吡咯烷二硫代氨基甲酸酯通过抑制核因子-κB信号通路改善UUO模型大鼠肾纤维化

Pyrrolidine Dithiocarbamate Improved Renal Fibrosis in UUO Model Rats by Inhibiting Nudear Factor-κB Signaling Pathway

目的探讨核因子抑制剂吡咯烷二硫代氨基甲酸酯(PDTC)对核因子-κB(NF-κB)P65、转化生长因子-β1(TGF-β1)表达的影响及对肾纤维化的作用。方法取60只SD成年大鼠,随机分为假手术组、模型对照组、早干预组和晚干预组。除假手术组,各组大鼠建立单侧输尿管结扎(UUO)模型,早干预组先给予PDTC 2 d,第3天开始建模。晚干预组建模开始后第2天给予PDTC。假手术组和模型对照组分别在建模开始后第2天给予等量蒸馏水。建模后第7、14、21天检测各组大鼠24 h尿蛋白定量及肾功能,检测血清NF-κB P65、TGF-β1水平的表达,Masson染色观察肾纤维化情况。结果在相同时间条件下,假手术组、模型对照组、早干预组、晚干预组24 h尿蛋白定量差异均无统计学意义(P均>0.05)。建模后第7、14、21天,与假手术组相比,模型对照组、早干预组、晚干预组血清肌酐、尿素氮、NF-κB P65、TGF-β1水平均升高(P均<0.05);与模型对照组相比,早干预组、晚干预组大鼠血清肌酐、尿素氮、NF-κB P65、TGF-β1水平均下降(P均<0.05)。建模后第21天,假手术组大鼠肾间质染色较少;模型对照组大鼠肾小管结构破坏明显,间质染色明显增多,有大量胶原形成;与模型对照组相比,早干预组和晚干预组大鼠肾间质纤维化程度有所减轻。结论 NF-κB抑制剂PDTC可通过抑制NF-κB P65表达减缓肾纤维化过程,减轻肾功能损伤情况。

Objective To observe the influences of nuclear factor inhibitor pyrrolidine dithiocarbamate(PDTC)on the expressions of nudear factor-κB P65(NF-κB P65),TGF-β1 and the effects of renal fibrosis.Methods sixty adult SD rats were randomly divided into four groups: sham operation group,model control group,early intervention group and late intervention group. Early intervention group was given PDTC 2 days before modeling,once a day. In addition to the sham operation group,other groups established UUO model.PDTC was given to the late intervention group on the second day after modeling,once a day. And the sham operation group and the model control group were given the same amount of distilled water respectively on the second day after modeling. On the 7 th,14 th and 21 st day after operation,the renal fibrosis was observed by Masson staining. The expression of NF-κB P65 and TGF-β1 in serum,the renal function and 24 h urine protein were detected. Results Under the same time condition,there was no significant difference in 24 h urine protein between sham operation group,model control group,early intervention group and late intervention group(P all>0.05). Compared with sham operation group,the level of serum creatinine,urea nitrogen,NF-κB P65 and TGF-β1 in model control group,early intervention group and late intervention group increased significantly on the 7 th,14 th and 21 st day(P all<0.05). Compared with model control group,the level of serum creatinine,urea nitrogen,NF-κB P65 and TGF-β1 in early intervention group and late intervention group decreased significantly(P all<0.05). All of the indexes in early intervention group and late intervention group were no significant difference(P>0.05). On the 21 st day after operation,the renal interstitium staining in the sham operation group was less. In the model control group the renal tubular structure was significantly damaged,the interstitium staining was significantly increased,and there was a lot of collagen formation. The changes in the early intervention group and the late intervention group were similar,but compared with the model control group,the blue area staining was less,and the degree of renal interstitial fibrosis was reduced. Conclusion PDTC,an inhibitor of NF-κB,can slow down the process of renal fibrosis and reduce the damage of renal function by inhibiting the expression of NF-κB P65.