补肾活血汤对系膜增生性肾小球肾炎大鼠肾功能及JNK/p38 MAPK信号通路的影响  

Effects of Bushen Huoxue Tang on Renal Function and JNK/p38 MAPK Signal Pathway in Rats with Mesangial Proliferative Glomerulonephritis

作　　者：凌磊 张玮 裘琳琳 彭佳蓓 孙佳 LING Lei;ZHANG Wei;QIU Linlin;PENG Jiabei;SUN Jia

机构地区：[1]杭州市临平区第一人民医院药剂科,浙江杭州311100 [2]杭州市临平区第一人民医院肾内科,浙江杭州311100

出　　处：《新中医》2022年第9期29-33,共5页New Chinese Medicine

基　　金：浙江省中医药科学研究基金项目(2019ZB110)。

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。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 t

关 键 词：系膜增生性肾小球肾炎 补肾活血汤 大鼠 肾功能 c-Jun氨基末端激酶/p38丝裂原活化蛋白激酶信号通路 

分 类 号：R285.5[医药卫生—中药学]