衰老对非酒精性脂肪肝的血清学和形态学变化研究

Effects of aging on serological and hepatic morphological changes in rats with non-alcoholic fatty liver disease

目的通过不同月龄SD大鼠非酒精性脂肪性肝病(NAFLD)模型的建立,探讨分析衰老NAFLD大鼠血清学及肝脏形态学变化。方法雄性SD大鼠按月龄随机分为老年模型组、老年对照组、青年模型组和青年对照组,分别给予45%高脂饮食和普通饮食喂养8周。检测血清生化指标和胰岛素指标,光学显微镜下观察肝脏组织学结构改变。结果大鼠体重随龄增长,模型组体重增长率、肝湿重高于相应对照组(均P<0.01)。模型组谷丙转氨酶、三酰甘油、胆固醇、血糖、空腹胰岛素和胰岛素抵抗指数水平高于对照组(均P<0.05),老年模型组三酰甘油和胰岛素增高更为显著(均P<0.05)。HE染色和油红O染色可见模型组肝细胞肿大,充满脂肪空泡;老年模型组以大泡性脂肪变为主,伴有局部坏死灶。结论短期高脂饮食诱导的NAFLD模型大鼠出现明显的高脂血症、高糖和高胰岛素血症,老年模型组大鼠胰岛素抵抗更为显著,胰岛素敏感性严重减低。

Objective To investigate and analyze serological and hepatic morphological changes in aged rats with non-alcoholic fatty liver disease(NAFLD)by establishing NAFLD model with SD rats at different months of age.Methods Male SD rats were randomly divided into four groups according to age:the aged model group(18-months-old),the aged control group(18-months-old),the young model group(2-months-old)and the young control group(2-months-old),with 12 rats in each group.Rats in the model groups and the control groups were fed a 45%high-fat diet and a normal diet,respectively,for eight weeks.Serum biochemical indexes and the insulin index were measured.Hepatic histological changes were evaluated under a light microscope following HE staining and Oil red staining.Results The body and liver weights of the rats increased with age,and the average rate of weight growth and liver wet weight of the model groups were higher than those of their corresponding control groups(P<0.01).Levels of serum alanine aminotransferase(ALT),triglycerides(TG),cholesterol(CHOL),glucose(GLU),fasting insulin(FINS)and homeostatic model assessment of insulin resistance(HOMA-IR)in the aged model group were higher than those in the corresponding control group and of the young model group(P<0.05).Under the light microscope,hepatic cells stained with HE and Oil red showed diffuse swelling and were full of lipid vacuoles in the model groups.In the aged model group,hepatic cells were characterized by macrovesicular steatosis with focal necrosis.Conclusions Clear hyperlipemia,hyperglycemia and hyperinsulinemia can be seen in a NAFLD model induced by short-term high-fat feeding.Insulin resistance and decreased insulin sensitivity are more significant in aged rats with NAFLD.