基于EGFR/PI3K/Akt信号通路探讨黄连-麦冬药对延缓糖尿病肾病的作用机制  

Mechanism of Action of Coptidis Rhizoma and Ophiopogonis Radix in Delaying Diabetic Nephropathy Based on EGFR/PI3K/Akt Signaling Pathway

作　　者：李少玉 龚曼[1,2] 李秋芳[4] 代丽萍[1,3] 王桂群 杨秋琛 张琼琼 许二平[1,2] 刘雅琳[1,3] LI Shaoyu;GONG Man;LI Qiufang;DAI Liping;WANG Guiqun;YANG Qiuchen;ZHANG Qiongqiong;XU Erping;LIU Yalin(Henan Collaborative Innovation Center for Research and Development on the Whole Industry Chain of Yu-Yao,Henan University of Chinese Medicine,Zhengzhou 450046,China;Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,China;School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学豫药全产业链研发河南省协同创新中心,郑州450046 [2]河南中医药大学中医药科学院,郑州450046 [3]河南中医药大学药学院,郑州450046 [4]郑州大学第三附属医院生殖健康医院,郑州450046

出　　处：《中国实验方剂学杂志》2024年第20期22-29,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82274496);河南省科技创新项目(212102311087);河南中医药大学博士科研基金项目(BSJJ2022-06)。

摘　　要：目的:观察黄连-麦冬药对对糖尿病肾病(DN)大鼠肾组织损伤及表皮生长因子受体(EGFR)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响,探讨其延缓DN可能的作用机制。方法:将36只雄性Wistar大鼠随机分为正常组6只和造模组30只,造模组采用高脂高糖饲料喂养联合链脲佐菌素(STZ)共同诱导的方法建立2型糖尿病大鼠模型,模型制备成功后随机分为模型组、黄连-麦冬低、中、高剂量组(100、200、400 mg·kg^(-1))和二甲双胍组(200 mg·kg^(-1))。给药后检测大鼠空腹血糖(FBG)、24 h尿蛋白(24 h-UTP)、肌酐(SCr)、尿素氮(BUN)、尿酸(UA)水平;苏木素-伊红(HE)染色和马松(Masson)染色观察大鼠肾组织病理变化;蛋白免疫印迹法(Western blot)、实时荧光定量聚合酶链式反应(Real-time PCR)检测各组大鼠肾组织EGFR、PI3K、Akt相关蛋白表达及其mRNA表达水平。结果:与正常组比较,模型组大鼠FBG、SCr、BUN、UA、24 h-UTP和肾脏指数显著升高(P<0.01),肾小管上皮细胞大量坏死,肾小球内胶原蛋白含量显著升高(P<0.01);与模型组比较,各给药组大鼠上述指标均有不同程度的改善。黄连-麦冬各剂量组和二甲双胍组大鼠FBG、SCr、BUN、UA、24 h-UTP、肾脏指数明显下降(P<0.05,P<0.01),肾小管上皮细胞坏死程度减轻,纤维化面积减少(P<0.01),EGFR、PI3K、Akt相关蛋白表达和mRNA表达明显上升(P<0.05,P<0.01)。结论:黄连-麦冬药对能够缓解DN大鼠肾组织损伤,其机制可能与调控EGFR/PI3K/Akt信号通路有关。Objective:To observe the effect of Coptidis Rhizoma and Ophiopogonis Radix on renal tissue injury and epidermal growth factor receptor(EGFR)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway in rats with diabetic nephropathy(DN)and explore its possible mechanism of delaying DN.Method:Thirty-six male Wistar rats were randomly divided into a normal group(6 rats)and a model group(30 rats).The model group was fed with a high-fat and high-sugar diet combined with streptozotocin(STZ)to establish a rat model of type 2 diabetes.After the successful preparation of the model,the rats were randomly divided into the model group,low,medium,and high dose groups of Coptidis Rhizoma and Ophiopogonis Radix(100,200,400 mg·kg^(-1)),and metformin group(200 mg·kg^(-1)).After administration,the levels of fasting blood glucose(FBG),24 h urine protein(24 h-UTP),creatinine(SCr),urea nitrogen(BUN),and uric acid(UA)were detected.Hematoxylin-eosin(HE)staining and Masson staining were used to observe the pathological changes of renal tissue in rats.Western blot and Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)were used to detect the related protein expression of EGFR,PI3K,and Akt and their mRNA expression levels in the renal tissue of rats in each group.Results:Compared with the normal group,the levels of FBG,SCr,BUN,UA,24 h-UTP,and kidney index in the model group were significantly increased(P<0.01),most renal tubular epithelial cells were necrotic,and the content of collagen in glomeruli was significantly increased(P<0.01).Compared with the model group,the above indexes of rats in each administration group were improved to varying degrees.The FBG,SCr,BUN,UA,24 h-UTP,and kidney index of rats in each dose group and metformin group were significantly decreased(P<0.01,P<0.05).The necrosis degree of renal tubular epithelial cells was reduced,and the fibrosis area was decreased(P<0.01).There related protein and mRNA expressions of EGFR,PI3K,and Akt were significantly increased(P<0.05,P<0.

关 键 词：黄连 麦冬 2型糖尿病 糖尿病肾病 表皮生长因子受体(EGFR)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R289R33