Foxp3+Tregs在慢性间歇低氧所致肝损伤中的作用

摘要

Objective To explore the role of Foxp3+ T cells (Tregs) in liver injury induced by chronic intermittent hypoxia. Methods Thirty-two male Wister rats were divided into four groups:control group (A), high-fat diet group (B), intermittent hypoxia group (C), and high-fat diet and intermittent hypoxia group (D). After 4 weeks, blood samples were collected and livers were surgically removed. Using the standard automatic clinical analyzer to test serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL- C), alanina aminotransferase (ALT) and aspartato aminotransferase (AST). The MDA content of liver tissue was measured by colorimetrc method. The levels of TNF-αand IL-1βwere measured by radiommunoassay, and the expression of Foxp3 protein was measured by Western blotting technique. Results Serum levels of TC and LDL-C were significantly higher in B group than those of A, C and D groups, and which were higher in D group than those of A and C groups (P<0.05). There were no significant differences in serum levels of TC and LDL-C between A group and C group. Serum levels of ALT, AST, MDA, TNF-αand IL-1βwere significantly higher in C group than those of A group, and which were significantly higher in D group than those of A, B and C groups (P<0.05). There were no significant differences in these indicators between A group and B group, and between B group and C group. Foxp3 protein expression in liver was significantly lower in D group than that of other groups (P<0.05). Conclusion Foxp3+T regulatory cells involve in the regulation of hepatic injury induced by chronic intermittent hypoxia on the basis of a high-fat diet, and which may play an important role in this process of protective immune response.%目的：探讨叉头样转录因子P3（Foxp3）阳性调节性T细胞（Tregs）在慢性间歇低氧诱导的肝损伤中的作用。方法32只雄性Wistar大鼠随机均分为空白对照组（A组）、高脂饮食组（B组）、间歇低氧组（C组）和高脂饮食+间歇低氧组（D组）。实验暴露4周后留取血标本并分离出肝组织，采用全自动分析仪检测各组大鼠血总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）的水平，比色法测定肝组织丙二醛（MDA）含量，放射免疫法检测促炎症细胞因子肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β水平，Western blot法检测肝组织Foxp3蛋白表达。结果各组TC、LDL-C比较均是B组高于A、C、D组，D组高于A、C组（均P＜0.05），而A组与C组差异无统计学意义。ALT、AST、MDA、TNF-α、IL-1β水平比较均是C组高于A组，D组高于A、B、C组（均P＜0.05），而A组与B组、B组与C组间差异均无统计学意义。D组肝组织Foxp3蛋白表达水平明显低于其他各组（P＜0.05）。结论 Foxp3+Tregs参与在高脂饮食基础上慢性间歇低氧所致的肝损伤的调节，在此过程中可能起重要的保护性免疫作用。