基于PI3K/Akt/NF-κB信号通路探讨高尿酸血症合并非酒精性脂肪肝机制  

Mechanism of hyperuricemia combined with nonalcoholic fatty liver based on the PI3K/Akt/NF-κB signaling pathway

作　　者：龚晓红 李松伟 李桓[1,3] 武上雯[3] 陆超群 陈一鸣 GONG Xiaohong;LI Songwei;LI Huan;WU Shangwen;LU Chaoqun;CHEN Yiming(Henan University of Chinese Medicine,Zhengzhou 450046;China.2.Henan Provincial Hospital of Chinese Medicine(the Second Affiliated Hospital of Henan University of Chinese Medicine),Zhengzhou 450002;.3.the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000;.4.Jiangsu Province Siyang Kangda Hospital,Suqian 223798)

机构地区：[1]河南中医药大学,郑州450046 [2]河南省中医院(河南中医药大学第二附属医院),郑州450002 [3]河南中医药大学第一附属医院,郑州450000 [4]江苏省泗阳康达医院,江苏宿迁223798

出　　处：《中国比较医学杂志》2023年第11期10-16,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81874465);河南省自然科学基金(222300420228);中医药科学研究专项课题(20-21ZYZD16,2022ZY1015,2021JDZY010);河南中医药大学科研创新项目(2021KYCX003);河南省科技攻关项目(222102310392);河南省科技计划联合基金项目(222301420089);河南省中医药拔尖人才项目(2022ZYBJ10)。

摘　　要：目的基于PI3K/Akt/NF-κB信号通路研究高尿酸血症合并非酒精性脂肪肝(HUA-NAFLD)的发病机制。方法64只SD大鼠,随机分为空白组、高尿酸血症(HUA)组、非酒精性脂肪肝(NAFLD)组、HUA-NAFLD组,每组16只,分别于8、12周末取材,对大鼠血清生化指标进行检测;苏木素-伊红(HE)和油红O染色法观察肝组织病理变化和脂质沉积情况;蛋白免疫印迹(Western blot)法对肝组织PI3K/Akt和NF-κB信号通路中相关蛋白进行检测。结果与其余三组比较,HUA-NAFLD组大鼠肝指数明显升高(P<0.05),肝细胞出现大量脂肪空泡,肝索结构模糊,肝组织病变更重。与空白组比较,NAFLD组高密度脂蛋白(HDL)水平降低,HUA组尿酸(UA)、低密度脂蛋白(LDL)水平升高,HUA-NAFLD组HDL水平降低,总胆固醇(TC)、UA、LDL甘油三酯(TG)水平升高(P<0.05);与HUA组比较,NAFLD组肌酐(UREA)水平降低(P<0.05);与HUA-NAFLD组比较,HUA组TC、TG、LDL水平降低,NAFLD组UA、TG、LDL降低(P<0.05)。Western blot结果显示,与空白组比较,NAFLD组AKT、p65磷酸化水平显著升高,HUA-NAFLD组AKT、PI3K、p65、IκκB磷酸化水平显著升高(P<0.05);与HUA-NAFLD组比较,HUA、NAFLD组AKT、p65磷酸化水平显著下降,HUA组IκκB磷酸化水平显著下降(P<0.05);与HUA组比较,NAFLD组p65磷酸化水平显著升高(P<0.05)。结论HUA-NAFLD组较单个疾病组生化指标异常更加明显,肝病变程度更重,PI3K/Akt/NF-κB信号通路可能在HUA、NAFLD,以及HUA-NAFLD发病过程中发挥重要作用。ObjectiveTo study the pathogenesis of hyperuricemia combined with nonalcoholic fatty liver disease(HUA-NAFLD)based on the PI3K/Akt/NF-κB signaling pathway.MethodsSixty-four SD rats were randomly divided into blank,HUA,NAFLD and HUA-NAFLD groups with 16 rats in each group.Samples were collected at weeks 8 and 12.Serum biochemical indexes were measured.Pathological changes and lipid deposition in liver tissue were observed by hematoxylin-eosin staining and oil red O staining.Relevant proteins in PI3K/Akt and NF-κB signaling pathways in liver tissues were measured by Western blot.ResultsCompared with the other three groups,the liver index of rats in the HUA-NAFLD group was increased significantly(P<0.05)with a large number of fat vacuoles in hepatocytes,s blurred structure of the hepatic cord,and more severe liver histopathology.Compared with the blank group,UA and LDL levels in the HUA group were increased,HDL levels in the NAFLD group were decreased,UA,TC,TG and LDL levels in the HUA-NAFLD group were increased,and HDL levels were decreased(P<0.05).Compared with the HUA-NAFLD group,TC,TG,and LDL levels were decreased in the HUA group,and UA,TG,and LDL levels in the NAFLD group were decreased(P<0.05).Compared with the blank group,AKT and p65 phosphorylation levels in the NAFLD group were increased significantly,AKT,PI3K,p65 and IκκB phosphorylation levels in the HUA-NAFLD group were increased significantly.Compared with the HUA-NAFLD group,AKT and p65 phosphorylation levels in the HUA-NAFLD group were decreased significantly(P<0.05).The IκκB phosphorylation level was decreased significantly in the HUA group.Compared with the HUA group,the p65 phosphorylation level in the NAFLD group was significantly increased(P<0.05).Conclusions Compared with the single disease group,the HUA-NAFLD group had more abnormal biochemical indexes and more severe liver lesions.The PI3K/Akt/NF-κB signaling pathway might play a major role in the pathogenesis of HUA,NAFLD and HUA-NAFLD.

关 键 词：高尿酸血症 非酒精性脂肪肝 PI3K/AKT信号通路 NF-ΚB信号通路 

分 类 号：R-33[医药卫生]