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中华肥胖与代谢病电子杂志

中华肥胖与代谢病电子杂志 ›› 2017, Vol. 03 ›› Issue (04) : 198 -207. doi: 10.3877/cma.j.issn.2095-9605.2017.04.005

所属专题： 文献；

专题论著

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
卢存龙1, 李宇1, 李龙1, 石拓1, 朱厚鑫1, 周岩冰1,†()   
  1. 1. 266000　青岛，青岛大学附属医院胃肠外科
  • 收稿日期:2017-10-22 出版日期:2017-11-30
  • 通信作者: 周岩冰
  • 基金资助:
    山东省自然科学基金资助项目(ZR2012HM046)

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

Cunlong Lu1, Yu Li1, Long Li1, Tuo Shi1, Houxin Zhu1, Yanbing Zhou1,†()   

  1. 1. Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Shandong 266000, China
  • Received:2017-10-22 Published:2017-11-30
  • Corresponding author: Yanbing Zhou
  • About author:
    Corresponding author: Zhou Yanbing, Email:
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引用本文：

卢存龙, 李宇, 李龙, 石拓, 朱厚鑫, 周岩冰. 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[J]. 中华肥胖与代谢病电子杂志, 2017, 03(04): 198-207.

Cunlong Lu, Yu Li, Long Li, Tuo Shi, Houxin Zhu, Yanbing Zhou. Effects and mechanisms of Roux-en-Y gastric bypass and sleeve gastrectomy on metabolism in hyperuricemic rat model[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2017, 03(04): 198-207.

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。

关键词: Roux-en-Y胃旁路手术, 袖状胃切除术, 高尿酸血症大鼠模型, 尿酸, 糖脂代谢
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-α and 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 and 2, 4, 6, 8 weeks following surgical operations. Pre- and 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-α level 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-α in 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(HOMA-IR score), serum triglyceride and total cholesterol levels were significantly decreased (P<0.01). RYGB and SG surgery lowered serum LPS, IL-6, TNF-α and 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.

Key words: Roux-en-Y gastric bypass surgery, Sleeve gastrectomy, Hyperuricemic rat mdoel, Uric acid, Glycolipid metabolism
表1 RYGB和 SG术后各组大鼠体重的变化（±s, g）
组别 例数 术前 术后2周 术后4周 术后6周 术后8周
Control 10 331.6±8.70 358.2±9.38 385.7±15.54 419.0±15.68 454.8±12.44
Sham 10 332.4±13.57 347.0±7.85 355.2±8.93 391.0±10.70 431.2±9.84
RYGB 8 341.5±13.63 319.5±10.60c 300.4±8.87c 308.7±9.31c 331.0±10.60c
SG 10 336.8±14.90 316.0±10.0c 297.0±11.24c 319.7±6.75c 355.0±6.85c,e
表2 RYGB和SG术后各组大鼠食物摄入量的变化（±s, g/week）
组别 例数 术前 术后2周 术后4周 术后6周 术后8周
Control 10 25.06±0.69 25.44±0.89 25.18±0.77 25.54±0.63 25.41±0.76
Sham 10 25.74±0.65 24.52±1.40 25.24±1.08 25.36±1.23 25.31±0.95
RYGB 8 25.45±0.78 22.80±0.65c 22.48±0.43c 22.26±0.79c,e 22.40±0.60c,e
SG 10 25.21±0.84 22.64±1.13c 22.71±0.63c 23.40±0.49c 23.53±0.46c
图1 RYGB和 SG 术后各组大鼠体重的变化
图2 RYGB和 SG 术后各组大鼠食物摄入量的变化
表3 RYGB和 SG术后各组大鼠血清生化指标的变化（±s）
? Control Sham
? 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10) 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10)
SUA (umol/L) 145.6±6.37 141.9±8.51 149.35±6.12 149.55±5.98 150.1±7.0 199.5±12.8a 196.5±11.6 182.74±10.67 179.31±10.9 175.46±13.3
BUN (mmol/L) 6.19±0.67 6.92±1.26 6.31±0.54 6.76±0.65 6.65±0.78 13.68±1.47a 13.92±1.08 13.35±1.80 12.03±1.60 10.75±1.88
CR (umol/L) 64.81±8.52 67.7±9.51 69.33±5.83 70.48±5.48 70.58±5.32 109.65±10.6a 109.51±14.6 101.32±13.86 96.20±13.27 87.27±10.87
FPG (mmol/L) 5.15±0.74 5.14±0.77 5.62±0.31 5.56±0.51 5.53±0.61 7.17±0.64a 7.40±0.70 7.36±0.67 7.12±0.60 7.16±0.81
FINS (mIU/L) 10.38±0.62 10.48±0.56 10.41±0.63 10.03±0.42 10.28±0.54 14.18±0.65a 13.84±0.62 13.32±0.45 12.80±0.30 12.43±0.44
HOMA-IR 1.52±0.11 1.53±0.096 1.56±0.103 1.47±0.096 1.50±0.076 2.23±0.16a 2.21±0.173 2.12±0.109 2.07±0.090 2.02±0.148
TG (mmol/L) 0.89±0.16 1.03±0.17 1.09±0.17 1.10±0.22 1.19±0.24 1.67±0.11a 1.64±0.25 1.73±0.198 1.87±0.23 1.87±0.23
TC (mmol/L) 1.57±0.26 1.60±0.29 1.61±0.16 1.60±0.21 1.71±0.18 2.34±0.27a 2.35±0.28 2.41±0.36 2.50±0.29 2.65±0.15
? RYGB SG
? 0 W(n=10) 2 W(n=8) 4 W(n=8) 6 W(n=8) 8 W(n=8) 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10)
SUA (umol/L) 195.1±11.6a 187.05±10.23 178.15±10.70 168.5±6.36c 159.33±8.54c 195.0±16.7a 187.1±14.16 176.65±11.58 166.4±8.30c 157.74±6.16c
BUN (mmol/L) 13.81±1.45a 12.81±1.06 11.17±1.11b 10.14±1.00b 8.73±0.92c 13.35±0.88a 12.64±1.71b 10.74±2.87c 9.14±2.50d 8.33±1.78c
CR (umol/L) 106.0±11.72a 97.95±12.69 87.03±10.01c 77.91±9.77c 70.92±7.06c 111.9±14.20a 102.67±12.4 93.31±7.68c 81.51±7.28c 76.98±7.41c
FPG (mmol/L) 7.14±1.11a 6.78±0.85 6.36±0.75b 6.10±0.67c 6.09±0.63c 7.46±0.65a 6.90±0.50 6.43±0.63b 6.23±0.70c 6.21±0.51c
FINS (mIU/L) 14.18±0.53a 13.06±0.55c 12.39±0.32c 11.65±0.28c 11.07±0.36c 14.04±0.46a 13.30±0.51 12.54±0.51c 11.70±0.56c 11.51±0.73c
HOMA-IR 2.33±0.16a 1.94±0.400b 1.93±0.107d 1.76±0.059d 1.64±0.073d 2.30±0.06a 2.07±0.09 1.93±0.083d 1.77±0.096d 1.65±0.076d
TG (mmol/L) 1.72±0.09a 1.61±0.11 1.46±0.116c 1.23±0.08c 1.15±0.10d 1.72±0.17a 1.62±0.18 1.47±0.125c 1.32±0.10c 1.46±0.17c,e
TC (mmol/L) 2.41±0.30a 2.33±0.19 2.21±0.32 2.05±0.30c 1.90±0.12d 2.43±0.21a 2.34±0.24 2.05±0.332b 2.00±0.40d 1.98±0.16d
图3 RYGB和SG对高尿酸血症大鼠血清尿酸、尿素氮和肌酐水平的影响
图4 RYGB和SG对高尿酸血症大鼠空腹血糖、胰岛素和HOMA-IR的影响
图5 RYGB和SG对高尿酸血症大鼠血清甘油三酯和总胆固醇水平的影响
表4 RYGB和 SG 对血清LPS、IL-6、TNF-α炎症指标和黄嘌呤氧化酶XO的影响（±s）
? Control Sham
? 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10) 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10)
LPS(EU/L) 0.26±0.05 0.27±0.05 0.30±0.04 0.28±0.05 0.31±0.05 0.63±0.04a 0.62±0.03 0.61±0.05 0.60±0.06 0.61±0.04
IL-6(ng/L) 10.02±0.63 10.13±0.30 10.63±0.50 11.06±0.54 10.29±0.68 17.80±1.00a 17.33±0.96 16.85±0.95 16.59±1.16 16.10±0.82
TNF-α(ng/dl) 24.42±1.16 24.32±1.12 24.37±0.70 24.45±1.03 24.78±0.71 36.98±0.92a 36.36±0.77 35.71±0.85 35.19±0.92 34.82±0.72
XO(U/L) 8.61±0.43 8.42±0.47 8.40±0.57 8.52±0.36 8.94±0.52 13.70±0.57a 13.11±0.46 12.80±0.31 12.56±0.28 12.03±0.38
? RYGB SG
? 0 W(n=10) 2 W(n=8) 4 W(n=8) 6 W(n=8) 8 W(n=8) 0 W(n=10) 2 W(n=10) 4 W(n=10) 6 W(n=10) 8 W(n=10)
LPS(EU/L) 0.61±0.06a 0.57±0.07 0.53±0.03c,e 0.52±0.04c,f 0.50±0.02c,f 0.63±0.07a 0.63±0.07 0.62±0.07 0.58±0.04 0.57±0.04b
IL-6(ng/L) 17.90±0.92a 16.39±0.61b,e 15.37±0.42b,f 14.37±0.62c 12.63±0.73c 17.93±0.94a 17.27±0.73 16.50±0.39 15.77±0.42b 14.83±0.43c
TNF-α(ng/dl) 36.47±0.81a 35.21±0.81c 33.47±0.88c 31.77±0.77c 29.68±0.97c 36.83±0.91a 35.44±0.43b 34.21±0.58c 34.91±0.73c 31.18±0.81c
XO(U/L) 13.94±0.36a 12.55±0.60b 11.69±0.30c 10.84±0.45c 9.98±0.47c 13.83±0.54a 12.93±0.52 11.70±0.30c 11.74±0.38c 10.52±0.63c
图6 RYGB和SG对高尿酸血症大鼠血清LPS、XO、IL-6和TNF-α的影响
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