日本血吸虫感染对小鼠肝脏脂代谢影响机制的初步研究北大核心CSCD

目的探讨日本血吸虫感染对小鼠肝脏肝细胞脂质沉积的影响及作用机制。方法10只Balb/c小鼠随机分为正常组、感染组,每组5只,感染组小鼠经皮肤感染日本血吸虫尾蚴(15±1)条/只,饲养6周。HE染色观察肝脏病理改变,油红O染色观察肝脏脂质沉积,外周血检测肝功能和血脂水平,实时定量PCR检测肝脏脂代谢相关基因表达水平。可溶性虫卵抗原SEA刺激LO2肝细胞系,Nile red染色观察细胞脂质变化情况,实时定量PCR检测LO2细胞脂质合成相关基因表达水平。结果与正常组比,小鼠感染日本血吸虫后,肝脏出现明显的虫卵肉芽肿和纤维化,外周血中的ALT、AST含量显著升高(t_(ALT)=6.432,P<0.01;t_(AST)=3.259,P<0.05)。感染后肝脏中脂滴明显减少;外周血TG、CHOL的水平显著降低(t_(TG)=7.154,P<0.01;t_(CHOL)=8.749,P<0.001);肝脏中脂质合成相关基因Acly、Accs、Fasn表达水平明显降低(t_(Acly)=3.765,P<0.05;t_(Accs)=2.859,P<0.05;t_(Fasn)=3.888,P<0.05),脂质转运相关基因CD36以及脂质氧化分解相关基因Cpt 1表达水平明显升高(t_(CD36)=8.250,P<0.01;t_(Cpt1)=1.297,P<0.05);细胞水平结果显示,SEA组与DMEM组比,SEA刺激后LO2细胞脂质含量明显减少,脂质合成相关基因SREBP-1C、ACLY、ACC、FASN以及甘油三酯合成相关基因DGAT和GPAT的表达水平显著降低(均P<0.05)。结论日本血吸虫感染通过抑制肝细胞脂质合成和促进脂质分解下调肝脏脂质沉积水平。

Preliminary study of the mechanism of the effects of Schistosoma japonicum infection on liver lipid metabolism in mice

This study aimed to investigate the effects and underlying mechanism of Schistosoma japonicum infection on lipid deposition in hepatocytes. Ten mice were randomly divided into a normal group and infected group (n=5). The mice were infected with 15±1 cercariae through the skin. At 6 weeks after infection, liver pathological changes were observed according to HE staining; lipid deposition in liver was observed according to oil red O staining; liver function and lipid levels were detected; and expression of genes associated with lipid metabolism in the liver was detected with real-time quantitative PCR. The liver cell line LO2 was stimulated by the soluble egg antigen SEA. In these cells, lipid deposition was observed through Nile Red staining, and the expression levels of lipid synthesis associated genes were detected by real-time quantitative PCR. In infected mice, the liver showed severe inflammatory granuloma and fibrosis. ALT and AST in the serum increased significantly after infection (t_ALT=6.432,P<0.01;t_AST=3.259,P<0.05). Interestingly, lipid droplets in the liver significantly decreased after infection, and the levels of TG and CHOL also significantly decreased (t_TG=7.154,P<0.01;t_CHOL=8.749,P<0.001). Compared with those in the normal group, the expression levels of the lipid synthesis related genes Acly, Accs and Fasn were significantly downregulated after infection (t_Acly=3.765,P<0.05; t_Accs=2.859,P<0.05; t_Fasn=3.888,P<0.05), whereas the expression levels of the lipid transport related gene CD36 and the lipid catabolism related gene Cpt 1 were upregulated significantly (t_CD36=8.250,P<0.01; t_Cpt1=1.297,P<0.05, respectively). In vitro, as compared with that in the DMEM group, the lipid content of LO2 cells clearly decreased after SEA stimulation, and the expression levels of the lipid synthesis associated genes SREBP-1c, ACLY, ACC and FASN, and the triglyceride synthesis associated genes DGAT and GPAT, all decreased (P<0.05). S. japonicum infection therefore down-regulates lipid deposition in the liver by inhibiting lipid synthesis and promoting lipid lipolysis in hepatocytes.