三种啮齿类动物非酒精性脂肪肝形成及机制探讨

Formation and mechanism of non-alcoholic fat liver disease in three species of rodents

目的分析物种差异对NAFLD模型复制的影响,探讨不同鼠种NAFLD形成及其机制。方法长爪沙鼠、SD大鼠、ICR小鼠各20只,按种属随机分为对照组及模型组,对照组给予普通饲料,模型组给予高脂饲料。16周后,观察肝脏HE及Mallory三色染色病理变化,计算肝指数,检测血清血脂(CHO、TG、LDL-c、HDL-c)、肝功能(GOP、GPT)及肝组织中抗氧化酶(SOD、GSH-PX、CAT)活性及羟脯氨酸(Hyp)、丙二醛(MDA)、游离脂肪酸(FFA)水平。结果与对照组比较,各模型组:沙鼠Hyp、CHO、TG、LDL-c、HDL-c、肝指数、GOP、GPT、MDA、FFA均升高,SOD、GSH-PX、CAT活性降低(P<0.05,P<0.01),肝脏出现纤维化;大鼠CHO、肝指数、GOP、GPT、FFA、SOD活性升高,MDA含量、GSH-PX、CAT活性降低(P<0.05,P<0.01),有局灶性脂肪肝炎;小鼠CHO、LDL-c、HDL-c、肝指数、CAT活性升高,MDA含量降低(P<0.05,P<0.01),肝脏病理正常。结论三种动物在脂质代谢、肝功能、氧化应激等方面有显著的差异,并形成了不同的NAFLD模型:沙鼠形成伴高TG、CHO血症的肝纤维化模型、大鼠形成伴高CHO血症的局灶性脂肪肝炎模型、小鼠形成高胆固醇血症模型但肝脏未发生明显的病理改变。

Objective To evaluate the formation and mechanism of non-alcoholic fat liver disease （NAFLD） in three species of rodents by analyzing effect of species differences on replication of NAFLD models. Methods Twenty SD rats, 20 ICR mice and 20 Mongolian gerbils were assigned randomly into 2 groups respectively： model group （fed with high fat diet） and control group （fed with normal diet）. After 16 weeks, hepatic pathology was observed with HE and Mallory trichrome staining, and serum lipid levels （CHO, TG, LDL-c, HDL-c） and liver function （GOP, GPT） , liver index, antioxidant enzyme activity （SOD, GSH-PX, CAT）, hydroxyproline, free fatty acid, MDA of liver were detected. Results Compared with the control group, Hyp, CHO, TG, LDL-c, HDL-c, liver index, GOP, GPT, MDA, FFA were significantly increased, whereas SOD, GSH-PX, CAT were significantly decreased in Mongolian gerbils （P 〈0.05, P 〈0.01 ） ; pa- thology showed hepatic fibrosis; CHO, liver index, GOP, GPT, FFA, SOD were significantly increased, whereas MDA, GSH-PX, CAT were significantly decreased in SD rats （P 〈 O. 05, P 〈 0.01 ） , and formed focal non-alcoholic steatohepatitis; CHO, LDL-c, HDL-c, liver index, CAT were significantly increased, whereas MDA was significantly decreased in ICR mice （P 〈 0.05, P 〈 0.01 ） , and the liver histology was normal. Conclusions There are obviously statistical differences in lipid metabolism, liver function and oxidative stress among the three species of rodents. They form different NAFLD models： Mongolian gerbils form liver fibrosis model with high TG, CHO, SD; rats form focal fatty hepatitis with high CHO; and ICR mice form hypercholesterolemia model without pathological changes in the liver.