p38 MAPK、NF-κB在肾小管间质纤维化中的作用研究

Experimental study of the role of p38 MAPK and NF-_KB in fibrosis of renal tubular interstitium.

目的：探讨p38MAPK、NF-κB在单侧输尿管梗阻(UUO)大鼠肾小管间质纤维化发生中的作用。方法：将30只雌性SD大鼠随机分为假手术组及模型组。模型组行UUO术。术后第5、10、15d分别处死两组中的5只大鼠．取左肾行HE和Masson染色。并用免疫组化方法检测肾小管间质中TGF-β1、p38MAPK、P- p38MAPK、NF-κB的表达。结果：HE和Masson染色显示模型组大鼠肾小管间质增宽．小管间质细胞增多,小管基底膜增厚皱缩纤维化,随时间进展,病变愈加明显(P＜0．01)。免疫组化结果显示：似手术组大鼠肾小管间质中仅有少量TGF-β1、p38MAPK、P-p38MAPK、NF-κB表达；模型组大鼠梗阻侧肾小管间质中TGF-β1、p38MAPK、P-p38MAPK、NF-κB表达明显增加(P＜0．01)。结论：p38MAPK、NF-κB可能参与UUO大鼠肾小管间质纤维化过程。

Objective:To observe the expression of TGF-β1 .p38MAPK,P-p38MAPK and NF-κB in renal tubu- lar interstitium of unilateral urethra obstruction in (UUO) rats.so as to study the role of p38MAPK and NF-κB in renal tubular interstitium fibrosis (TIF).Methods:Thirty female Sprague-Dawley rats were divided into two groups,the sham-operated group and the model group.The left ureter was ligated to produce complete obstrac- tion.In the sham-operated group the left ureter was only isolated from neighboring tissue without undergoing ob- struction,five rats of each group were sacrificed on 5,10,15 days after surgery.Histological changes in renal tu- bular interstitium were observed with HE and Masson staining,Immunohistochemistry was performed on left re nal tubularfor assesting expression of TGF-β1,p38MAPK,P-p38MAPK and NF-κB in renal tubular interstitium was carried out at each time point.Results:The pathological features with HE staining and Masson's trichrome—staining included prominent interstitial expansion and fibrosis of the kidney with the obstructed ureter in the UUO rats(P＜0.01).TGF-β1,p38MAPK,P-p38MAPK and NF-κB were faintly stained in renal tubular interstitium in the sham-operated kidneys,but their expression was progressively up-regulated from 5 days to after UUO(P＜0.01).Conclusions:The expression of p38MAPK and NF-κB in renal tubular interstitium of UUO rats was in- creased significantly,and p38MAPK and NF-κB may play a role in the pathogenesis of kidney fibrosis.