阿托伐他汀对单侧输尿管梗阻大鼠肾小管间质中核因子-κB表达的影响

Effects of Atorvastatin on Expression of NF-κB in Unilateral Ureteral Obstruction Rats

目的观察单侧输尿管梗阻(UUO)大鼠肾小管间质核转录因子-κB(NF-κB)的动态表达及阿托伐他汀对其的影响。方法将45只大鼠随机分为假手术组、模型组及阿托伐他汀治疗组(简称阿乐组),后两组行左侧输尿管结扎术。阿乐组术前3d开始阿托伐他汀(10mg.kg-1.d-1)灌胃,余两组予等量生理盐水灌胃。术后第5,10,15天分别处死各组中的5只大鼠,取左肾行HE和M asson染色动态观察肾脏病理改变,并用免疫组化方法检测肾小管间质中NF-κB p65的动态表达。结果组织病理显示模型组呈现进行性肾间质面积增宽,纤维化程度加重。免疫组化结果显示假手术组大鼠肾组织中仅见极少部分的肾小球系膜细胞和肾皮质远曲小管上皮细胞表达较弱的NF-κB p65,主要位于细胞浆,各时间点的表达无明显差异。模型组大鼠肾NF-κB p65的表达主要位于肾近曲小管和远曲小管上皮细胞浆和核中,其中以胞核表达为多,表达量较假手术组明显增加(P<0.01),其表达随梗阻时间的延长逐渐增多。阿乐组肾小管间质中NF-κB p65虽较假手术组明显增加(P<0.01),但均较同期模型组有不同程度的减少(P<0.01)。结论UUO模型大鼠肾小管间质NF-κB的表达明显增加,阿托伐他汀可下调NF-κB的表达,其改善肾小管间质纤维化作用可能与抑制NF-κB的活性有关。

OBJECTIVE To observe the expression of NF-κB p65 at different periods in renal tubulointerstitium and the effect of atorvastatin on the expression of NF-κB p65 in unilateral ureteral obstruction （UUO） model rats. METHODS Forty-five female Sprague Dawley rats were divided into 3 groups , the sham-operated group, the model group and the atorvastatin group. The latter two groups underwent UUO and then received vehicle or atorvastatin （ 10mg · kg^-1· d^-1 ） by daily intragastric administration from three days before the UUO operation to the day of sacrifice. The sham-operated rats received vehicle. Five rats of each group were killed respectively at 5,10,15 days after surgery. Histological changes of renal tissue were observed by HE and Masson staining. Immunohistochemistry for NF-κB p65 was performed in renal tubulointerstitium at each time point. RESULTS The interstitial expansion and fibrosis of obstructed kidneys was prominent in the model group . Atorvasatin ameliorated interstitial expansion and fibrosis in Atorvastin group. NF-κB p65 were faintly stained in the sham-operated kidneys, mainly concentrated at glomerular mesangial cells and renal tubular epithelial cells. NF-κB p65 in renal tubulointerstitium increased progressively starting from 5 to 15 days in model group comparing with the sham-operated group （P 〈 0.01 ）, the atorvastatin group had less deposition of NF-κB p65 in renal tubulointerstitium comparing with the model group （P 〈 0.01 ）. CONCLUSION NF-κB p65 expression was increased progressively in the tubulointerstitium in UUO rats. Atorvastatin may play a protective role for the kidney by downregulating NF-κB and alleviating renal interstitial fibrosis in UUO rats.