Roux-en-Y胃旁路手术和袖状胃切除术对高尿酸血症大鼠代谢的影响及机制研究

Effects and mechanisms of Roux-en-Y gastric bypass and sleeve gastrectomy on metabolism in hyperuricemic rat model

目的探究两种主要的减重手术Roux-en-Y胃旁路手术(RYGB)和袖状胃切除术(SG)对高尿酸血症(HUA)大鼠血尿酸(SUA)、糖代谢、脂代谢的影响,并通过观察术后炎症性指标,包括脂多糖(LPS)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和黄嘌呤氧化酶(XO)水平的变化,来探究其相关的机制。方法 Wistar大鼠随机分为模型组(Model)和对照组(Control),模型组给予含酵母膏的标准饲料饮食和腺嘌呤、氧嗪酸钾灌胃处理建立高尿酸血症大鼠模型,对照组自由进食正常饲料,模型组经上述处理三周后随机分为三个亚组:RYGB组、SG组和假手术组(Sham),随后进行不同手术处理。术前与术后2、4、6、8周分别对大鼠的体重、食物摄入量进行记录。术前与术后对血清尿酸、肌酐(Cr)和尿素氮(BUN)、空腹血糖(FPG),空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、血清甘油三酯(TG)和总胆固醇(TC)等生化指标和LPS、IL-6、TNF-α等炎症指标和XO浓度进行检测。结果术前,与对照组相比,模型组大鼠血尿酸、血尿素氮、肌酐和空腹血糖、血脂等生化指标及LPS、IL-6和TNF-α等炎性指标水平显著增高(P<0.001)。术后RYGB组和SG组较Sham组体重、食物摄入量减少,SUA、BUN和Cr水平,FPG、FINS、HOMA-IR、血清TG和TC水平显著降低(P<0.01)。与Sham组相比,术后RYGB和SG组血清LPS、IL-6、TNF-α水平和XO浓度显著降低(P<0.01)。结论胃旁路手术和袖状胃切除术能够降低高尿酸血症大鼠血尿酸水平,同时改善高尿酸血症导致的血糖、血脂代谢紊乱,其机制可能与减重手术减少体脂量、缓解炎症反应和胰岛素抵抗、调控黄嘌呤氧化酶的表达有关。

Objective To investigate the effects of Roux-en-Y gastric bypass(RYGB)and sleeve gastrectomy(SG)on metabolism of serum uric acid,blood glucose and lipid profiles in hyperuricemic rat model,and by observing the alteration of serum LPS,IL-6,TNF-αand XO to explore the related mechanism.Methods Forty Wistar rats were randomly divided into hyperuricemic model group and control group.The model group were administered high purine food and orally intragastrical adenine and potassium oxonate to establish the hyperuricemic rat model while the control group was fed on standard food.Three weeks later,the model group was assigned to three subgroups:RYGB,SG,Sham.Then different operational procedures were performed.Body weight and amounts of food intake were recorded before the surgery and2,4,6,8weeks following surgical operations.Preand postsurgical serum uric acid,BUN and creatinine,fasting plasm glucose,fasting insulin concentration,HOMA-IR,triglyceride and total cholesterol were assessed.Serum LPS,IL-6,TNF-αlevel and concentration of XO were measured.Results Preoperatively,compared with control group,serum uric acid,urea nitrogen,creatinine level of model group significantly increased,indicating that the established hyperuricemic rat model by high purine food intake and oral intragastrical administration of adenine and potassium oxonate was successful.The biochemical index of fasting blood glucose and lipid profiles and inflammatrory markers LPS,IL-6,TNF-αin model groups was much higher than that in control group(P<0.001).After surgery,compared with Sham group,body weight,amount of food intake,serum uric acid serum urea nitrogen and creatinine levels and fasting plasm glucose,serum insulin,insulin resistance index(HOMAIR score),serum triglyceride and total cholesterol levels were significantly decreased(P<0.01).RYGB and SG surgery lowered serum LPS,IL-6,TNF-αand XO concentration compared with Sham group(P<0.01).Conclusions RYGB and SG surgery significantly reduced serum uric acid level and improved the imbalance of metabolism of glucose and lipid profiles of hyperuricemic rat.Mechanically,RYGB and SG surgery might reduce serum uric acid by reducing fat mass,relieving inflammation and insulin resistance as well as regulating the expression of XO.