摘要：
ABSTRACT:OBJECTIVE To explore intervention of Gualou Qumai Tang(GLQM) in preventing the development of diabetic nephropathy(DN) through P38MAPK signaling pathway methods.METHODS Except those in the normal group,SD rats of DN model were established by with unilateral nephrectomy and intraperitoneal injection of streptozotocin(STZ)induced produc-tion.Then rats were randomly divided into five groups:the model group,and the four treated groups treated with low dose of GLQM-L,medium dose of GLQM-M,high dose of GLQM-H,positive medicine (valsartan),The treatments were given via gastrogavage every day starting from the 4th week of modeling,groups treated with high,medium and low dose of GLQM were given via gastrogavage to 5.6,2.8,1.4 g/kg,positive drugs(valsartan)group were given via gastrogavage to 4.8×10 -3 g/kg,the normal group and model group were given 2.8 g/kg distilled water,once a day for 12 weeks.we observed the sign of rats and the rat glomerular,renal tubular structure changes with the optical microscope.Then we observed the sign of rats and the expreion the basic fibroblast growth factor(bFGF),Insulin-like Growth Factor(IGF),Monocyte Chemotactic Protein-1 (MCP-1) changes in renal issues of rats by using ELISA.The protein expression of p-p38MPK,p-CREB,FN were immuno-histochemically investigated.The mRNA expressions FN in renal tissue we examined using qPCR method.The protein expres-sion of p-p38MPK,p-CREB,FN in renal tissue we also examined using Western Blot method.RESULTS The pathologic changes of the renal tissue apparented in the model group.The bFGF,IGF,MCP-1 in renal tissues of rats with model were higher than the nomal group,there were significant difference among the model group and the norml group(P <0.01).The bFGF,IGF,MCP-1 in renal tissues of rats with GLQM and valsartan were lower than the model group,there were significant difference among them(P <0.05~0.01).The protein expression of p-p38MAPK,p-CREB,FN in renal tissues with model were higher than the normal group(P <0.05~0.01).The mRNA expression of FN in renal tissues of rats with GLQM were lower than the model group(P <0.05~0.01);the protein expression of p-p38MAPK,p-CREB,FN in renal tissue of rats with GLQM were lower than the model group(P <0.05 ~0.01).CONCLUSION GLQM can reatrain the activation of p38MAPK signaling pathway and be effective in repair and regeneration of the damaged tissue,it is also slow down the process of DN.%目的：研究栝楼瞿麦汤干预糖尿病肾病大鼠 p38MAPK 炎症信号通路的机制,探讨其对糖尿病肾病的作用机制及治疗效果。方法通过对 SD 大鼠采用单侧肾切除及一次性腹腔注射链脲佐菌素(STZ)的方法构建大鼠糖尿病肾病(DN)模型。造模成功后,随机分为：DN 模型组,栝楼瞿麦汤高、中、低剂量组,阳性药物(缬沙坦)组,另设正常组。治疗组从实验开始第4周起,栝楼瞿麦汤高、中、低剂量组分别以5.6、2.8、1.4 g/kg ig,缬沙坦4.8×10-3 g/kg ig,正常组及模型组均给予2.8 g/kg 蒸馏水 ig,每日1次,连续12周。于末次给药12 h 后,剖杀取大鼠肾组织。观察大鼠一般情况；光镜观察大鼠肾小球、肾小管组织结构变化；ELISA 检测大鼠肾组织中碱性成纤维细胞生长因子(bFGF)、胰岛素生长因子(IGF)及单核细胞趋化蛋白-1(MCP-1)的含量；Western blot 法检测大鼠肾组织 p-p38、p-CREB、FN 蛋白表达情况。逆转录聚合酶链反应(qPCR)法检测大鼠肾组织 FNmRNA 基因表达情况。结果 DN 模型组大鼠与正常组大鼠比较,肾组织出现明显的病理变化,肾组织中 bF-GF、IGF、MCP-1含量显著升高(P <0.01)；p-p38MAPK、p-CREB、FN 蛋白表达水平显著上调(P <0.05)；FNmRNA 基因表达水平显著上升(P <0.05)。经栝楼瞿麦汤干预后,各治疗组与 DN 模型组比较,肾组织病理变化有不同程度的改善；肾组织中bFGF、IGF、MCP-1含量有不同程度的减少,差异具有统计学意义(P <0.05~0.01)；肾组织中 p-p38MAPK、p-CREB、FN 蛋白表达水平下调；FNmRNA 基因表达水平下调,差异具有统计学意义(P <0.05~0.01)。结论栝楼瞿麦汤能通过抑制 DN 大鼠肾组织中 p38MAPK 炎症信号通路的激活,使损伤的组织得以修复,从而延缓 DN 的病理进程。
