肾交感神经离断对高脂诱导胰岛素抵抗SD大鼠糖代谢的影响

发布时间：2019-02-18 18:52

【摘要】：目的：探讨肾交感神经离断(RD)对高脂诱导胰岛素抵抗(IR)大鼠葡萄糖代谢动力学和胰岛素信号通路的影响。方法：雄性健康SD大鼠50只,8周龄,随机分为1)普食组(NCD组,n=10)；2)高脂组(HFD组,n=40)；高脂组分为：单侧假手术组(Left SO组,n=10)；单侧手术组(Left RD组,n=10)；双侧假手术组(Bilateral SO组,n=10)；双侧手术组(Bilateral RD组,n=10),均喂养10周。开展肾交感神经离断术,以3-3H-葡萄糖和14C-乳酸为示踪剂,联合高胰岛素-正葡萄糖钳夹技术,综合评价各组大鼠的糖代谢代谢动力学变化。利用Western blot方法检测胰岛素信号通路相关蛋白的活性水平。结果：与普食组(NCD组)相比,高脂组(HFD组)的体重、FFA、 FIns、TG、TC和LDL-C都显著增加。与假手术组相比较,交感神经离断术组的血压及肝糖产生显著下降；而与单侧假手术组及双侧假手术组分别相比,单侧手术组及双侧手术组大鼠肝糖原分解和糖异生能力均显著降低：同时糖异生关键酶G6Pase和PEPCK的表达也下降,而胰岛素作用信号通路关键分子胰岛素受体、胰岛素受体底物及AKT的磷酸化活性程度均不同程度的升高。结论：肾交感神经离断(RD)可能是通过抑制糖原分解和糖异生来降低G6Pase葡萄糖流量和葡萄糖循环,并且通过激活InsR→IRS-1→Akt信号通路来抑制糖异生和糖原分解,增加了高脂诱导胰岛素抵抗大鼠的胰岛素敏感性并且降低了血压。因此,我们推测,RD能够提高机体的胰岛素敏感性,并且改善高脂饮食喂养诱导的胰岛素抵抗。
[Abstract]:Aim: to investigate the effects of (RD) on glucose metabolism and insulin signaling pathway in hyperlipidemic insulin-resistant (IR) rats. Methods: fifty healthy male SD rats, aged 8 weeks, were randomly divided into two groups: 1) normal diet group (NCD group, n = 10), 2) hyperlipidemia group (HFD group, n = 40), 1) unilateral sham operation group (Left SO group, n = 10), 2) hyperlipidemia group (HFD group, n = 40). (Left RD group (n = 10), (Bilateral SO group (n = 10) and (Bilateral RD group (n = 10) were fed for 10 weeks. Using 3-3H-glucose and 14C- lactic acid as tracer, combined with hyperinsulin-positive glucose clamp technique, the dynamic changes of glucose metabolism in rats of each group were comprehensively evaluated. The activity level of insulin signaling pathway related protein was detected by Western blot method. Results: compared with the normal diet group (NCD group), the body weight, FFA, FIns,TG,TC and LDL-C increased significantly in the high fat group (HFD group). Compared with the sham-operated group, the blood pressure and liver sugar were significantly decreased in the sympathetic nerve transection group. Compared with unilateral sham-operation group and bilateral sham-operation group, liver glycogen decomposition and glycometabolism were significantly decreased in unilateral and bilateral operation groups. Meanwhile, the expression of G6Pase and PEPCK, the key enzymes of glycometabolism, was also decreased. The phosphorylation activities of insulin receptor, insulin receptor substrate and AKT were increased in different degrees. Conclusion: (RD) may inhibit G6Pase glucose flow and glucose circulation by inhibiting glycogen decomposition and glycosylated allogeny, and inhibit glycosylation and glycogen decomposition by activating InsR IRS-1 Akt signaling pathway. Increased insulin sensitivity and reduced blood pressure in high-fat-induced insulin-resistant rats. Therefore, we speculate that RD can increase insulin sensitivity and improve insulin resistance induced by high fat diet.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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