骨化三醇对单侧输尿管梗阻大鼠肾的保护作用

Effects of 1,25(OH)_(2) vitamin D_3 on interstitial fibrosis in unilateral ureteric obstruction rats

目的:探讨骨化三醇[1,25(OH)2D3]对单侧输尿管梗阻大鼠肾的保护作用。方法:24只雄性6周龄SD大鼠,建立单侧输尿管梗阻(UUO)模型,并分为四组:①治疗组6只,1,25(OH)2D3溶于无水乙醇中腹腔注射,3ng/(100 g.d)。②无水乙醇对照组6只,等容积无水乙醇腹腔注射。③空白对照组6只,仅行左侧输尿管结扎术。④假手术组6只。于第7天处死各组大鼠,采用光镜和RT-PCR观察肾组织纤维化和核因子-κB(NF-κB)表达的变化。结果:①UUO模型第7天时大鼠肾组织NF-κB明显升高,采用1,25(OH)2D3治疗后,肾组织NF-κB的异常升高能得到有效抑制,肾组织炎性细胞浸润明显减少。②治疗组大鼠肾间质纤维化程度较空白对照组和无水乙醇对照组明显减轻。结论:1,25(OH)2D3具有阻抑慢性肾疾病进行性发展的潜能,而这一作用与其能有效降低肾组织NF-κB的异常升高和减少肾组织炎性细胞浸润有一定关系。

Objective： To investigate the effects of 1,25 （OH）2 D3 on renal interstitial fibrosis in rats. Methods： Male SD rats （7 weeks old） were divided into 4 groups at random： ①the treatment group （6 rats） ： Unilateral ureteric obstruction （UUO） ＋ 1,25 （OH） 2 D3 3 ng/100 g body wt/day intraperitoneally （ I. P）, ②the control group（6 rats） ： UUO ＋ ethanol by I. P, ③UUO group（6 rats）, ④sham operated group（6 rats）. Kidneys were harvested at day 7 after UUO. Fibrosis was assessed by measuring tissue hydroxyproline content. Tissue NF-kB expression was determined by RT-PCR. Results： UUO for 7 days significantly activated NF-kB, induced interstitial fibrosis in obstructed kidneys in the control group and UUO group compared with sham operated group rats. Conversely daily administration of 1,25（OH）2D3 significantly inhibited NF-kB expression, inflammatory cell infiltration and decreased interstitial fibrosis in obstructed kidneys in the treatment group. Conclusion： 1,25 （OH）2D3 had beneficial effects on interstitial fibrosis in SD rats with UUO, and this effect may be associated with 1,25 （OH）2D3 inhibits NF-kB expression and inflammatory cell infiltration.