Foxp3+Tregs在慢性间歇低氧所致肝损伤中的作用

The role of Foxp3^+T cells in chronic intermittent hypoxia induced liver injury

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。

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.