） ; Compared with EMD group ,24 h urine protein ,blood urea nitrogen ,serum creatinine, mRNA and protein expression of TGF-IM and CTGF of rats in NPs group were both decreased（P 〈0. 01 ）. Conclusions EMD-PLGA NPs inhibits renal fibrosis and slows down the progress of chronic kidney disease.