载脂蛋白A1在非酒精性脂肪肝炎相关慢性肾损伤中的表达及作用  

Expression and role of apolipoprotein A1 in non-alcoholic steatohepatitis-related chronic kidney injury

作　　者：袁玥 陈琳[1] 王文姬[1] 李雪竹 Yuan Yue;Chen Lin;Wang Wenji;Li Xuezhu(Department of Nephrology,Shanghai Ninth People's Hospital Affiliated to Medical College,Shanghai Jiaotong University,Shanghai,200011,P.R.China)

机构地区：[1]上海交通大学医学院附属第九人民医院肾内科,上海200011

出　　处：《老年医学与保健》2024年第2期461-468,476,共9页Geriatrics & Health Care

基　　金：国家自然科学基金面上项目(81970622)。

摘　　要：目的探讨非酒精性脂肪肝炎(NASH)相关慢性肾脏损伤中载脂蛋白A1(apoA1)的表达及作用。方法采用由西式高热量饮食联合小剂量四氯化碳(CCl_(4))腹腔注射诱导建立NASH模型,以正常饮食和单独CCl_(4)腹腔注射为对照,检测肾功能、肾脏组织病理学改变,血清apoA1水平及肾脏apoA1表达情况。结果与正常饮食和单独CCl 4注射对照组相比,NASH小鼠出现血肌酐升高,肾小管上皮细胞空泡变性,肾小管损伤标志物NAG、Kim-1表达增高,肾小管上皮细胞转分化标志物α-SMA表达增高。肾组织中apoA1表达增高,表达在近端肾小管上皮细胞胞浆,并在刷状缘上浓聚。连续切片免疫组化染色显示apoA1表达部位与NAG表达高度一致。但NASH小鼠血清apoA1水平较对照组无明显差异。结论本研究发现在NASH相关慢性肾脏病中,apoA1在近端肾小管上皮细胞高表达,与发生肾损伤的小管部位一致,而与血清中apoA1水平无关。ApoA1在NASH相关慢性肾损伤中的具体作用机制需要进一步深入研究。Objective To explore the expression and role of apolipoprotein A1(apoA1)in non-alcoholic steatohepatitis(NASH)-related chronic kidney injury(CKD).Methods A NASH model was established by intraperitoneal injection of western high-calorie diet combined with low-dose carbon tetrachloride(CCl_(4)).The normal diet and intraperitoneal injection of CCl 4 alone were used as the controls.The renal function,histopathological changes,serum apoA1 level and expression level of apoA1 in kidney were detected.Results Compared with the normal diet group and the control group treated with CCl_(4) injection alone,NASH mice showed increased serum creatinine,vacuolar degeneration of renal tubular epithelial cells,increased expression of renal tubular injury markers NAG and Kim-1,and increased expression of renal tubular epithelial transdifferentiation markersα-SMA.The expression of apoA1 increased in renal tissue.It was expressed in the cytoplasm of proximal renal tubule epithelial cells,and concentrated on the brush margin.Immunohistochemical staining of continuous slice showed that the expression site of apoA1 was highly consistent with that of NAG.However,there was no significant difference in serum apoA1 level between NASH mice and the control group.Conclusion In NASH-related chronic kidney disease,apoA1 is highly expressed in proximal renal tubular epithelial cells,consistent with the site of renal injury,but not related to serum apoA1 level.The specific mechanism of action of apoA1 in NASH-related chronic kidney injury needs further in-depth research.

关 键 词：非酒精性脂肪性肝病 非酒精性脂肪肝炎 慢性肾脏病 载脂蛋白A1 

分 类 号：R575[医药卫生—消化系统] R692[医药卫生—内科学]