基于PTEN/PI3K/Akt信号通路探讨糖通饮对糖尿病肾病大鼠足细胞损伤的保护作用  

Protective effects of Tangtongyin on podocyte injury in rats with diabetic nephropathy via PTEN/PI3K/Akt signaling pathway

作　　者：杨红[1] 潘艳伶 陈洪民 伏红颖 唐露 凌湘力 YANG Hong;PAN Yan-ling;CHEN Hong-min;FU Hong-ying;TANG Lu;LING Xiang-li(Guizhou Medical University,Guiyang 550004,China;The Hospital Affiliated to Guizhou Medical University,Guiyang 550004,China;West China Longquan Hospital Sichuan University,Chengdu 610000,China)

机构地区：[1]贵州医科大学,贵州贵阳550004 [2]贵州医科大学附属医院,贵州贵阳550004 [3]四川大学华西医院龙泉医院,四川成都610000

出　　处：《中成药》2024年第7期2182-2188,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(82060837);贵州省科技基金委员会合作计划项目(黔科合基础-ZK[2023]一般369号);2024年度贵州省中医药管理局中医药、民族医药科学技术研究专项课题(QZYY-2024-025);凌湘力全国名中医传承工作室建设项目(国中医药办人教函[2022]245号)。

摘　　要：目的探讨糖通饮对糖尿病肾病(DN)大鼠足细胞损伤的保护作用。方法高脂高糖饮食联合链脲佐菌素(STZ)多次注射建立DN大鼠模型,并随机分为模型组、厄贝沙坦组(13.5mg/kg)和糖通饮低、中、高剂量组(930、1860、3720mg/kg),另设置正常组,各组灌胃给予相应剂量药物,每天1次,连续8周。检测各组大鼠空腹血糖(FBG)、24h尿蛋白(24-hUP)、血肌酐(Scr)、血尿素氮(BUN)水平,HE染色观察各组大鼠肾组织病理形态学改变,透射电子显微镜观察肾足细胞超微结构变化,RT-qPCR法检测肾组织PTEN、PI3K、Akt、nephrin、podocin、CD2APmRNA表达,Westernblot法检测肾组织PTEN、PI3K、Akt、p-Akt、nephrin、podocin、CD2AP蛋白表达。结果与模型组比较,糖通饮各剂量组FBG、24-hUP、Scr、BUN水平降低(P<0.05,P<0.01),肾组织病理形态和足细胞超微结构得到改善,PTEN、nephrin、podocin、CD2APmRNA和蛋白表达升高(P<0.05,P<0.01),p-Akt蛋白表达降低(P<0.05,P<0.01);糖通饮中、高剂量组PI3K、AktmRNA和蛋白表达降低(P<0.05,P<0.01)。结论糖通饮对DN大鼠肾组织足细胞有保护作用,其机制可能与调节PTEN/PI3K/Akt信号通路有关。AIM To investigate the protective effects of Tangtongyin on podocyte injury in rats with diabetic nephropathy(DN).METHODS The DN rat models established by feeding of high⁃fat and high⁃sugar diet combined with multiple injections of streptozotocin(STZ)were randomly divided into the model group,the irbesartan group(13.5 mg/kg)and the low⁃dose,medium⁃dose and high⁃dose Tangtongyin groups(930,1860,3720 mg/kg),in contrast to those normal rats of the blank group.In the 8 weeks consecutive administration,each group was intragastrically dosed with the corresponding drug once daily.The rats had their fasting blood glucose(FBG),24⁃hour urine protein(24⁃h UP),serum creatinine(Scr)and blood urea nitrogen(BUN)levels detected;their renal pathological changes observed by HE staining;their ultrastructural changes of renal podocytesobserved by transmission electron microscopy;their mRNA expressions of renal PTEN,PI3K,Akt,nephrin,podocin and CD2AP detected by RT⁃qPCR;and their protein expressions of renal PTEN,PI3K,Akt,p⁃Akt,nephrin,podocin and CD2AP detected by Western blot.RESULTS Compared with the model group,the Tangtongyin groups displayed decreased levels of FBG,24⁃h UP,Scr and BUN(P<0.05,P<0.01);improved renal pathological morphology and podocyte ultrastructure;increased mRNA and protein expressions of PTEN,nephrin,podocin and CD2AP(P<0.05,P<0.01);and decreased expression of p⁃Akt protein(P<0.05,P<0.01).Additionally,the medium⁃dose and high⁃dose Tangtongyin groups shared indecreased mRNA and protein expressions of PI3K and Akt(P<0.05,P<0.01).CONCLUSION Tangtongyin can protect the renal podocytes in DN rats,and its mechanism may associate with its efficacy via PTEN/PI3K/Akt signaling pathway.

关 键 词：糖通饮 糖尿病肾病 足细胞 PTEN/PI3K/Akt信号通路 

分 类 号：R285.5[医药卫生—中药学]