中枢输注Sfrp5对高脂饮食诱导的胰岛素抵抗大鼠的糖代谢的影响

发布时间：2018-06-12 07:01

本文选题：分泌性卷曲蛋白5 + 肝糖代谢　；参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:探究中枢输注Sfrp5对高脂饮食诱导的胰岛素抵抗大鼠的糖代谢的影响及相关机制研究。方法:选取健康雄性SD大鼠进行随机分组,分组情况如下:1)普食+第三脑室注射人工脑脊液组(NCD+icv a CSF,n=6),2)普食+第三脑室注射Sfrp5组(NCD+icv Sfrp5,n=6),3)高脂+第三脑室注射人工脑脊液组(HFD+icv a CSF,n=6),4)高脂+第三脑室注射Sfrp5组(HFD+icv Sfrp5,n=6),5)普食+第三脑室输注人工脑脊液+生理盐水静脉输注组(NCD+icv a CSF+iv Saline,n=6),6)普食+第三脑室输注人工脑脊液+脂肪乳剂静脉输注组(NCD+icv a CSF+iv.Lipid,n=6),7)普食+第三脑室输注Sfrp5+生理盐水静脉输注组(NCD+icv Sfrp5+iv Saline,n=6),8)普食+第三脑室输注Sfrp5+脂肪乳剂静脉输注组(NCD+icv Sfrp5+iv.Lipid,n=6),9)高脂+第三脑室输注人工脑脊液+迷走神经复合体输注生理盐水组(HFD+icv a CSF+DVC saline,n=6),10)高脂+第三脑室输注人工脑脊液+迷走神经复合体MK801组(HFD+icv a CSF+DVC MK801,n=6),11)高脂+第三脑室输注Sfrp5+迷走神经复合体生理盐水组(HFD+icv Sfrp5+DVC saline,n=6),12)高脂+第三脑室输注Sfrp+迷走神经复合体MK801组(HFD+icv Sfrp5+DVC MK801,n=6),13)高脂+第三脑室输注人工脑脊液组(HFD+icv a CSF,n=6),14)高脂+第三脑室输注格列苯脲组(HFD+icv Glibenclamide,n=6),15)高脂+第三脑室输注Sfrp5组(HFD+icv Sfrp5,n=6),16)高脂+第三脑室输注格列苯脲/Sfrp5组(HFD+icv Glibenclamide/Sfrp5,n=6),17)高脂+第三脑室输注二氮嗪组(HFD+icv Diazoxide,n=6)。实验大鼠通过高脂饮食诱导其胰岛素抵抗,通过第三脑室微量给药系统的构建、第四脑室孤束核微量给药系统构建,利用扩展高胰岛素正糖钳夹技术评估各组大鼠的肝脏的糖代谢及胰岛素敏感性的变化。结果:高脂大鼠的摄食、体重、肛温较普食大鼠显著升高(P0.01),而氧气的消耗量(VO2)、二氧化碳的消耗量(VCO2)及呼吸商(RER)均显著降低(P0.01);中枢SFRP5表达增高后,即HFD+icv Sfrp5组较HFD+icv a CSF组,摄食、体重、肛温均明显降低(P0.05或P0.01),氧气的消耗量(V02)、二氧化碳的生成量(VCO2)及呼吸商(RER)均显著升高(P0.01);腹腔注射葡萄糖耐量试验(IPGTT)中,HFD+icv Sfrp5组大鼠的血糖及血胰岛素曲线下面积较HFD+icv a CSF组显著减少(P0.01);大鼠行脂质灌注及高胰岛素正糖钳夹技术达钳夹稳态时,中枢Sfrp5表达增高(即NCD+icv Sfrp5+iv.Lipid组)与第三脑室输注人工脑脊液(即NCD+a CSF+iv.Lipid组)相比葡萄糖输注率(GIR)、葡萄糖清除率(GRd)及肝糖生成抑制率均显著升高、肝糖生成率(HGP)显著降低(P0.01);第四脑室孤束核输注MK801可以阻断中枢Sfrp5表达增高对高脂饮食诱导的胰岛素抵抗大鼠肝糖代谢紊乱的改善作用,然而单独仅从第四脑室孤束核输注MK801对高脂饮食诱导的胰岛素抵抗大鼠的肝糖代谢无影响;高脂饮食诱导胰岛素抵抗大鼠行高胰岛素正糖钳夹技术达钳夹稳态时,第三脑室输注Sfrp5蛋白与第三脑室输注人工脑脊液组相较,其葡萄糖输注率、葡萄糖清除率及肝糖抑制率均显著升高、肝糖生成率显著降低(P0.01),而第三脑室Sfrp5联合输注格列苯脲可阻断这一效;另外,第三脑室单独输注格列苯脲无法改善胰岛素抵抗大鼠的糖代谢;同时,第三脑室输注二氮嗪(即HFD+icv Diazoxide组)较第三脑室输注人工脑脊液组(即HFD+icv a CSF组)相比,GIR、GRd及肝糖生成抑制率均显著升高、HGP显著降低(P0.01)。结论:中枢Sfrp5表达增高可以改善高脂饮食诱导的胰岛素抵抗大鼠的胰岛素抵抗情况及糖代谢紊乱,其机制可能是“脑肝轴”及依赖下丘脑的ATP敏感钾离子通道。
[Abstract]:Objective: To investigate the effect of central infusion of Sfrp5 on glucose metabolism in rats with high fat diet induced insulin resistance. Methods: healthy male SD rats were randomly divided into groups as follows: 1) universal diet + third ventricle injection of artificial cerebrospinal fluid (NCD+icv a CSF, n=6), 2) Sfrp5 group (NCD+icv S) + third ventricle injection (NCD+icv S) Frp5, n=6), 3) high fat + third ventricle injection of artificial cerebrospinal fluid group (HFD+icv a CSF, n=6), 4) high fat + third ventricle injection Sfrp5 group (HFD+icv Sfrp5, n=6), 5) common food + third ventricle infusion of artificial cerebrospinal fluid + physiological saline intravenous infusion group (NCD+icv a), 6) intravenous infusion of artificial cerebrospinal fluid + fat emulsion infusion with third ventricle infusion Group (NCD+icv a CSF+iv.Lipid, n=6), 7) universal food + third ventricle infusion Sfrp5+ physiological saline intravenous infusion group (NCD+icv Sfrp5+iv Saline, n=6), 8) common food + third ventricle infusion of Sfrp5+ fat emulsion infusion group (NCD+icv Sfrp5+iv.Lipid, 9), 9) high fat + third ventricle infusion of artificial cerebrospinal fluid + vagus complex infusion of saline group. D+icv a CSF+DVC saline, n=6), 10) high fat + third ventricle infusion of artificial cerebrospinal fluid + vagus complex MK801 group (HFD+icv a CSF+DVC MK801, n=6), 11) high fat + third ventricle infusion of Sfrp5+ vagus complex physiological saline group, 12) high fat + third ventricle infusion of vagus complex complex ICV Sfrp5+DVC MK801, n=6), 13) high fat + third ventricle infusion group (HFD+icv a CSF, n=6), 14) high fat + third ventricle infusion of glibenclamide group (HFD+icv Glibenclamide, n=6), 15) high fat + third ventricle infusion (16), 16) high fat + third ventricle infusion of glibenclamide group (17) 17) high fat + third ventricle infusion (HFD+icv Diazoxide, n=6). The experimental rats induced their insulin resistance by high fat diet, construction of the micro administration system in the third ventricle and the construction of the micronucleus system in the fourth ventricle of the nucleus tractus soliton, and used the extended hyperinsulinemic clamp technique to evaluate the glucose metabolism of the liver in each group. Changes in insulin sensitivity. Results: the feeding, weight, and Anal temperature of high fat rats were significantly higher than that of the general diet rats (P0.01), while oxygen consumption (VO2), carbon dioxide consumption (VCO2) and respiratory quotient (RER) were significantly decreased (P0.01), and when the expression of central SFRP5 was increased, the HFD+icv Sfrp5 group was more than HFD+icv a CSF group, and the feeding, weight, and Anal temperature were both obvious. Reducing (P0.05 or P0.01), oxygen consumption (V02), carbon dioxide production (VCO2) and respiratory quotient (RER) were significantly increased (P0.01); in the peritoneal injection of glucose tolerance test (IPGTT), the area of blood glucose and blood insulin in HFD+icv Sfrp5 rats was significantly lower than that in HFD+icv a CSF group; rats were treated with lipid perfusion and hyperinsulinemia. When the clamp technique reached homeostasis, the increased Sfrp5 expression (NCD+icv Sfrp5+iv.Lipid group) was compared with the glucose infusion rate (GIR) compared with the third ventricle infusion (NCD+a CSF+iv.Lipid group), the glucose clearance rate (GRd) and the inhibition rate of liver sugar production were significantly increased, the liver sugar production rate (HGP) decreased significantly (P0.01), and the fourth ventricle isolated (P0.01). Nucleus infusion of MK801 can block the improvement of central Sfrp5 expression in the hyperlipidemic insulin resistant rat liver glucose metabolism disorder. However, only the infusion of MK801 alone from the nucleus of the solitary tract of the fourth ventricle has no effect on the liver glucose metabolism in the insulin resistant rats induced by high fat diet; high fat diet induces insulin resistance rats to conduct high pancreas. When the isosin positive sugar clamp technique reached the clamp steady state, the glucose infusion rate, the glucose clearance rate and the liver sugar inhibition rate were significantly higher in the third ventricle infusion Sfrp5 protein than in the third ventricle injection artificial cerebrospinal fluid group, and the liver sugar production rate decreased significantly (P0.01), while the third ventricle Sfrp5 combined infusion of glibenclamide could block this effect; in addition, A single infusion of glibenclamide in the third ventricle could not improve glucose metabolism in insulin resistant rats; at the same time, compared with the third ventricle infusion of artificial cerebrospinal fluid (HFD+icv a CSF group), the inhibition rates of GIR, GRd and liver sugar were significantly increased and HGP significantly decreased (P0.01). Conclusion: the central Sfrp5 table was found in the third ventricle infusion two azinazine (group HFD+icv Diazoxide). Hyperlipidemia can improve insulin resistance and glucose metabolism disorder in rats induced by high fat diet. The mechanism may be the "brain liver axis" and the ATP sensitive potassium channel that depends on the hypothalamus.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1

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