日本血吸虫感染对C57BL/6J小鼠脂肪肝及胰岛素抵抗的影响  

Effects of Schistosoma japonicum infection on fatty liver and insulin resistance of C57BL /6J mice

作　　者：赵娜[1] 李素梅[1] 王维[2] 李春燕[1] 方星星[1] 孙科[1] 

机构地区：[1]安徽医科大学附属省立医院内分泌科,合肥230001 [2]安徽医科大学寄生虫学教研室,合肥230032

出　　处：《安徽医科大学学报》2014年第11期1525-1530,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省卫生厅医学科研基金(编号:13zc017)

摘　　要：目的观察血吸虫感染对高脂饮食诱导的脂肪肝小鼠肝组织结构与功能、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)及Ym-1 mRNA表达的影响,探讨巨噬细胞选择性活化对肥胖鼠肝脏及胰岛素抵抗的影响及可能机制。方法建立日本血吸虫感染复合高脂饲养C57BL/6J小鼠模型,测定空腹血糖(FBG)、血浆胰岛素水平(FINS),计算胰岛素抵抗指数(HOMA-IR);测定肝匀浆液谷丙转氨酶(ALT)、三酰甘油(TG)及胆固醇(TC)水平;HE染色观察肝组织病理改变,RT-PCR检测肝组织TNF-α、NF-κB及Ym-1转录水平等。结果 1感染后第6周,高脂(HF)组及高脂感染(HSj)组小鼠体重均较对照(NC)组增加>20%,肥胖模型造模成功。结合肝组织病理,脂肪肝造模成功。2感染后第6周及第12周,HSj组小鼠肝细胞脂肪变性及炎性细胞浸润较同期HF组轻,HSj组HOMA-IR较同期HF组下降(P<0.05)。3感染后第6周和第12周时,HF组TNF-αmRNA及NF-κB mRNA表达高于HSj组和NC组(P<0.05);第6周末时,HF组Ym-1 mRNA的表达高于NC组和HSj组(P<0.05),第12周末时HSj组表达强度高于HF组和NC组(P<0.05),且较6周时表达增强(P<0.05)。4 HF组小鼠HOMA-IR与肝组织TNF-αmRNA光密度相对值呈正相关(r=0.680,P=0.018);HSj组小鼠HOMA-IR与肝组织Ym-1mRNA光密度相对值呈负相关(r=-0.724,P=0.015)。结论肥胖鼠脂肪肝组织中炎症因子TNF-α及调控因子NF-κB的表达水平与胰岛素抵抗的形成有一定关系,日本血吸虫感染通过诱导肥胖鼠巨噬细胞选择性活化Ym-1转录水平增高及TNF-α和NF-κB转录水平的降低,改善胰岛素抵抗,为糖尿病防治研究提供新思路。Objective To observe the effects of schistosoma inflection on fatty liver of C57BL/6J mice induced by high-fat diet, in which the following factors are considered： liver tissue structure and function, tumor necrosis fac- tor-α （TNF-α） , nuclear factor-kappa B （NF-κB） and Ym-1. Besides, to explore infunee and possible mechanism of macrophages alternative activation to liver and insulin resistance in obese mice. Methods High-fat-diet with Schistosoma japonicum infected mice were obtained. The levels of fasting blood glucose （ FBG）, fasting plasma in- sulin （FINS） were measured, and insulin insulin resistance index （HOMA-IR） was calculated. Then the contents of liver homogenate alanine aminotransferase （ALT）, triglyceride （TG） and cholesterol （TC） were detected. Fi- nally, the pathological changes of liver were observed by HE staining. At the same time TNF-α, NF-κB and Ym-1 mRNA were detected by RT-PCR. Results ① By the end of 6th week after infection, the weight of HF and HSj group achieved a 20% rise in comparison with the NC group. Combined with the pathological of liver, obesity and fatty liver of mice were obtained. ② Compared with the same period of HF group, hepatic steatosis, inflammatory cell infiltration and HOMA-IR were weaken in HSj group at 6th and 12th week after infection（P 〈0. 05）. ③ The expression of TNF-α and NF-κB mRNA in HF group were higher than HSj group and NC group by the end of 6th and 12th week after infection （P 〈 0. 05）. And the expression of Ym-1 mRNA in HF group was higher than NC group and HSj group by the end of 6th week （ P 〈 0. 05 ）. The expression intensity of HSj group was higher than that of HF and NC group by the end of 12th week （P 〈0. 05）, and higher than before （P 〈0. 05）. ④ A positive and significant correlation was observed between the HOMA-IR and TNF-α mRNA of HF mice （r = 0. 680, P = 0. 018 ）, no relationship with NF-κB mRNA. Meanwhile, negatively relationship was found between HOMA-IR an

关 键 词：血吸虫 巨噬细胞 炎症因子 胰岛素抵抗 

分 类 号：R383.2[医药卫生—医学寄生虫学] R589.2[医药卫生—基础医学]