四种减重方式对2型糖尿病疗效的随机对照动物实验研究
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摘要
目的:通过随机区组的对照实验,研究胃旁路减肥术(GastricBy-pass)、袖状胃减容术(Sleeve Gastrectomy)、胃束带减肥术(Gastric Lap-Band)和饮食控制(Alimentary Control)这四种减重方法对经链脲佐菌素(STZ)建模的2型糖尿病大鼠的体重控制及血糖控制效果,试图找到新的有效的2型糖尿病(T2DM)治疗方法,并初步探索血糖控制与体重减轻之间的关系并分析其作用机理。
方法:对雄性SD大鼠腹腔沣射STZ建立2型糖尿病模型,采用随机的办法将成功建模的大鼠分为胃旁路术组(GBP组)、袖状胃减容术组(SG组)、胃束带减肥术组(GLB组)和饮食控制组(AC组),分别对其施行胃旁路术、袖状胃减容术、胄束带减肥术和饮食控制。在处理前、处理后第1、4、12、24周动态观察各组大鼠体重、空腹血糖(fasting blood glucose)、糖化血红蛋白(glycosylatedhemoglobin)、胰高血糖素样肽—1(GLP—1)、葡萄糖依赖性胰岛素释放肽(GIP)的变化。
结果:GBP组大鼠术后24周存活10只,SG组大鼠术后24周存活14只,GLB组大鼠术后24周存活18只,AC组大鼠术后24周存活12只。GBP组大鼠体重在术后第4周较术前明显减轻(t=—8.195,P＜0.05):GBP组大鼠空腹血糖在术后第1周较术前下降,有统计学意义(t=—4.828,P＜0.05),同时其糖化血红蛋白的变化较术前比较也有统计学意义(t=—6.066,P＜0.05);SG组、GLB组、AC组大鼠血糖下降出现在术后第4周,与术前比较有统计学意义(P＜0.05),其术后第12周的糖化血红蛋白较术前比较有统计学意义(P＜0.05)。各组大鼠在各时相点GLP-1、GIP的变化较术前没有统计学意义(P＞0.05)。
结论:几种减重方式均能降低经STZ诱导的2型糖尿病大鼠的血糖,但以胃旁路手术效果最为显著。GBP术后血糖的下降与大鼠体重的减轻、饮食量的减少无明显关系,血糖的下降早于体重的减轻。2型糖尿病大鼠经以上四种减重方法控制血糖,不是通过改变了血中胰高血糖素样肽-1、葡萄糖依赖性胰岛素释放肽的水平起作用。减重方式特别是胃旁路术治疗2型糖尿病的作用机理尚需更进一步的研究,为临床广泛开展并最终治愈2型糖尿病提供新的理论依据。
Objective:through contract experiment in random-selected groups and research into the effect of weight controlling and blood glucose controlling with 4 ways of losing weight of Gastric By-pass,Sleeve Gastrectomy,Gastric Lap-Band and Alimentary Control working on rats to find new effective treatment of Type 2 Diabetes Mellitus and explore the relationship between the control of blood glucose and decrease of body-weight and to analyze the principle of its function.
Methods:to inject STZ into male SD rats to set objects,and randomly group the models into Gastric By-pass(GBP) group,Sleeve Gastrectomy (SG)group,Gastric Lap-Band(GLB) group and AC group and then execute Gastric By-pass,Sleeve Gastrectomy,Gastric Lap-Band and AC on them.Before and after the 1~(st),4~(th),12~(th) and 24~(th) weeks of the procedure, keeping trace of the changes of rats' weights,fasting blood glucose, glycosylated hemoglobin,GLP-land GIP.
Result:10 rats in the GBP group remain after 24 weeks of operation;14 in the SG group remain,18 in the GLB group remain;12 in the AC group remain.The weights of rats in GBP group reduce greatly(t=-8.195, P＜0.05 );The fasting blood glucose of the rats in GBP group decreases after the 1~(st) week of operation,which has its statistic meaning(-4.828, P＜0.05),and it is also of statistic meaning that the glycosylated hemoglobin change after operation(t= -6.066,P＜0.05).The blood glucose of rats in SG,GLB,AC group decrease in 4~(th) week after operation,which has its meaning(P＜0.05) compared with that before operation.And it is also of statistic meaning that compared with that before operation the glycosylated hemoglobin change in 12~(th) week after operation(P＜0.05).There is no statistic meaning in the change of GLP- 1 and GIP in the rats in each phase(P＞0.05 )
Conclusion:all these ways of reducing body-weight can reduce blood glucose of Type 2 Diabetes Mellitus rats with STZ,but the Gastric By-pass shows the most significant effect.There is no obvious relation between the decrease of blood glucose and the decrease of the rats' body-weights and the reduction of the amount of feeding.The decrease of blood glucose happens earlier than decrease of the rats' body-weights. The method of reducing the weight of Type 2 Diabetes Mellitus rats doesn't illustrate the effect of changing GLP-1 and GIP.Its functioning principle requires a further research to provide new theoretical proof for the extensive clinic operation and way of cure of Type 2 Diabetes Mellitus.
方法:对雄性SD大鼠腹腔沣射STZ建立2型糖尿病模型,采用随机的办法将成功建模的大鼠分为胃旁路术组(GBP组)、袖状胃减容术组(SG组)、胃束带减肥术组(GLB组)和饮食控制组(AC组),分别对其施行胃旁路术、袖状胃减容术、胄束带减肥术和饮食控制。在处理前、处理后第1、4、12、24周动态观察各组大鼠体重、空腹血糖(fasting blood glucose)、糖化血红蛋白(glycosylatedhemoglobin)、胰高血糖素样肽—1(GLP—1)、葡萄糖依赖性胰岛素释放肽(GIP)的变化。
结果:GBP组大鼠术后24周存活10只,SG组大鼠术后24周存活14只,GLB组大鼠术后24周存活18只,AC组大鼠术后24周存活12只。GBP组大鼠体重在术后第4周较术前明显减轻(t=—8.195,P＜0.05):GBP组大鼠空腹血糖在术后第1周较术前下降,有统计学意义(t=—4.828,P＜0.05),同时其糖化血红蛋白的变化较术前比较也有统计学意义(t=—6.066,P＜0.05);SG组、GLB组、AC组大鼠血糖下降出现在术后第4周,与术前比较有统计学意义(P＜0.05),其术后第12周的糖化血红蛋白较术前比较有统计学意义(P＜0.05)。各组大鼠在各时相点GLP-1、GIP的变化较术前没有统计学意义(P＞0.05)。
结论:几种减重方式均能降低经STZ诱导的2型糖尿病大鼠的血糖,但以胃旁路手术效果最为显著。GBP术后血糖的下降与大鼠体重的减轻、饮食量的减少无明显关系,血糖的下降早于体重的减轻。2型糖尿病大鼠经以上四种减重方法控制血糖,不是通过改变了血中胰高血糖素样肽-1、葡萄糖依赖性胰岛素释放肽的水平起作用。减重方式特别是胃旁路术治疗2型糖尿病的作用机理尚需更进一步的研究,为临床广泛开展并最终治愈2型糖尿病提供新的理论依据。
Objective:through contract experiment in random-selected groups and research into the effect of weight controlling and blood glucose controlling with 4 ways of losing weight of Gastric By-pass,Sleeve Gastrectomy,Gastric Lap-Band and Alimentary Control working on rats to find new effective treatment of Type 2 Diabetes Mellitus and explore the relationship between the control of blood glucose and decrease of body-weight and to analyze the principle of its function.
Methods:to inject STZ into male SD rats to set objects,and randomly group the models into Gastric By-pass(GBP) group,Sleeve Gastrectomy (SG)group,Gastric Lap-Band(GLB) group and AC group and then execute Gastric By-pass,Sleeve Gastrectomy,Gastric Lap-Band and AC on them.Before and after the 1~(st),4~(th),12~(th) and 24~(th) weeks of the procedure, keeping trace of the changes of rats' weights,fasting blood glucose, glycosylated hemoglobin,GLP-land GIP.
Result:10 rats in the GBP group remain after 24 weeks of operation;14 in the SG group remain,18 in the GLB group remain;12 in the AC group remain.The weights of rats in GBP group reduce greatly(t=-8.195, P＜0.05 );The fasting blood glucose of the rats in GBP group decreases after the 1~(st) week of operation,which has its statistic meaning(-4.828, P＜0.05),and it is also of statistic meaning that the glycosylated hemoglobin change after operation(t= -6.066,P＜0.05).The blood glucose of rats in SG,GLB,AC group decrease in 4~(th) week after operation,which has its meaning(P＜0.05) compared with that before operation.And it is also of statistic meaning that compared with that before operation the glycosylated hemoglobin change in 12~(th) week after operation(P＜0.05).There is no statistic meaning in the change of GLP- 1 and GIP in the rats in each phase(P＞0.05 )
Conclusion:all these ways of reducing body-weight can reduce blood glucose of Type 2 Diabetes Mellitus rats with STZ,but the Gastric By-pass shows the most significant effect.There is no obvious relation between the decrease of blood glucose and the decrease of the rats' body-weights and the reduction of the amount of feeding.The decrease of blood glucose happens earlier than decrease of the rats' body-weights. The method of reducing the weight of Type 2 Diabetes Mellitus rats doesn't illustrate the effect of changing GLP-1 and GIP.Its functioning principle requires a further research to provide new theoretical proof for the extensive clinic operation and way of cure of Type 2 Diabetes Mellitus.
引文
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2.韦丽芳,肥胖与2型糖尿病,中国医学文摘·内科学2006年第27卷第4期p352-354
3.武阳丰,马冠生,胡永华,等.中国居民的超重和肥胖流行现状,中华预防医学杂志,2005,39(5):316-320.
4.Must A,Strauss RS.Risks and consequences of childhood and adolescent obesity.Int J Obesity,1999,23 Suppl 2:S2-11.
5.Rosenbloom AL,Joe JR.Emerging epidemic of type 2 diabetes in youth.Diabetes Care,1999,22:345-354.
6.Roland S.The effects of obesity,smoking,and drinking on medical problems and costs.Health Affairs,2002,21(2):245-253.
7.DeMaria EJ,Jamal MK.Surgical options for obesity.Gastroenterol Clin North Am 2005;34:127-42.
8.NIH Conference Gastrointestinal surgery for severe obesity.Ann Int Med 1991,115:959-961.
9.Herron DM.The surgical management of severe obesity.Mt Sinai J Med,2004;71:63-71.
10.Mason EE,Ito C.Gastric bypass in obesity.Surg Clin North Am 1969;47:1345-1351.
11.Mason EE,Printen KJ,et al,Optimizing results of gastric bypass.Ann Surg,1975;182:405-414.
12.Griffen WO,Young VL,Stevenson CC.A prospective comparison of gastric and jejunoileal bypass procedures for morbid obesity.Ann Surg,1977;186:500-509.
13.MacLean LD,Rhode BM,Nohr CW.Late outcome of isolated gastric bypass. Ann Surg,2000;231:524-528.
14.Wittgrove AC,Clark GW,et al.Laparoscopic gastric bypass,Roux-en-Y:Preliminary report of five cases.Obes Surg,1994:4:353-357.
15.Higa KD,Ho T,Boone KB.Internal hernias after laparoscopic Roux-en-Y gastric bypass:incidence,treatment and prevention.Obes Surg,2003;13,350-354
16.Higa KD,Ho T,Boone KB.Laparoscopic Roux-en-Y gastric bypass:technique and 3-year follow-up.J Laparoendosc Adv Surg Tech,2001;11:282-377.
17.Marceau P,Hould FS,Simard S,et al.Biliopancreatic diversion with duodenal switch.World J Surg,1998,22:947-954.
18.Raum WJ,Martin LF.Bariatric surgery.Official Organ Of The Louisiana State Medical Society,2005;157:S65-75
19.Kuzmak LI.A reviews of seven years' experience with silicone gastric banding.Obes Surg,1991,1:403-408.
20.Belachew M,Legrand M,Vincent V,et al.Laparoscopic adjustable gastric banding.World J Surg 1998 22:955-963.
21.Favretti F,Cadiere GB,Segab G,et al.Laparoscopic adjustable gastric banding (Lap-Band):how to avoid complications.Obes Surg,1997,7:352-358.
22.Ren CJ,Horgan S,Poncc J.US experience with the LAP-BAND systcm.Am J Surg 2002,184:468-508.
23.O'Brian P,Brown W,Smith A,et al.Prospective study of a laparoscopically placed adjustable gastric band in the treatment of morbid obesity.Br J Surg,1999,85:113-118.
24.郑成竹,胡明根,柯重伟,等.腹腔镜可调节捆扎带胃减容术治疗单纯重度肥胖症的临床应用.中华胃肠外科杂志,2004;7(5):368-371.
25.Smith S,Edwards CB,Goodman GN.Changes in diabetic management after Roux-en-Y gastric bypass[J]Obes Surg,1996,6(3):345-348
26.Buehwald H,Avidor Y,Bran nwald E,et al.Bariatric surgery:a systematic review and meta-analysis[J]JAMA,2004,292(14):1724-1737
27.White S,Brooks E,Jurikova L,et al.Long-term outcomes after gastric bypass[J].Obes Surg,2005,15(2):155-163
28.Hickey MS,Pories WJ,MacDonald KG,et al.A new paradigm for Type 2diabetes mellitus:could it be a disease of the foregut?[J]Ann Surg.1998,227(5):637-644
29.Pories WJ,Albrecht RJ.Etiology of type Ⅱ diabetes mellitus:role of the foregut.World J Surg.2001;25:527-531.
30.方厚华.医学实验模型动物[M].北京:军事医学出版社,2002:28-50
31.Peluso L,Vanek VW,Efficacy of gastric bypass in the treatment of obesity-related comorbidities.[Nutr Clin Pract]2007.22(1),pp.22-8.
32..Alfonso Torquati,Rami Lutfi,Naji Abumrad,et al,Is Roux-en-Y Gastric Bypass Surgery the Most Effective Treatment for Type 2 Diabetes Mellitus in Morbidly Obese Patients? Journal of Gastrointestinal Surgery,Volume 9,Issue 8,1November 2005,P1112-1118
33.张新国 杨学军 徐红,手术治疗2型糖尿病回顾性临床研究及近期临床试用报告,中华临床医学实践杂志2005年10月第4卷第5期.P459-463
34.张士虎.苗毅,胃旁路术对非肥胖型糖尿病大鼠的降糖作用,南京医科大学学报(自然科学版),第26卷第3期,2006年3月,P176-179
35.Buchwald H,Avidor Y,Braunwald E,et al.Bariatric surgery:a systematic review and meta-analysis.JAMA 2004;292:1724-1737.
36.Rubino F.Bariatric surgery:effects on glucose homeostasis.[Curr Opin Clin Nutr Metab Care]2006 Jul;Vol.9(4),pp.497-507.
37.Pories WJ,Swanson MS,MacDonald KG,et al.Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.Ann Surg 1995;222:339-350.
38.Hickey MS,Pories WJ,MacDonald KG,et al.A new paradigm for type 2 diabetes mellitus:could it be a disease of the foregut? Ann Surg 1998;227:637-643,discussion 643-644.
39.Scopinaro N,Adami GF,Marinari GM,et al.Biliopancreatic diversion.World J Surg 1998;22:936-946.
40.Evans JL,Goldfine ID,Maddux BA,Grodsky GM.Oxidative stress and stress-activated signaling pathways:a unifying hypothesis of type 2 diabetes.Endocr Rev 2002;23:599-622.
41.Lewis GF,Carpentier A,Adeli K,Giacca A.Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes.Endocr Rev 2002;23:201-229.
42.Cummings DE,Weigle DS,Frayo RS,et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.N Engl J Med 2002;346:1623-1630.
43.Korner J,Bessler M,Cirilo LJ,et al.Effects of Roux-en-Y gastric bypass surgery on fasting and postprandial concentrations of plasma ghrelin,peptide YY,and insulin.J Clin Endocrinol Metab 2005;90:359-365.
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50.Pories WJ,Albrecht RJ.Etiology of type Ⅱ diabetes mellitus:role of the foregut.World J Surg 2001;25:527-531.
51.Rubino F,Gagner M.Potential of surgery for curing type 2 diabetes mellitus. Ann Surg 2002;236:554-559.
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54.Bittner R,Bittner B,Beget HG.Homeostasis of glucose and gastric resection:the influence of the food passage through the duodenum(article in German).Z Gastroenterol 1981;19:698-707.
2.韦丽芳,肥胖与2型糖尿病,中国医学文摘·内科学2006年第27卷第4期p352-354
3.武阳丰,马冠生,胡永华,等.中国居民的超重和肥胖流行现状,中华预防医学杂志,2005,39(5):316-320.
4.Must A,Strauss RS.Risks and consequences of childhood and adolescent obesity.Int J Obesity,1999,23 Suppl 2:S2-11.
5.Rosenbloom AL,Joe JR.Emerging epidemic of type 2 diabetes in youth.Diabetes Care,1999,22:345-354.
6.Roland S.The effects of obesity,smoking,and drinking on medical problems and costs.Health Affairs,2002,21(2):245-253.
7.DeMaria EJ,Jamal MK.Surgical options for obesity.Gastroenterol Clin North Am 2005;34:127-42.
8.NIH Conference Gastrointestinal surgery for severe obesity.Ann Int Med 1991,115:959-961.
9.Herron DM.The surgical management of severe obesity.Mt Sinai J Med,2004;71:63-71.
10.Mason EE,Ito C.Gastric bypass in obesity.Surg Clin North Am 1969;47:1345-1351.
11.Mason EE,Printen KJ,et al,Optimizing results of gastric bypass.Ann Surg,1975;182:405-414.
12.Griffen WO,Young VL,Stevenson CC.A prospective comparison of gastric and jejunoileal bypass procedures for morbid obesity.Ann Surg,1977;186:500-509.
13.MacLean LD,Rhode BM,Nohr CW.Late outcome of isolated gastric bypass. Ann Surg,2000;231:524-528.
14.Wittgrove AC,Clark GW,et al.Laparoscopic gastric bypass,Roux-en-Y:Preliminary report of five cases.Obes Surg,1994:4:353-357.
15.Higa KD,Ho T,Boone KB.Internal hernias after laparoscopic Roux-en-Y gastric bypass:incidence,treatment and prevention.Obes Surg,2003;13,350-354
16.Higa KD,Ho T,Boone KB.Laparoscopic Roux-en-Y gastric bypass:technique and 3-year follow-up.J Laparoendosc Adv Surg Tech,2001;11:282-377.
17.Marceau P,Hould FS,Simard S,et al.Biliopancreatic diversion with duodenal switch.World J Surg,1998,22:947-954.
18.Raum WJ,Martin LF.Bariatric surgery.Official Organ Of The Louisiana State Medical Society,2005;157:S65-75
19.Kuzmak LI.A reviews of seven years' experience with silicone gastric banding.Obes Surg,1991,1:403-408.
20.Belachew M,Legrand M,Vincent V,et al.Laparoscopic adjustable gastric banding.World J Surg 1998 22:955-963.
21.Favretti F,Cadiere GB,Segab G,et al.Laparoscopic adjustable gastric banding (Lap-Band):how to avoid complications.Obes Surg,1997,7:352-358.
22.Ren CJ,Horgan S,Poncc J.US experience with the LAP-BAND systcm.Am J Surg 2002,184:468-508.
23.O'Brian P,Brown W,Smith A,et al.Prospective study of a laparoscopically placed adjustable gastric band in the treatment of morbid obesity.Br J Surg,1999,85:113-118.
24.郑成竹,胡明根,柯重伟,等.腹腔镜可调节捆扎带胃减容术治疗单纯重度肥胖症的临床应用.中华胃肠外科杂志,2004;7(5):368-371.
25.Smith S,Edwards CB,Goodman GN.Changes in diabetic management after Roux-en-Y gastric bypass[J]Obes Surg,1996,6(3):345-348
26.Buehwald H,Avidor Y,Bran nwald E,et al.Bariatric surgery:a systematic review and meta-analysis[J]JAMA,2004,292(14):1724-1737
27.White S,Brooks E,Jurikova L,et al.Long-term outcomes after gastric bypass[J].Obes Surg,2005,15(2):155-163
28.Hickey MS,Pories WJ,MacDonald KG,et al.A new paradigm for Type 2diabetes mellitus:could it be a disease of the foregut?[J]Ann Surg.1998,227(5):637-644
29.Pories WJ,Albrecht RJ.Etiology of type Ⅱ diabetes mellitus:role of the foregut.World J Surg.2001;25:527-531.
30.方厚华.医学实验模型动物[M].北京:军事医学出版社,2002:28-50
31.Peluso L,Vanek VW,Efficacy of gastric bypass in the treatment of obesity-related comorbidities.[Nutr Clin Pract]2007.22(1),pp.22-8.
32..Alfonso Torquati,Rami Lutfi,Naji Abumrad,et al,Is Roux-en-Y Gastric Bypass Surgery the Most Effective Treatment for Type 2 Diabetes Mellitus in Morbidly Obese Patients? Journal of Gastrointestinal Surgery,Volume 9,Issue 8,1November 2005,P1112-1118
33.张新国 杨学军 徐红,手术治疗2型糖尿病回顾性临床研究及近期临床试用报告,中华临床医学实践杂志2005年10月第4卷第5期.P459-463
34.张士虎.苗毅,胃旁路术对非肥胖型糖尿病大鼠的降糖作用,南京医科大学学报(自然科学版),第26卷第3期,2006年3月,P176-179
35.Buchwald H,Avidor Y,Braunwald E,et al.Bariatric surgery:a systematic review and meta-analysis.JAMA 2004;292:1724-1737.
36.Rubino F.Bariatric surgery:effects on glucose homeostasis.[Curr Opin Clin Nutr Metab Care]2006 Jul;Vol.9(4),pp.497-507.
37.Pories WJ,Swanson MS,MacDonald KG,et al.Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.Ann Surg 1995;222:339-350.
38.Hickey MS,Pories WJ,MacDonald KG,et al.A new paradigm for type 2 diabetes mellitus:could it be a disease of the foregut? Ann Surg 1998;227:637-643,discussion 643-644.
39.Scopinaro N,Adami GF,Marinari GM,et al.Biliopancreatic diversion.World J Surg 1998;22:936-946.
40.Evans JL,Goldfine ID,Maddux BA,Grodsky GM.Oxidative stress and stress-activated signaling pathways:a unifying hypothesis of type 2 diabetes.Endocr Rev 2002;23:599-622.
41.Lewis GF,Carpentier A,Adeli K,Giacca A.Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes.Endocr Rev 2002;23:201-229.
42.Cummings DE,Weigle DS,Frayo RS,et al.Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.N Engl J Med 2002;346:1623-1630.
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