动物造模 z-bio 2021-09-15 536

　　Objective: To discuss the effect of high-fat diet on insulin resistance (IR) and the expression of liver insulin receptor substrates (IRS) 1 and 2 in Tibet mini-pigs.

　　Method: 10 Tibetan miniature pigs were randomly divided into normal control group (Ctr), 5 animals were fed with ordinary feed, and IR model (IR model) group, 5 were fed with high-fat feed, and the model was continuously modeled for 12 weeks. Twelve weeks after modeling, weigh and measure body length, calculate body mass index (BMI), take anterior vena cava blood on an empty stomach to determine total cholesterol (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL) -C), triglycerides (TG), free fatty acids (FFA), fasting blood glucose (FBG) and insulin (insulin), calculate the homeostasis model assessment-estimated insulin resistance (HOMA-IR); stop glucose tolerance at the same time Experiment, and calculate the area under the glucose tolerance curve (AUC); take liver tissue to detect IRS-1 and IRS-2 gene and protein expression, and perform oil red O, PAS and HE staining to observe liver lipid accumulation, glycogen and tissue respectively Pathological changes.

　　Results: Compared with the normal control group, the weight, BMI index, TC, LDL-C, HDL-C, FFA, FBG, insulin and HOMA-IR index of the IR model group were significantly increased (P<0.05, P<0.01); The glucose tolerance test showed that the curve of blood glucose and insulin levels was delayed, while AUC blood glucose and AUC insulin were significantly increased (P<0.05, P<0.01); lipid accumulation, increased glycogen, and turbidity of some liver cells appeared in liver tissue. Local nuclei disappeared or were squeezed to one end, occasionally lymphocyte infiltration; at the same time, the expression of IRS-1 and IRS-2 mRNA and protein in liver tissue were significantly reduced (P<0.05, P<0.01).

　　Conclusion: High-fat diet can cause insulin resistance in Tibetan mini-pigs. The decreased expression of IRS-1 and IRS-2 in liver tissue is one of the molecular mechanisms that high-fat diet affects the insulin sensitivity of Tibetan mini-pigs.