日本血吸虫感染对高脂饮食小鼠肝组织Arg-1和 Fizz-1表达的影响

Effects of Schistosoma japonicum infection on the expression of Arg-1 and Fizz-1 proteins in liver tis-sues of mice with high-fat diet induced obesity

目的：探讨日本血吸虫感染对高脂饮食小鼠巨噬细胞选择性活化和肥胖小鼠肝脏胰岛素抵抗的影响及可能机制。方法36只雄性 C57BL/6J 小鼠，随机分为正常对照组（normal control group，NC 组；n＝12）、高脂饮食组（high-fat diet group，HF 组；n＝12）及高脂饮食复合日本血吸虫感染组（high-fat diet with Schistosoma japonicum infection group，HSj 组；n＝12）。分别在高脂饲养第6周末及12周末时检测空腹血糖（fasting peripheral blood glucose，FBG）、空腹血浆胰岛素（fasting plasma insulin，FINS）水平，并计算胰岛素抵抗指数（insulin resistance index，HOMA-IR）；逆转录-聚合酶链反应（RT-RCR）和免疫组化分别检测肝脏组织 IL-6及选择活化型巨噬细胞的特异性标志物精氨酸酶-1（arginase-1，Arg-1）、发现于炎症区域（found in inflammatory zone-1，Fizz-1）mRNA 和蛋白表达情况。结果感染第6周末及12周末，HF 组 HOMA-IR 均高于 NC 组和 HSj 组（P﹤0.05）；HF 组感染12周末的 HOMA-IR 比感染6周末高（P＞0.05）。感染6周末 HF 组和 HSj 组 IL-6表达明显高于 NC 组（P﹤0.05），12周末 HF 组 IL-6表达明显高于 HSj 组和 NC 组（P﹤0.05）。感染第6周末及12周末，HF 组Arg-1、Fizz-1表达均低于 NC 组（P﹤0.05）；感染第12周末 HSj 组 Arg-1表达最高，HF 组 Arg-1表达最少；感染第6周末及12周末，HSj 组 Fizz-1表达均高于 HF 组和 NC 组（P﹤0.05）。结论血吸虫尾蚴急性感染（6周）小鼠可能会发挥促炎作用，慢性感染（12周）可能是通过改变肝组织巨噬细胞的极性来逆转饮食诱导肥胖小鼠肝脏的胰岛素抵抗。

Objective To investigate the effects of Schistosoma japonicum infection on selective activation of macrophages and insulin resistance in liver tissues of mice with high-fat diet induced obesity and the possible mechanism. Methods Thirty-six male C57BL/ 6J mice were randomly divided into 3 groups in-cluding normal control group（NC group,n=12）,high-fat diet feeding group（HF group,n=12）and high-fat diet feeding with Schistosoma japonicum infection group（HSj group,n=12）. Specimens were collected 6 and 12 weeks after high-fat diet feeding. The levels of fasting blood glucose（FBG）,fasting plasma insulin （FINS）and homeostasis model assessment for insulin resistance index（HOMA-IR）were detected. The ex-pression of interleukin-6（IL-6）,arginase-1（Arg-1）and found in inflammatory zone-1（Fizz-1）at mRNA and protein levels were detected by semi-quantitative reverse transcription polymerase chain reaction（RT-PCR）and immunohistochemistry,respectively. Results The mice from HF group showed higher levels of HOMA-IR than those form NC group and HSj group by the end of 6 and 12 weeks after infection（P﹤0. 05）. The levels of HOMA-IR in mice from HF group were increased by the end of week 12 after infection as com-pared with those at week 6（P〉0. 05）. The levels of IL-6 in mice from both HF group and HSj group were higher than those from NC group by the end of week 6 after infection（P﹤0. 05）. Higher levels of IL-6 were detected in mice from HF group as compared with those from HSj group and NC group by the end of week 12 after infection（P﹤0. 05）. The expression of Arg-1 and Fizz-1 in mice form HF group were lower than those from NC group by the end of 6 and 12 weeks after infection（P﹤0. 05）. Arg-1 was highly expressed in mice form HSj group,followed by those from NC and HF groups 12 weeks after infection. The expression of Fizz-1 in mice from HSj group was the highest among the three groups by the end of week 6 and 12 after infection （P﹤0. 05）. Conclusion The proinflammatory effects on mice with diet induced obesity were induced during acute infection of Schistosoma japonicum cercariae（6 weeks）. The chronic infection of Schistosoma japonicum cercariae（12 weeks）might be helpful in reversing hepatic insulin resistance in mice with diet induced obesity by changing the polarity of macrophages in liver tissues.