不同肠段小肠旷置术对2型糖尿病大鼠血糖控制的作用

目的 观察不同肠段小肠旷置术对2型糖尿病大鼠的治疗作用.方法 40只自发性糖尿病Goto-Kakizaki(GK)大鼠随机分为胃空肠始端Roux-en-Y吻合组(旷置十二指肠,A组),胃空肠近端Roux-en-Y吻合组(旷置十二指肠和近端空肠8 cm,B组),胃回肠始端Roux-en-Y吻合组(旷置十二指肠和全部空肠,C组),胃回肠中段Roux-en-Y吻合组(旷置次全小肠,D组)和假手术组(SO组)5组,每组8只.检测术前,术后1、3、6、12、24周各组空腹血糖水平;测定术前,术后12、24周各组糖化血红蛋白水平.结果 与术前比较,A～D组术后1、3、6、12、24周空腹血糖,12、24周糖化血红蛋白均明显降低B组术前和术后1周空腹血糖分别为(162±44)mg/dl和(80±19) mg/dl,术前和术后12周糖化血红蛋白分别为(8.2±2.2)%和(5.1±1.5)%,P＜0.05或P＜0.01];而SO组空腹血糖术后1、3、6周均未发生明显变化(均P＞0.05),术后12、24周均显著高于术前(164±44) mg/dl、(180±42) mg/all比(145±35)ms/dl,均P＜0.01],糖化血红蛋白术后12、24周未发现明显变化(均P＞0.05).A～D组术后1、3、6、12、24周空腹血糖,12、24周糖化血红蛋白均显著低于SO组(P＜0.05或P＜0.01).B组术后1、3、6、12、24周空腹血糖,12、24周糖化血红蛋白均显著低于A组术后24周空腹血糖(82±21) mg/dl比(111±27) mg/dl,糖化血红蛋白(3.9±0.9)%比(5.4±1.2)%,均P＜0.05],对血糖控制效果优于A组;但与C组和D组相比差异均无统计学意义(均P＞0.05).结论 仅从血糖控制效果方面评估,不同肠段小肠旷置术对大鼠2型糖尿病均有治疗作用,其中旷置十二指肠和近端空肠效果最佳,前肠假说可能在2型糖尿病致病机制中起主要作用.

Effect of blood glucose control after small intestine exclusion surgery in Goto-Kakizaki rat with type 2 diabetes mellitus

Objective To evaluate the effect of diabetic control after small intestine exclusion surgery in Goto-Kakizaki (GK) rat with type 2 diabetes mellitus.Methods GK type 2 diabetic rats underwent duodenal bypass (Group A,n=8) creating a shortcut for ingested nutrients with bypassing duodenum alone,or duodenal-jejunal bypass (Group B,n=8),a stomach-preserving RYGB excluding duodenum and proximal jejunum,or duodeuum and total jejunum exclusion (Group C,n=8),or sub-total small intestine exclusion (Group D,n=8) creating a shortcut for ingested nutrients with bypassing duodenum,jejunum and sub-total ileum.Controls were pair-fed (PF) sham-operated and untreated GK rats (Group SO,n=8).Rats were observed for 24 weeks after surgery.Fasting blood glucose (FBG) level was determined on a Surestep plus blood glucose meter (Lifescan) at 0,1,3,6,12,24 week.Hemoglobin Alc (HbA1c) level was measured at 0,12,24 week on VARIANT Hemoglobin Alc Program (Bio-Ray) with high performance liquid chromatography (HPLC) method.Results The fasting blood glucose and HbAlc levels significantly decreased after surgery in all the operative groups through the entire follow-up period Group B (FBG before surgery and 1 week after:(162±44) mg/dl vs (80±19) mg/dl;HbAlc before surgery and 12 week after:(8.2±2.2)% vs (5.1±1.5)%,P＜0.05 or P＜0.01];while FBG had no differences before 12 week and significantly increased at 12 week (164±44) mg/dl and 24 week (180±42) mg/dl in group SO preoperative (145±35) mg/dl,P＜0.01].As compared with shamoperated rats,all the operative groups showed reduced blood-glucose and HbAlc levels through the entire follow-up period (P＜0.05 or P＜0.01).The FBG and HbA1c levels in Group B significantly decreased versus Group A 24 week (FBG:(82±21) mg/dl vs (111±27) mg/dl;HbAlc:(3.9±0.9)% vs (5.4±1.2)%,P＜0.05],indicating that duodenal-jejunal bypass had markedly a better effect of diabetic control.But Groups B,C and D were similar to one another (P＞0.05),suggesting that a potential role of proximal gut in the pathogenesis of disease.Conclusion In spontaneous type 2 diabetes mellitus rats,all the small intestinal exclusion including proximal gut are effective in glucose control.In terms of intestinal nutrient absorption,duodenal-jejunal bypass may be an ideal surgery for clinical diabetic control.These findings suggest a potential role of proximal intestine in pathogenesis of type 2 diabetes mellitus.