目的探讨活性维生素D3对进展性肾炎大鼠肾小管间质损伤的干预作用及对肾间质纤维化的影响。方法实验动物按数字随机表法分为假手术组、进展性肾炎组(模型组)、活性维生素D3干预组(治疗组),每组7只。除对照组外,均采用右肾切除并两次注射Ig G(OX-7)鼠抗人Thy1.1单克隆抗体制备进展性肾炎大鼠模型。活性维生素D3干预8 w后,检测各组大鼠24 h尿蛋白、血肌酐(Scr)、尿素氮(BUN)及电解质的变化,并观察肾组织病理改变。免疫荧光检测肾小管间质低氧诱导因子(HIF)-1α的表达,原位杂交检测肾小管间质结缔组织生长因子(CTGF)mRNA的表达。结果与模型组比较,活性维生素D3治疗不仅使HIF-1α、CTGF表达显著下调(P<0.05),还能使大鼠24 h尿蛋白、BUN明显降低(P<0.05),肾组织病理损害明显减轻。结论慢性低氧上调了HIF-1α及前纤维因子的表达,活性维生素D3可能通过明显降低进展性肾炎大鼠肾小管间质HIF-1α、CTGF的表达,减轻肾小管间质纤维化而发挥肾脏保护作用。
Objective To investigate the effects of 1,25-dihydroxyvitamin D3 on the tubulointerstitial fibrosis in a progressive model of rat glomerulonephritis .Methods Experimental rats were randomly divided into sham operation ( control ) , progressive nephritis ( model group), progressive nephritis group treated with 1,25-dihydroxyvitamin D3 (vitamin D3 treatment)groups.The progressive nephritis model was established by right nephrectomy and injection with IgG (OX-7) mouse monoclonal anti-Thy 1.1 antibody twice.Progressive nephritis rats were given 1, 25-dihydroxyvitamin D3 by intragastric administration for 8 w and then were sacrificed .The levels of serum creatinine (Scr), urine protein, blood urea nitrogen (BUN)and the levels of calcium and phosphorus were measured .The renal morphologic changes were evaluated by PAS stained sections .The expression of HIF-1αin tubulointerstitial was detected by immunofluorescence and the level of connective tissue growth factor (CTGF) was detected by in-situ hybridization.Results The expressions of HIF-1α, CTGF mRNA in tubu-lointerstitial were lower in vitamin D3 treatment group than those in model group (P<0.05).In addition, the levels of urine protein and BUN in vitamin D3 treatment group were significantly lower than those in model group (all P<0.05).Renal pathological injury was improved by vitamin D3 treatment.Conclusions Chronic hypoxia increases the expression of HIF-lαand fibrosis related factors .1,25-dihydroxyvita-min D3 may protect kidney by decreasing the expression of HIF-1αand CTGF in the progressive nephritis model rats .