尿毒康通过抑制p38/ERK MAPK通路改善UUO大鼠肾小管细胞上皮-间质转化

Niaodukang improves epithelial-mesenchymal transition of renal tubular epithelial cells in UUO rats by inhibiting p38/ERK MAPK pathway

关键词:  尿毒康  肾纤维化  丝裂原活化蛋白激酶信号通路

Key words:  Niaodukang  renal fibrosis  mitogen-activated protein kinase signaling pathway

摘要:

[目的] 研究尿毒康对肾纤维化大鼠肾功能及肾组织病理改变的影响，初步探讨尿毒康抗纤维化的作用机制。[方法] 采用单侧输尿管结扎法（UUO）复制大鼠肾间质纤维化模型。将大鼠按体质量分为假手术组，模型组，阳性药对照组（氯沙坦30 mg/kg，10 mL/kg），尿毒康20 mL/kg、10 mL/kg和5 mL/kg组。手术第2天即开始灌胃给予相应受试药物，1次/d，连续21 d。末次给药后测定24 h尿蛋白含量；检测血清肌酐（SCr）水平；剖取结扎侧肾脏（左肾），苏木精-伊红（HE）染色观察大鼠肾组织的病理改变情况；Masson染色观察纤维化程度并评分；实时定量聚合酶链反应（qRT-PCR）检测肾脏重组人转化生长因子-β（TGF-β）与α-平滑肌肌动蛋白（α-SAM）mRNA的表达水平；Western blot检测肾脏p38，细胞外信号调节蛋白激酶（ERK）蛋白表达水平。。[结果] 尿毒康能明显降低UUO模型大鼠SCr水平（P<0.01）和24 h尿蛋白定量水平（P<0.01）。尿毒康组病理表现较模型组有不同程度减轻，其中10 mL/kg组改善相对明显，并能明显抑制肾脏p38，ERK1/2蛋白的表达。。[结论] 尿毒康能明显改善UUO模型大鼠的肾功能，改善结扎侧肾小管细胞上皮-间质转化，且与抑制了p38/ERK丝裂原治化蛋白激酶（MAPK）相关。

Abstract:

[Objective] To study the effect of Niaodukang on renal function and pathological changes of renal tissue in rats with renal fibrosis,and to explore the mechanism of anti-fibrosis effect of Niaodukang.[Methods] Unilateral ureteral ligation (UUO) was used to replicate the rat renal interstitial fibrosis model. The model rats were divided into control group,model group,positive group (losartan,30 mg/kg,10 mL/kg),Niaodukang 20 mL/kg,10 mL/kg and 5 mL/kg groups according to their body weight. On the second day after the operation,the corresponding test drug was administered by intragastric administration once a day for 21 days. The 24 h urine protein content was measured after the last administration. Serum creatinine (SCr) level was detected. The kidney of the ligation side (left kidney) was dissected and the pathological changes of rat kidney tissue were observed by HE staining,Masson staining was used to observe the degree of fibrosis and score. The expression levels of TGF-β and α-SAM mRNA in kidney were detected by QRT-PCR. The expression level of p38 and ERK protein in kidney was detected by Western blot.[Results] Niaodukang can significantly reduce SCr level (P<0.01) and 24 hour urinary protein level (P<0.01) in UUO model rats. Compared with the model control group,the pathological manifestations in Niaodukang group were reduced to some extent,and the improvement in the 10 mL/kg group was relatively obvious,and the expression of P38 and ERK1/2 protein in kidney was obviously inhibited.[Conclusion] Niaodukang can obviously improve the renal function of UUO model rats and improve the mesenchymal transition of renal tubular epithelial cells on ligation side,which is related to the inhibition of p38/ERK MAPK.