1,25(OH)_2D_3对脂多糖诱导的小鼠蛋白尿的影响

The inhibitive effects of 1,25(OH)_2D_3 on lipopolysaccharide-induced proteinuria in mice

目的观察1,25(OH)2D3对脂多糖诱导的小鼠蛋白尿和uPAR表达的影响。方法 24只C57BL/6雄性小鼠随机分为正常对照组(Sham组)、脂多糖(LPS)处理组(LPS组)、LPS与1,25(OH)2D3共同处理组[LPS+1,25(OH)2D3)组]。LPS组及LPS+1,25(OH)2D3组腹腔注射LPS 300μg(第1天200μg,第2天100μg),Sham组给予等量生理盐水腹腔注射,LPS+1,25(OH)2D3组提前2 d给予1,25(OH)2D32.5μg/(kg·d)灌胃,Sham组及LPS组每天给予等量橄榄油灌胃。第3天留取尿液后处死小鼠。结果 (1)Sham组、LPS组、LPS+1,25(OH)2D3组的尿蛋白分别为(72.0±35.6)、(732.9±233.2)、(412.3±82.7)μg/mg,LPS组尿蛋白比Sham组明显升高(P=0.000);LPS+1,25(OH)2D3组与LPS组相比,尿蛋白明显减少(P=0.001)。(2)LPS组足细胞uPAR蛋白及PLAUR mRNA的表达均高于Sham组和LPS+1,25(OH)2D3组(P<0.05)。结论 1,25(OH)2D3可能通过抑制uPAR的表达,减少蛋白尿。

Objective To investigate the effect of 1,25 （OH）2 D3 on the lipopolysaccharide （LPS） - induced pro- teinuria of mouse in vivo. Methods Twenty - four C57BL/6 male mice were randomly divided into three groups ： normal Sham group （Sham group）, LPS induced group （LPS group） and 1,25 （OH）2D3 treated group （Treatment group）. Intra- peritoneally injection of LPS （first day 200 μg, second day 100 μg） was given to the subjects in LPS group and Treatment group, while replaced LPS - free saline was given in Sham group. The 1,25 （OH） 2 D3 [ 2. 5 μg/（ kg. d） for 2 days ] lav- age was given to the subjects in Treatment group, 2 days before LPS injection. The 24 - hour urine after LPS injection was collected. All subjects were sacrificed on the third day. Results The proteinuria were （ 72.0 ± 35.6 ）, （ 732. 9 ± 233.2） and （412. 3 ±82. 7） μg/mg in Sham group, LPS group and Treatment group, respectively; while significant differences were revealed among them. Meanwhile, the uPAR expression was significantly increased in LPS group, which was inhibited by 1,25 （OH）2D3 in both protein level and mRNA level in Treatment group. Conclusion LPS -induced proteinuria can be alleviated by 1,25 （OH）2 D3 via inhibiting uPAR expression.