肾安方对慢性肾脏病大鼠EGFR介导的PI3K/Akt通路的影响  

Effect of Shen’an Recipe(肾安方) on PI3K/Akt Pathway Mediated by EGFR in Rats with Chronic Renal Disease

作　　者：宋坚[1,2] 王旭东[1] 刘宏斌[1] 曹兴建[1] SONG Jian;WANG Xudong;LIU Hongbin;CAO Xingjian(Nantong First People's Hospital,Nantong Jiangsu 226000,China;Nanjing University Of Chinese Medicine,Nanjing Jiangsu 210046,China)

机构地区：[1]南通市第一人民医院,江苏南通226000 [2]南京中医药大学,江苏南京210046

出　　处：《中医药导报》2022年第8期22-26,共5页Guiding Journal of Traditional Chinese Medicine and Pharmacy

摘　　要：目的:观察肾安方对慢性肾脏病(CKD)大鼠生化指标和表皮生长因子受体(EGFR)介导的PI3K/Akt通路的影响,探讨其对慢性肾脏病的保护机制。方法:48只大鼠随机分为正常组12只和造模组36只,造模组大鼠采用腺嘌呤诱导法复制CKD模型,造模成功的30只大鼠随机分为模型组、肾安方组、羟苯磺酸钙组各10只。肾安方组大鼠以肾安方24.1 g/(kg·d)灌胃,羟苯磺酸钙组以羟苯磺酸钙100 mg/(kg·d)灌胃处理。模型组和正常组大鼠给予等体积生理盐水灌胃,给药4周后,检测各组大鼠血清尿素氮(BUN)、肌酐(Scr)、24 h尿蛋白(24 h UTP)、甲状腺激素(PTH)、β2微球蛋白(β2-MG)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1);HE染色和Masson染色观察肾脏病理变化程度;Real-time PCR法检测大鼠肾组织中EGFR mRNA、Akt mRNA、PI3K mRNA表达水平;Western blotting法检测EGFR/Akt/PI3K信号通路关键蛋白的表达水平。结果:与模型组比较,肾安方组、羟苯磺酸钙组BUN、Scr、PTH、β2-MG、24 h UTP、IL-6、TNF-α、TGF-β1、p-EGFR、p-PI3K,p-Akt及肾脏纤维化程度显著降低(P<0.05);肾安方组上述指标改善情况均优于羟苯磺酸钙组(P<0.05)。结论:肾安方可能通过抑制EGFR磷酸化,抑制PI3K/Akt通路的激活,减少TGF-β1的含量,从而减缓肾脏纤维化的进程。Objective:To observe the effects of Shen’an Recipe on biochemical indexes and PI3K/Akt pathway mediated by EGFR in rats with chronic kidney disease(CKD),and to explore its protective mechanism on chronic kidney disease.Methods:48 rats were divided into blank group and modeling group,with 12 in blank group and 36 in modeling group.The rats in the modeling group were induced by adenine to replicate the CKD model.30 successful rats were randomly divided into the model group,Shen’an Recipe group and calcium dobesilate group,with 10 rats in each group.The rats in the Shen’an Recipe group were given Shen’an Recipe 24.1 g/(kg·d) by gavage,and the rats in the calcium dobesilate group were given calcium dobesilate100 mg/(kg·d) by gavage.The rats in model group and normal group were given equal volume normal saline by gavage.After 4 weeks of administration,urea nitrogen(BUN),creatinine(Scr),24 hour urine protein(24 h UTP),thyroid hormone(PTH),β2 microglobulin(β2-mg),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and transforming growth factor-β1(TGF-β1) in serum were detected in each group.He staining and Masson staining were used to observe the degree of renal pathological changes.The expression levels of EGFR mRNA,Akt mRNA and PI3K mRNA were detected by Real-time PCR.Western blotting was used to detect the expression level of key proteins of EGFR/Akt/PI3K signaling pathway.Results:Compared with the model group,the BUN,Scr,PTH,β2-mg,24 h UTP,IL-6,TNF-α,TGF-β1,p-EGFR,p-PI3K,p-Akt and renal fibrosis were significantly decreased(P<0.05).The improvement of the above indexes in Shen’an Recipe group was better than that in calcium dobesilate group(P<0.05).Conclusion:Shen’an Recipe may reduce the content of TGF-β1 by inhibiting the phosphorylation of EGFR and the activation of PI3K/Akt pathway,thus slowing down the process of renal fibrosis.

关 键 词：慢性肾脏病 肾脏纤维化 肾安方 表皮生长因子受体 PI3K/AKT通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]