1,25-二羟维生素D_3对大鼠肾间质纤维化的作用研究

目的：研究1,25-二羟维生素D3〔1,25-（OH）2D3〕对单侧输尿管梗阻（UUO）大鼠肾间质纤维化的影响。方法：45只大鼠随机分为假手术组（n=15）、UUO组（n=15）和1,25-（OH）2D3干预组（n=15）,建立UUO大鼠肾间质纤维化模型,干预组于术后第1天起每天腹腔注射1,25-（OH）2D3,假手术组及UUO组腹腔注射等量生理盐水。分别于术后第3天、第7天和第14天处死大鼠,每次5只,取梗阻侧肾脏行HE、Masson染色及α-平滑肌肌动蛋白（α-SMA）免疫组化标记,观察肾损伤程度和肾间质纤维化程度;取血测定肌酐和尿素氮水平观察肾功能;处死前1天收集24 h尿液,检测尿中蛋白含量。结果：与假手术组相比,UUO组和干预组各时间点HE、Masson染色和α-SMA表达变化明显,呈逐渐加重趋势,差异有统计学意义（P〈0.05）;肌酐、尿素氮及24 h尿蛋白含量术后第3和第7天时表现为升高,术后第14天时出现下降,差异有统计学意义（P〈0.05）。与UUO组相比,干预组各时间点各项指标变化明显改善,差异有统计学意义（P〈0.05）。结论：1,25-（OH）2D3可抑制UUO大鼠肾间质纤维化进程,改善肾功能。

The effects of 1, 25-dihydroxyvitamin D3 on interstitial fibrosis to kidney after unilateral ureteral obstruction in rats

Objective: To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on interstitial fibrosis to kidney after unilateral ureteral obstruction(UUO) in rats.Methods: 45 rats were randomly divided in to 3 groups: sham operated group(n=15) which was given 1,25-(OH)2D3 by intraperitoneal injection one day on post operative every day,UUO group(n=15) and 1,25-(OH)2D3 treatment group(n=15) which were all given normal saline by intraperitioneal injection equivalently.They were sacrificed at the 3rd,7th and 14th days respectively after UUO,every time for only 5.Interstitial fibrosis of obstructed kidney was graded according to HE and Masson staining.The expression of α-SMA was examined by immunohistochemistry.The samples blood were collected to detect the concentration blood serum creatinine and blood urea nitrogen.Daily urinary protein were determined in these rats one day before sacrificed.Results: The degree of interstitial impairment and fibrosis of obstructed kidney and the expression of α-SMA in the UUO group and treatment group were significantly higher than those in the sham operated group(all P<0.05).The blood serum creatinine,blood urea nitrogen and daily urinary protein in the UUO group and treatment group were increased at the 3rd and 7th days after UUO,but they were decreased at the 14th day(all P<0.05).Compared with UUO group,all which in treatment group were significantly decreased(all P<0.05).Conclusion: 1,25-(OH)2D3 can alleviate interstitial fibrosis and renal function in rats after UUO.