黄连解毒汤对脂多糖诱导的小鼠急性肾损伤治疗作用及机制  

Effect and mechanism of Huanglian Jiedu Decoction on lipopolysaccharideinduced acute kidney injury in mice

作　　者：熊致立 王瑞 朱晓云 付彤飞 李成银 吴俊松 王林群 沈银峰 巴元明 XIONG Zhili;WANG Rui;ZHU Xiaoyun;FU Tongfei;LI Chengyin;WU Junsong;WANG Linqun;SHEN Yinfeng;BA Yuanming(Clinical College of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430000,China;Hubei Institute of Traditional Chinese Medicine,Affiliated Hospital of Hubei University of Chinese Medicine,Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430000,China)

机构地区：[1]湖北中医药大学中医临床学院,湖北武汉430000 [2]湖北省中医院,湖北中医药大学附属医院,湖北省中医药研究院,湖北武汉430000

出　　处：《中草药》2024年第3期853-860,共8页Chinese Traditional and Herbal Drugs

基　　金：2022年湖北省科技重大专项课题(2022ACA003-03);巴元明全国名老中医药专家传承工作室项目(国中医药人教函[2022]75号);湖北省自然科学基金资助项目(2022CFD023,2023AFD149);湖北省中医药管理局2023~2024年度中医药科研项目(ZY2023Z001)。

摘　　要：目的研究黄连解毒汤对脂多糖诱导的小鼠急性肾损伤的作用及作用机制。方法雄性C57BL/6小鼠随机分为对照组、模型组和黄连解毒汤低、中、高剂量(50、100、150 mg/kg)组,每组8只。连续ig黄连解毒汤3 d,末次给药2 h后,ip脂多糖(10 mg/kg)建立急性肾损伤模型。检测血清中肌酐和尿素氮水平;苏木素-伊红(HE)和高碘酸-席夫(PAS)染色检测肾组织病理变化;免疫组化法检测肾组织B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)和Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)表达;TUNEL染色检测肾组织细胞凋亡情况;Western blotting检测肾组织磷酸酯酶与张力蛋白同源物(phosphatase and tensin homolog,PTEN)、磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、蛋白激酶B(protein kinase B,Akt)、p-PI3K和p-Akt蛋白表达。结果黄连解毒汤明显降低急性肾损伤小鼠血清中尿素氮及肌酐水平(P<0.01、0.001),改善肾脏组织病理变化,抑制肾组织细胞凋亡,上调肾组织PI3K、Akt蛋白表达(P<0.05),下调PTEN、p-PI3K、p-Akt蛋白表达(P<0.05)。结论黄连解毒汤通过调控PTEN/PI3K/Akt通路抑制细胞凋亡,进而缓解急性肾损伤。Objective To study the effect and mechanism of Huanglian Jiedu Decoction(黄连解毒汤)on lipopolysaccharide-induced acute kidney injury in mice.Methods Male C57BL/6 mice were randomly divided into control group,model group,Huanglian Jiedu Decoction low-,medium-and high-dose(50,100,150 mg/kg)groups,with eight mice in each group,after continuous administration of Huanglian Jiedu Decoction for 3 d,an acute kidney injury model was established with ip lipopolysaccharide(10 mg/kg)2 h after the last administration.Levels of creatinine and urea nitrogen in serum were detected.Hematoxylin-eosin(HE)and periodate-schiff(PAS)staining were used to detect pathological changes in renal tissues.Immunohistochemical assay was used to detect expressions of B-cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax)in renal tissues.TUNEL staining was used to detect cell apoptosis of renal tissues.Western blotting was used to detected the protein expressions of phosphatase and tensin homolog(PTEN),phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),p-PI3K and p-Akt in renal tissues.Results Huanglian Jiedu Decoction significantly reduced the levels of urea nitrogen and creatinine in serum of mice with acute kidney injury(P<0.01,0.001),improved the pathological changes of kidney,inhibited cell apoptosis in renal tissue,up-regulated the protein expression levels of PI3K and Akt(P<0.05),and down-regulated the protein expression levels of PTEN,p-Akt and p-PI3K(P<0.05).Conclusion Huanglian Jiedu Decoction can inhibit cell apoptosis by regulating PTEN/PI3K/Akt pathway,thereby alleviating acute kidney injury.

关 键 词：黄连解毒汤 急性肾损伤 炎症反应 细胞凋亡 磷酸酯酶与张力蛋白同源物/磷脂酰肌醇3-激酶/蛋白激酶B通路 咖啡酸 小檗碱 黄芩素 

分 类 号：R285.5[医药卫生—中药学]