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
袁玥 1陈琳 1王文姬 1李雪竹1
作者信息
- 1. 上海交通大学医学院附属第九人民医院肾内科,上海 200011
- 折叠
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(CCl4)腹腔注射诱导建立NASH模型,以正常饮食和单独CCl4 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CCl4 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.
Abstract
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(CCl4).The normal diet and intraperitoneal injection of CCl4 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 CCl4 injec-tion alone,NASH mice showed increased serum creatinine,vacuolar degeneration of renal tubular epithelial cells,increased ex-pression of renal tubular injury markers NAG and Kim-1,and increased expression of renal tubular epithelial transdifferentiation markers α-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 ex-pression 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 ex-pressed 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A1Key words
non-alcoholic fatty liver disease/non-alcoholic steatohepatitis/chronic kidney disease/apolipoprotein A1引用本文复制引用
基金项目
国家自然科学基金面上项目(81970622)
出版年
2024
国家科技期刊平台
NSTL
万方数据