Effects of Bushen Huoxue Tang on Renal Function and JNK/p38 MAPK Signal Pathway in Rats with Mesangial Proliferative Glomerulonephritis
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摘要:
目的:探讨补肾活血汤对系膜增生性肾小球肾炎大鼠的肾功能及c-Jun 氨基末端激酶(JNK) /p38 丝裂原活化蛋白激酶(p38 MAPK) 信号通路的影响。方法:建立系膜增生性肾小球肾炎大鼠模型,56 只成功造模大鼠按随机数字表法分成4 组:模型组、缬沙坦组(10.3 mg/kg)、补肾活血汤低剂量组(5 g/kg)、补肾活血汤高剂量组(10 g/kg),每组14 只;另取14 只大鼠不做任何处理设为对照组;各药物组大鼠灌胃相应药物,模型组和对照组大鼠灌胃蒸馏水。给药4 周后,检测大鼠24 h 尿蛋白、血清肌酐(SCr)、尿素氮(BUN)、肾组织JNK、p38 MAPK 信使核糖核酸(mRNA) 和蛋白表达水平,苏木素伊红染色观察肾组织病理结构。结果:对照组肾小球结构正常;模型组可见明显弥漫性系膜细胞增生,伴大量中性粒细胞浸润,可见明显轻度纤维化;缬沙坦组及补肾活血汤高剂量组系膜细胞增生减少,内皮细胞轻度增生,中性粒细胞浸润减少;补肾活血汤低剂量组仍然可见肾小球肿胀增生。与对照组比较,模型组24 h 尿蛋白、血清SCr、BUN、肾组织JNK、p38 MAPK mRNA 和蛋白表达水平明显升高(P<0.05);与模型组比较,缬沙坦组和补肾活血汤低、高剂量组24 h 尿蛋白、血清SCr、BUN、肾组织JNK、p38MAPK mRNA 和蛋白表达水平明显降低(P<0.05),且补肾活血汤高剂量组24 h 尿蛋白、血清SCr、BUN、肾组织JNK、p38MAPK mRNA 和蛋白表达水平低于补肾活血汤低剂量组(P<0.05);补肾活血汤高剂量组和缬沙坦组上述指标差异无统计学意义(P>0.05)。结论:补肾活血汤对系膜增生性肾小球肾炎大鼠具有肾保护作用,可改善大鼠肾功能和肾组织病理反应,其机制可能与补肾活血汤抑制JNK、p38 MAPK mRNA 和蛋白的表达进而抑制JNK/p38 MAPK 信号通路的激活有关。
Abstract:
Abstract: Objective: To investigate the effects of Bushen Huoxue Tang on renal function and c-Jun amino terminal kinase(JNK)/p38 mitogen activated protein kinase(p38 MAPK) signal pathway in rats with mesangial proliferative glomerulonephritis. Methods:The rat model of mesangial proliferative glomerulonephritis was established. 56 successful rats model were randomly divided into 4 groups: model group, valsartan group(10.3 mg/kg), Bushen Huoxue Tang low dose group(5 g/kg) and Bushen Huoxue Tang high dose group(10 g/kg),with 14 rats in each group;another 14 rats were set as the control group without any treatment; rats in each drug group were gavaged with corresponding drugs, and rats in model group and control group were gavaged with distilled water. After 4 weeks of administration, the expression levels of 24 h urinary protein,serum creatinine(SCr),urea nitrogen(BUN),JNK,p38 MAPK messenger RNA(mRNA) and protein in renal tissue were detected, and the pathological structure of renal tissue was observed by hematoxylin eosin staining. Results: The glomerular structure of the control group was normal.In the model group, there was obvious diffuse mesangial cell proliferation with a large number of neutrophil infiltration and obvious mild fibrosis. Mesangial cell proliferation,endothelial cell proliferation and neutrophil infiltration decreased in valsartan group and Bushen Huoxue Tang high- dose group. Glomerular swelling and hyperplasia were still seen in the low- dose group of Bushen Huoxue Tang. Compared with the control group, the expression levels of 24 h urinary protein,serum SCr,bun,JNK,p38 MAPK mRNA and protein in renal tissue in the model group were significantly higher(P<0.05) .Compared with the model group, the expression levels of 24 h urinary protein,serum SCr,BUN,JNK,p38 MAPK mRNA and protein in valsartan group and Bushen Huoxue Decoction low and high dose groups were significantly lower(P<0.05), and the expression levels of 24 h urinary protein, serum SCr, BUN, JNK,p38 MAPK mRNA and protein in Bushen Huoxue Tang high dose group were lower than those in Bushen Huoxue Tang low dose group(P<0.05) .There was no significant difference in the above indexes between Bushen Huoxue Tang high-dose group and valsartan group(P>0.05). Conclusion:Bushen Huoxue decoction has renal protective effect on rats with mesangial proliferative glomerulonephritis,and can improve renal function and renal pathological reaction. Its mechanism may be related to Bushen Huoxue Tang inhibiting the expression of JNK,p38 MAPK mRNA and protein,and then inhibiting the activation of JNK/p38 MAPK signal pathway.