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目的:探讨饱和脂肪酸、单不饱和脂肪酸、多不饱和脂肪酸饮食对大鼠肝脏X盒结合蛋白-1(XBP-1)的影响。方法:48只雄性Wistar大鼠随机分为4组:正常对照组(N组)、饱和脂肪酸饮食组(S组)、单不饱和脂肪酸饮食组(M组)、多不饱和脂肪酸饮食组(P组)。正常对照组给基础饲料(脂肪占10.3%);饱和脂肪酸饮食组的饲料是在基础饲料中添加15%猪油;单不饱和脂肪酸饮食组的饲料是在基础饲料中添加15%茶油;多不饱和脂肪酸饮食组的饲料是在基础饲料中添加15%豆油(脂肪占35.4%)。8周后4组各随机选8只大鼠行高胰岛素-正葡萄糖钳夹试验,同时留取空腹状态血清测定血脂、胰岛素等指标。肝脏XBP-1蛋白表达分别用Western blot法和免疫组化法测定。结果:①实验第8周末,与N组相比,P、M、S组大鼠进食量有所减少(P<0.05)。除外进食量的影响,与N组相比,S组血清总胆固醇(TC)、甘油三酯(TG)升高(P<0.05),M、P组差异无统计学意义(P>0.05);S、P组空腹胰岛素(FINS)、空腹血糖(FBG)升高,葡萄糖输注率(GIR)明显下降(P均<0.05),但S、P两组间无统计学意义(P>0.05);M组血清FINS、FBG有升高趋势,差异无统计学意义(P>0.05),GIR明显下降(P<0.05)。与M组相比,S、P组GIR明显下降(P<0.05)。②XBP-1在细胞浆和细胞核均有表达,呈棕黄色或棕褐色染色。N、M组主要在细胞核表达,而P、S组在细胞浆和细胞核均有表达,但是4组间无统计学意义(P>0.05);Western blot显示XBP-1蛋白相对表达的量分别是:M组(0.85±0.15)、N组(0.79±0.14)、P组(1.09±0.16)、S组(1.15±0.21)。与N组比较,P、S组肝脏XBP-1蛋白表达升高,差异有统计学意义(P<0.05);但P、S两组间及N、M两组间比较均无统计学意义(P>0.05)。结论:饱和脂肪酸和多不饱和脂肪酸饮食喂养所致大鼠肝脏中XBP-1蛋白表达明显高于正常对照和单不饱和脂肪酸饮食大鼠组,说明内质网应激可能参与了胰岛素抵抗的发生。
Objective: To investigate the effect of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid diet on hepatic X box binding protein-1 (XBP-1) in rats. Methods: Forty eight male Wistar rats were randomly divided into four groups: normal control group (N group), saturated fatty acid diet group (S group), monounsaturated fatty acid diet group (M group), polyunsaturated fatty acid diet group group). The normal control group fed the basal diet (10.3% fat); the diet of saturated fatty acid diet was fed with 15% lard on the basal diet; the dietary supplementation with monounsaturated fatty acid diet was based on the addition of 15% tea oil to the basal diet Unsaturated fatty acid diet group feed is added to the basic diet of 15% soybean oil (35.4% fat). After 8 weeks, 8 rats in each group were randomly selected for hyperinsulinemic-euglycemic clamp test, and fasting serum samples were taken for determination of serum lipids and insulin. The expression of liver XBP-1 protein was determined by Western blot and immunohistochemistry respectively. Results: At the end of the 8th week, the food intake of rats in P, M and S groups decreased compared with N group (P <0.05). Compared with N group, serum total cholesterol (TC) and triglyceride (TG) in group S increased (P <0.05), but there was no significant difference between group M and group P (P> 0.05). The levels of fasting insulin (FINS), fasting blood glucose (FBG) and glucose infusion rate (GIR) in S and P groups decreased significantly (P <0.05), but there was no significant difference between S and P groups (P> 0.05) The levels of FINS and FBG in M group were higher than those in M group (P> 0.05), and the GIR was significantly decreased (P <0.05). Compared with M group, GIR in S and P group decreased significantly (P <0.05). ② XBP-1 in the cytoplasm and nucleus were expressed in brown or tan staining. The N and M groups were mainly expressed in the nucleus, while the P and S groups were expressed in the cytoplasm and nucleus, but there was no significant difference among the four groups (P> 0.05). Western blot showed that the relative amounts of XBP-1 protein were : M group (0.85 ± 0.15), N group (0.79 ± 0.14), P group (1.09 ± 0.16), S group (1.15 ± 0.21). Compared with N group, the expression of XBP-1 protein in liver increased in P and S groups (P <0.05), but there was no significant difference between P and S groups and between N and M groups P> 0.05). Conclusion: The expression of XBP-1 protein in liver of rats fed with saturated fatty acid and polyunsaturated fatty acid diet was significantly higher than that of normal control group and monounsaturated fatty acid diet group, indicating that endoplasmic reticulum stress may be involved in the occurrence of insulin resistance .