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目的研究2型糖尿病肾间质纤维化中p38丝裂原激活蛋白激酶(p38MAPK)、Ⅲ型胶原蛋白(Col3)和Ⅳ型胶原蛋白(Col4)表达,及1,25-(OH)2-VD3对其表达的影响;探讨p38MAPK与Col3和Col4表达的相关性。方法以高糖高脂饮食联合30 mg/kg链脲佐菌素(STZ)诱导大鼠2型糖尿病模型。将60只大鼠随机平均分为对照组、模型组、1,25-(OH)_2-VD_3治疗组[建模后给予6 ng/(100g·d)1,25-(OH)_2-VD_3治疗]、胰岛素组(建模后给予2~3 U胰岛素治疗)。干预8周后检测4组血清肌酐(Scr)、血尿素氮(BUN)、24 h蛋白尿水平;过碘酸希夫反应(PAS)染色观察肾脏病变情况;采用Western blot及免疫组织化学染色检测大鼠肾间质p38MAPK、Col3和Col4的表达;采用Spearman法进行相关性分析。结果与模型组相比,1,25-(OH)_2-VD_3治疗组和胰岛素治疗组血清肌酐、尿素氮、24 h蛋白尿和肾间质受损面积均降低;与对照相比,模型组p38MAPK、Col3和Col4水平增加,1,25-(OH)_2-VD_3治疗组和胰岛素治疗组明显降低;相关性分析发现24 h蛋白尿与p38MAPK、Col3和Col4免疫组织化学的结果呈正相关,p38MAPK的表达与Col3和Col4表达呈正相关。结论 2型糖尿病大鼠肾间质组织p38MAPK、Col3和Col4表达上调,1,25-(OH)_2-VD_3可能通过p38MAPK下调Col3、Col4的表达改善糖尿病肾病肾组织纤维化。
Objective To investigate the expressions of p38 mitogen-activated protein kinase (p38MAPK), collagen type Ⅲ (Col3) and type Ⅳ collagen (Col4) in renal interstitial fibrosis in type 2 diabetic rats and the relationship between 1,25- (OH) On the expression of p38MAPK; Col3 and Col4 expression of the correlation. Methods High glucose and high fat diet combined with 30 mg / kg streptozotocin (STZ) induced type 2 diabetes in rats. Sixty rats were randomly divided into control group, model group and 1,25- (OH) 2-VD_3 treatment group [6ng / (100g · d) 1,25- (OH) 2-VD_3 Treatment], insulin group (2 ~ 3 U insulin treatment after modeling). Serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h proteinuria were measured at 8 weeks after intervention. Kidney lesions were observed by periodic acid Schiff (PAS) staining. Western blot and immunohistochemical staining Rat interstitial p38MAPK, Col3 and Col4 expression; Spearman correlation analysis. Results Compared with the model group, the serum creatinine, urea nitrogen, 24 h proteinuria and renal tubulointerstitial lesion area decreased in the 1,25- (OH) 2-VD_3 treatment group and the insulin treatment group. Compared with the control group, The levels of p38MAPK, Col3 and Col4 were significantly increased in the 1,25- (OH) 2-VD_3 treatment group and insulin treatment group. Correlation analysis showed that 24 h proteinuria was positively correlated with the results of p38MAPK, Col3 and Col4 immunohistochemistry, p38MAPK The expression of Col3 and Col4 was positively correlated. Conclusion The expressions of p38MAPK, Col3 and Col4 in renal interstitial tissue of type 2 diabetic rats are up-regulated. 1,25- (OH) 2-VD3 may reduce the renal fibrosis of diabetic nephropathy through the down-regulation of Col3 and Col4 expression by p38MAPK.