槲皮素对大鼠慢性环孢素肾病的保护作用

Protective effects of quercetin on chronic cyclosporine nephropathy in rats

目的建立慢性环孢素A肾病大鼠模型,观察槲皮素对环孢素A导致慢性肾损害的影响。方法在低盐饮食基础上将SD大鼠分为四组:环孢素模型组、槲皮素干预组素、正常对照组、溶剂对照组。慢性环孢素肾病采用橄榄油稀释环孢素A灌药造模,槲皮素灌药干预。4周后处死,分别测定肾功能、尿蛋白和体重变化;HE、Mas-son染色评判肾脏组织病理学改变及纤维化程度;免疫组化检测肾脏组织TGF-β1的表达情况。结果①环孢素模型和槲皮素干预组大鼠体重明显下降,其血肌酐水平和尿蛋白排泄量均较两对照组明显升高(P<0.01),但槲皮素干预组上述指标改变明显低于环孢素模型组(P<0.05)。②环孢素模型组肾脏病理组织学改变主要为小管间质损伤,间质纤维化,小管萎缩;槲皮素干预后肾小管损伤以及间质纤维化积分明显低于环孢素模型组(P<0.01)。③环孢素模型和槲皮素干预组肾组织TGF-β1较两对照组明显上调(P<0.01),但槲皮素干预组肾组织TGF-β1表达明显低于环孢素模型组(P<0.05)。结论槲皮素对慢性环孢素肾病有一定的保护作用,可能与降低尿蛋白排泄、下调肾组织TGF-β1的表达,延缓肾小管间质纤维化进程有关。

Objective To observe the effect of quercetin on cyclosporine A （CsA） -induced chronic renal tubulointerstitial injury through establishing rat chronic cyclosporine nephropathy. Methods Male SD rats were given low - sodium diet for 1 week and then randomly divided into normal control, CsA model group （intragastric administration with CsA was dissolved in olive oil）, quercetin treatment and solvent control groups （intragastric administration with olive oil） . CsA was dissolved in olive oil and intragastrically applied to induce chronic renal injury. Four weeks after quercetin treatment, rats were sacrificed and the body weight, serum creatinine and urinary protein were measured, respectively. Hematoxylin - eosin （HE） and Masson staining were performed to evaluate the morphological changes and renal tissue score. The transforming growth - β1 （ TGF - β1 ） expression in renal tissue was detected by immunochemical assay. Results Quercetin treatment alleviated CsA - induced decrease of body weight and increase of serum creatinine and urinary protein. Compared with CsA group, tubulointerstitial injury with interstitial fibrosis and tubular atrophy was attenuated in quercetin treatment guoup. In addition, quercetin reduced CsA - induced TGF -β1 protein expression. Conclusion Quercetin could attenuate CsA -induced chronic renal injury and this effect might be in part related to decreasing urinary protein excretion, downregulating TGF- β1 expression and halting the progression of tubulointerstitial fibrosis.