1,25-二羟维生素D3对糖尿病肾病大鼠肾小管上皮细胞转分化的影响

目的研究1,25-二羟维生素D3对糖尿病肾病大鼠肾小管上皮细胞转分化的影响及其可能机制。方法 28只SD大鼠随机分为正常对照组(N组,8只)、糖尿病肾病模型组(M组,10只)、1,25-二羟维生素D3干预组(D组,10只)。检测各组大鼠24-h尿蛋白(24-h Upro)、血尿素氮(BUN)、血清肌酐(SCr)水平,HE染色观察肾组织病理学变化,应用免疫组化、RT-PCR方法分别检测大鼠肾组织α-平滑肌肌动蛋白(α-SMA)和上皮细胞钙黏素(E-cad)的蛋白及其mRNA的表达。结果与N组相比,M组大鼠肾小管间质损伤加重,24-h Upro及SCr水平、α-SMA蛋白及mRNA表达增加,E-cad蛋白和mRNA表达减少(P<0.05);而D组能明显逆转M组上述各观察指标的改变过程(P<0.05)。结论 1,25-二羟维生素D3可能通过下调糖尿病肾病大鼠肾组织α-SMA表达,上调E-cad表达,从而抑制肾小管上皮细胞转分化,减轻肾小管间质病理损伤而发挥其肾脏保护作用。

Effects of 1,25-dihydroxy-vitamin D3 on transdifferentiation of renal tubular epithelial cells in rats with diabetic nephropathy

Objective To investigate the effect and possible mechanism of 1,25-dihydroxy-vitamin D3 on the transdifferentiation of renal tubular epithelial cells in rats with diabetic nephropathy(DN).Methods Twenty-eight SD rats were randomly divided into three groups of N(normal controls,8 rats),M(streptozotocin-induced DN model,10 rats) and D(DN model rats treated with 1,25-dihydroxyvitamin D3).The levels of 24-hours urinary protein(24 h Upro),blood urea nitrogen(BUN) and serum creatinine(SCr) were measured,and the pathological changes of kidney tissues were observed by HE staining.The protein and mRNA expressions of α-smooth muscle actin(α-SMA) and E-cadherin(E-cad) in the kidney were detected by immunohistochemistry and RT-PCR,respectively.Results Compared with group N,the injury of renal tubular interstitium was more serious,the levels of 24-h Upro and SCr and the protein and mRNA expressions of α-SMA were increased,whereas the protein and mRNA expressions of E-cad were decreased in group M(P<0.05),which were all significantly reversed in group D(P<0.05).Conclusion 1,25-Dihydroxyvitamin D3 has a protective effect on the kidney of rats with DN,which may be related to that 1,25-dihydroxy-vitamin D3 can inhibit the transdifferentiation of renal tubular epithelial cells and mitigate the pathological injury of renal tubular interstitium via down-regulation of α-SMA expression and up-regulation of E-cad expression.