不同肠段小肠旷置术对2型糖尿病大鼠血糖控制的作用

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

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8cm，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／dl比（145±35）mg／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。

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 duodenum 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 （HbAlc） 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 HbAlc 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.