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胃饥饿素/肽YY/刺鼠相关蛋白信号在胃旁路手术治疗2型糖尿病中的作用

The roles of ghrelin/agouti-related protein/peptide YY signal pathway in gastric bypass operation for type 2 diabetes

摘要目的 探讨胃饥饿素(Ghrelin)、肽YY(PYY)、刺鼠相关蛋白(AGRP)信号通路在胃旁路手术治疗2型糖尿病中的作用及其机制.方法 采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分为糖尿病非手术对照组(NO组,n=10)和糖尿病Roux-en-Y胃旁路术(RYGB)组(RYGB组,n=10),另外再选10只正常大鼠作为对照组(NC组),对手术组实施胃旁路手术,分别于术前、术后检测各组大鼠血糖(GLU)、总胆固醇(TCH)及三酰甘油(TG)、Ghrelin水平,每天定时监测大鼠饮水量、饮食量以及体重的变化,术后第4周取大鼠下丘脑,检测下丘脑中PYY、AGRP mRNA的表达水平.结果 术后第4周,RYGB组大鼠血糖下降至(6.18 ±0.77) mmol/L、血脂下降至(2.45±0.23) mmol/L;TCH下降至(2.07 ±0.22) mmol/L,进食、水量已接近正常水平,Ghrelin下降至(410.60 ±58.33) ng/L、AGRPmRNA下降至0.80±0.13,较NO组明显降低,而PYYmRNA升高至1.60±0.25,较NO组明显升高(P<0.05).结论 胃旁路手术可以改善2型糖尿病的GLU水平,Ghrelin可能通过PYY、AGRP信号调节2型糖尿病的能量代谢平衡,提示Ghrelin与下丘脑PYY、AGRP调节通路可能对胃旁路手术后2型糖尿病病情缓解起重要作用.

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abstractsObjective To study the roles of ghrelin,agouti-related protein (AGRP) and peptide YY (PYY) signal in treatment of type 2 diabetes mellitus by gastric bypass operation.Methods Twenty adult SD rats were used to establish the model of type 2 diabetes mellitus,and divided into 2 groups:No operation group (NO,n =10) and Roux-en-Y gastric bypass operation group (RYGB,n =10),and another ten adult rats were used as the Normal Control group (NC,n =10).The RYGB group were performed operation after the rat model of type 2 diabetes mellitus were established successfully.The blood were separately collected to examine ghrelin,blood sugar,cholesterol and triglyceride before and after operation,and we monitored the consumption of food and water everyday.The hypothalamus tissues were collected at the 4th week after operation to examine the expression of AGRP and PYY mRNA.Results At the 4th week after operation,the blood sugar dropped to (6.18 ±0.77) mmol/L,Triglycerides dropped to (2.45 ±0.23) mmol/L;Cholesterol dropped to (2.07 ± 0.22) mmoL/L and the consumption of food,water of RYGB group were nearly down to normal level.The level of ghrelin dropped to (410.60 ± 58.33) ng/L,AGRP mRNA dropped to 0.80 ±0.13 in hypothalamus were lower than NO group after operation,the level of PYY mRNA rised to 1.60 ± 0.25 were significantly increased (P < 0.05).Conclusion We can conclude that the situation of type 2 diabetes mellitus can be controlled by Roux-en-Y gastric bypass operation.Ghrelin may regulate the energy metabolism of type 2 diabetes mellitus via AGRP and PYY signals.Our results suggest that the roles of ghrelin,AGRP and PYY signals may play an important role in the control of type 2 diabetes mellitus after Roux-en-Y gastric bypass operation.

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