ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica
ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica
复制标题
ApoE 缺陷通过加重小鼠日本血吸虫病中 Th17/Treg 失衡促进肝脏病理学
DOI：
10.1111/pim.12785
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发表时间：
2020-09-03
影响因子：
2.2
通讯作者：
Lei, Jiahui
中科院分区：
文献类型：
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作者：
Guan, Fei;Zhang, Chongyang;Lei, Jiahui
目的用日本血吸虫(S)感染载脂蛋白E基因缺陷(ApoE(-/-))小鼠观察载脂蛋白E对小鼠肝脏免疫病理的影响。方法观察小鼠的活动、食欲、体重、肝重/体重比(HMI)。以虫载量和肝蛋载量作为感染强度。观察肝脏虫卵肉芽肿个数、大小及血清丙氨酸氨基转移酶(ALT)水平。用组织纤维化标志物分析肝纤维化程度，用流式细胞仪检测肝组织Th17和Treg的表达，用定量聚合酶链式反应(QPCR)检测肝组织中rOR-γt、Foxp3、IL-17A和转化生长因子-β1的表达。用血清胆固醇(TC)、甘油三酯(TG)水平和肝脏油红O染色测定脂质代谢。结果在感染ApoE(-/-)的小鼠中，感染强度的增加加重了肝脏的免疫病理(表现为HMI增加、虫卵肉芽肿增加和ALT水平升高)和纤维化(肝脏胶原沉积增加)。APOE缺乏导致肝脏Th17/Treg比值显著升高，血清TC、TG水平升高，肝脏油红O染色增强。结论ApoE缺乏可能通过加重Th17/Treg失衡，改变脂代谢，促进日本血吸虫病小鼠肝脏病理和纤维化的发生。
Aims TheSchistosoma japonicum (S japonicum)-infectedApoEgene deficiency (ApoE(-/-)) mice were used to determine effect of ApoE on hepatic immunopathology. Methods Murine activities and appetite, body weight, and ratio of liver weight to its body weight (Hepatic mass index, HMI) were observed. Worm load and liver egg burden were evaluated as the infection intensity. Number and size of liver egg granulomas and serum levels of alanine aminotransferase (ALT) were investigated. We analysed hepatic fibrosis by markers of fibrosis in tissue, detected hepatic Th17 and Treg frequency by flow cytometry, and measured hepatic expressions of ROR gamma t, Foxp3, IL-17A and TGF-beta 1 via qPCR. Lipid metabolism was determined by serum levels of cholesterol (TC) and triglyceride (TG) as well as hepatic Oil red O staining. Results In the infectedApoE(-/-)mice, the increased infection intensity aggravated the hepatic immunopathology (evidenced by increased HMI, elevated egg granulomas and increased ALT levels) and fibrosis (increased hepatic collagen deposition). ApoE deficiency resulted in significantly elevated ratio of hepatic Th17/Treg and higher serum levels of TC and TG, along with higher level of hepatic Oil red O staining. Conclusions ApoE deficiency promotes hepatic pathology and fibrosis by exacerbating Th17/Treg imbalance and altering lipid metabolism in murine schistosomiasis japonica.