改良型十二指肠旷置术对2型糖尿病大鼠糖代谢的影响

doi:10.12300/j.issn.1674-5817.2024.056

实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (5): 523-530.DOI: 10.12300/j.issn.1674-5817.2024.056

改良型十二指肠旷置术对2型糖尿病大鼠糖代谢的影响

杨劲¹()(), 俞诗雅², 林楠¹^,², 方永超¹, 赵虎¹, 邱锦维², 林鸿铭², 陈惠燕², 王瑜¹, 吴伟航¹^,²()()

^1.联勤保障部队第九〇〇医院普通外科, 福州 350000
^2.福建医科大学福总临床医学院普通外科, 福州 350000

收稿日期:2024-04-17 修回日期:2024-07-16 出版日期:2024-11-06 发布日期:2024-10-25
通讯作者: 吴伟航（1990—），男，博士研究生，主治医师，研究方向：胃肠道肿瘤的分子机制、早期诊断和营养学治疗。E-mail： 454646066@qq.com。ORCID：0000-0002-7335-6388
作者简介:杨劲（1993—），男，硕士，住院医师，研究方向：胃肠疾病、代谢与减重外科治疗。E-mail: 766753548@qq.com。ORCID：0000-0002-8454-283X

Effect of Modified Duodenal Exclusion Surgery on Glucose Metabolism in Rats with Type 2 Diabetes Mellitus

YANG Jin¹()(), YU Shiya², LIN Nan¹^,², FANG Yongchao¹, ZHAO Hu¹, QIU Jinwei², LIN Hongming², CHEN Huiyan², WANG Yu¹, WU Weihang¹^,²()()

^1.Department of General Surgery, 900th Hospital of Joint Logistics Support Force, PLA, Fuzhou 350000, China
^2.Fuzong Clinical Medical College, Fujian Medical University, Fuzhou 350000, China

Received:2024-04-17 Revised:2024-07-16 Published:2024-10-25 Online:2024-11-06
Contact: WU Weihang (ORCID: 0000-0002-7335-6388), E-mail: 454646066@qq.com

摘要/Abstract

摘要：

目的探讨防反流的改良型十二指肠旷置术对2型糖尿病（type 2 diabetes mellitus，T2DM）大鼠糖代谢的影响，明确十二指肠在维持葡萄糖稳态中的作用。方法取40只5周龄的雄性SD大鼠，通过高脂饲料喂养联合低剂量链脲霉素诱导T2DM。将36只达到T2DM模型标准的大鼠随机分为3组：单纯十二指肠旷置术组（DE组）、防反流的改良型十二指肠旷置术组（MDE组）及假手术组（SO组），每组12只。术后第4周行胃肠道造影，并分别于术前及术后1、2、4、8周检测各组大鼠的体重、空腹血糖浓度、血清胰高血糖素样肽-1（glucagon-like peptide-1，GLP-1）浓度；术后8周处死大鼠，取每组大鼠胆胰袢1 cm肠段，行病理切片的苏木精-伊红（hematoxylin and eosin，HE）染色后在光学显微镜下观察肠黏膜绒毛长度。结果胃肠造影显示DE组中造影剂明显向十二指肠肠腔反流，而MDE组未见反流现象。术后1周，3组大鼠的体重较术前均短暂性显著下降（P<0.05），之后各组大鼠体重均随时间增长，组间体重无显著差异（P>0.05）。与SO组比较，MDE组和DE组术后各个时间点的空腹血糖浓度明显下降（P<0.05），GLP-1浓度显著升高（P<0.05）；MDE组术后各个时间点的空腹血糖浓度均比DE组低（P<0.05），但MDE组和DE组之间术后各个时间点的血清GLP-1浓度无显著差异（P>0.05）。在肠黏膜形态学上，MDE组大鼠的胆胰袢黏膜绒毛长度均明显短于DE组和SO组（P<0.05）。结论防反流的改良型十二指肠旷置术可以有效改善T2DM大鼠的糖代谢，避免食糜向旷置的十二指肠反流，从而加强其降糖作用。

关键词: 十二指肠旷置术, 2型糖尿病, 血糖, 胃肠造影, 肠绒毛, 大鼠

Abstract:

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. Methods Forty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Key words: Duodenal exclusion surgery, Type 2 diabetes mellitus, Blood glucose, Gastroenterography, Intestinal villi, Rats

中图分类号:

R-332

杨劲,俞诗雅,林楠,等. 改良型十二指肠旷置术对2型糖尿病大鼠糖代谢的影响[J]. 实验动物与比较医学, 2024, 44(5): 523-530. DOI: 10.12300/j.issn.1674-5817.2024.056.

YANG Jin,YU Shiya,LIN Nan,et al. Effect of Modified Duodenal Exclusion Surgery on Glucose Metabolism in Rats with Type 2 Diabetes Mellitus[J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 523-530. DOI: 10.12300/j.issn.1674-5817.2024.056.

图/表 4

图1 单纯十二指肠旷置术（DE）组和防反流十二指肠旷置术（MDE）组大鼠的手术示意图注：A，DE组手术示意图；B，MDE组手术示意图；C，采用直径约2 mm、长约4 cm硅胶管制成的十二指肠肠腔套管，头端标示显影条，便于造影中识别；D，将硅胶套管一端缝合固定于肠壁，可见胆胰液从硅胶管通畅流出；E，单纯十二指肠旷置后吻合结束，于胆胰袢及胆胰袢和共同袢的吻合口处标记显影条，便于术后造影中识别胆胰袢。

Figure 1 Surgical illustrations of rats in the duodenum exclusion (DE) group and the modified duodenal exclusion (MDE) group with anti-refluxNote：A, Schematic diagram of the surgical procedure for the DE group. B, Schematic diagram of the surgical procedure for the MDE group. C, Duodenal intestinal lumen tubes made of silicone tubing of about 2 mm in diameter and 4 cm in length, with the head end labeled with a contrast strip for easy identification in imaging. D, One end of the silicone tube was sutured to the intestinal wall, allowing biliopancreatic fluid to flow smoothly from the silicone tube. E, End of the anastomosis after simple duodenal exclusion surgery, with contrast strips marking the biliopancreatic loop and the anastomosis of biliopancreatic loop and common loop to facilitate the identification in postoperative imaging.

图2 DE组及MDE组大鼠术后胃肠造影和体重变化注：A，单纯十二指肠旷置（DE）组术后的胃肠造影图（图中箭头所示为胆胰袢，可见造影剂反流至胆胰袢中）；B，单纯十二指肠旷置+套管置入（MDE）组术后的胃肠造影图（箭头所示为套管置入的胆胰袢，未见造影剂反流至胆胰袢征象）；C，三组大鼠术后的体重变化（SO，假手术；ns，差异无统计学意义；SO、DE和MDE组大鼠分别为12、11和10只）。

Figure 2 Postoperative gastroenterography and body weight changes in DE and MDE rat groupsNote：A, Postoperative gastroenterography of simple duodenal exclusion (DE group, n=11) (the arrow indicates the biliopancreatic loop, with visible contrast reflux into the loop). B, Postoperative gastroenterography of simple duodenal exclusion + tube placement (MDE group, n=10) (the arrow indicates the biliopancreatic loop with inserted tube, with no contrast reflux observed). C, Postoperative body weight changes in three groups of rats (SO, Sham operation, n=12; ns, No statistical difference).

图3 3组大鼠术前、术后不同时间点的空腹血糖和GLP-1浓度变化注：A，3组大鼠术前、术后不同时间点的空腹血糖变化折线图和柱形图；B，3组大鼠术前、术后不同时间点GLP-1的变化折线图和柱形图。SO组，假手术组，n=12；DE组，单纯十二指肠旷置组，n=11；MDE组，单纯十二指肠旷置+置管/防反流组，n=10。ns，差异无统计学意义。*表示P<0.05，**表示P<0.01，***表示P<0.001，****表示P<0.000 1。

Figure 3 Changes in fasting glucose and GLP-1 levels in the three groups of rats at different time points before and after surgeryNote：A, Line graphs and bar charts showing the changes in fasting glucose levels of the three groups of rats at different time points before and after surgery. B, Line graphs and bar charts of changes in GLP-1 levels at different time points pre- and post-operatively in the three groups of rats. SO group, Sham operation group, n=12; DE group, Simple duodenal exclusion group, n=11; MDE group, Simple duodenal exclusion with tube placement/anti-reflux group, n=10. ns, No statistical difference. * indicates P<0.05, **indicates P<0.01, ***indicates P<0.001,****indicates P<0.000 1.

图4 3组大鼠术后8周后的胆胰袢肠黏膜绒毛形态图（HE染色，×100）注：SO，假手术组，n=12；DE，单纯十二指肠旷置组，n=11；MDE，单纯十二指肠旷置+置管/防反流组，n=10。ns，差异无统计学意义。*表示P<0.05。

Figure 4 Morphology of intestinal mucosal villi of biliopancreatic collaterals in three groups of rats after 8 weeks （HE staining， ×100）Note：SO, Sham operation group, n=12; DE, Simple duodenal exclusion group, n=11; MDE, Simple duodenal exclusion with tube placement/anti-reflux group, n=10. ns, No statistical difference. *indicates P<0.05.

参考文献 17

1	WANG L M, GAO P, ZHANG M, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013[J]. JAMA, 2017, 317(24):2515-2523. DOI: 10.1001/jama.2017.7596 .
2	MINGRONE G, PANUNZI S, GAETANO A D, et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial[J]. Lancet, 2021, 397(10271):293-304. DOI: 10.1016/S0140-6736(20)32649-0 .
3	YOSHINO M, KAYSER B D, YOSHINO J, et al. Effects of diet versus gastric bypass on metabolic function in diabetes[J]. N Engl J Med, 2020, 383(8):721-732. DOI: 10.1056/NEJMoa2003697 .
4	MINGRONE G, PANUNZI S, GAETANO A D, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes[J]. N Engl J Med, 2012, 366(17):1577-1585. DOI: 10.1056/NEJMoa1200111 .
5	高相楠, 高宏凯, 张利岩, 等. 腹腔镜胃转流术对体质指数28～35 kg/m²伴代谢综合征的2型糖尿病患者的疗效研究[J]. 中国全科医学, 2015, 18(8):906-910. DOI: 10.3969/J.iSSn.1007-9572.2015.08.012 .
	GAO X N, GAO H K, ZHANG L Y, et al. Efficacy of laparoscopic gastric bypass operation on type 2 diabetic mellitus patients with body mass index 28-35 kg/m² accompanied by metabolic syndrome[J]. Chin Gen Pract, 2015, 18(8):906-910. DOI: 10.3969/J.iSSn.1007-9572.2015.08.012 .
6	张振,宫轲. 外科治疗糖尿病的主要手术方式及其机制[J].首都医科大学学报, 2015, 36(2):318-323. DOI: 10.3969/j.issn.1006-7795.2015.02.029 .
	ZHANG Z, GONG K. Main surgery procedures and mechanisms for treating type 2 diabetes[J]. J Cap Med Univ, 2015, 36(2):318-323. DOI: 10.3969/j.issn.1006-7795.2015.02.029 .
7	吴春兴, 王小芳, 谢斐. 参麦注射液治疗稳定性心绞痛合并2型糖尿病患者的临床疗效观察[J]. 医学临床研究, 2019, 36(1):148-149, 154. DOI: 10.3969/j.issn.1671-7171.2019.01.050 .
	WU C X, WANG X F, XIE F. Clinical observation of Shenmai injection in the treatment of patients with stable angina pectoris complicated with type 2 diabetes mellitus[J]. J Clin Res, 2019, 36(1):148-149, 154. DOI: 10.3969/j.issn.1671-7171.2019.01.050 .
8	ANGRISANI L, SANTONICOLA A, IOVINO P, et al. Bariatric surgery and endoluminal procedures: IFSO worldwide survey 2014[J]. Obes Surg, 2017, 27(9):2279-2289. DOI: 10.1007/s11695-017-2666-x .
9	THALER J P, CUMMINGS D E. Minireview: Hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery[J]. Endocrinology, 2009, 150(6):2518-2525. DOI: 10.1210/en.2009-0367 .
10	王瑜, 张再重, 王烈, 等. 不同肠段小肠旷置术对非肥胖型2型糖尿病大鼠的治疗作用[J]. 中华外科杂志, 2009, 47(22):1736-1740. DOI: 10.3760/cma.j.issn.0529-5815.2009.22.016 .
	WANG Y, ZHANG Z C, WANG L, et al. Effect of diabetes control after small intestine exclusion surgery in Goto-Kakizaki rat with non-obese type 2 diabetes mellitus[J]. Chin J Surg, 2009, 47(22):1736-1740. DOI: 10.3760/cma.j.issn.0529-5815.2009.22.016 .
11	DE JONGE C, RENSEN S S, VERDAM F J, et al. Endoscopic duodenal-jejunal bypass liner rapidly improves type 2 diabetes[J]. Obes Surg, 2013, 23(9):1354-1360. DOI: 10.1007/s11695-013-0921-3 .
12	陈济华, 陈鑫. 十二指肠空肠套管治疗肥胖和2型糖尿病的研究进展[J]. 中华消化内镜杂志, 2021, 38(6):496-500. DOI: 10.3760/cma.j.cn321463-20200716-00325 .
	CHEN J H, CHEN X. The researching progress of duodenal-jejunal bypass sleeve in treating obesity and type 2 diabetes[J]. Chin J Dig Endosc, 2021, 38(6):496-500. DOI: 10.3760/cma.j.cn321463-20200716-00325 .
13	陈鑫, 刘彬, 喻敏, 等. 十二指肠腔内套管置入术改善非肥胖型2型糖尿病大鼠糖代谢的作用[J]. 中华内分泌外科杂志, 2013, 7(6):447-450, 477. DOI: 10.3760/cma.j.issn.1674-6090.2013.06.002 .
	CHEN X, LIU B, YU M, et al. Duodenal endoluminal sleeve improves glucose metabolism of non-obese type 2 diabetic rats[J]. Chin J Endocr Surg, 2013, 7(6):447-450, 477. DOI: 10.3760/cma.j.issn.1674-6090.2013.06.002 .
14	黄盛, 焦亚彬, 王瑜, 等. 胃转流术治疗非肥胖型2型糖尿病大鼠的长期疗效观察[J]. 中华临床医师杂志(电子版), 2011, 5(5):1313-1317. DOI: 10.3877/cma.j.issn.1674-0785.2011.05.011 .
	HUANG S, JIAO Y B, WANG Y, et al. Long-term efficacy of gastric bypass on non-obese type 2 diabetes mellitus in Goto-Kakizaki rat[J]. Chin J Clin Electron Ed, 2011, 5(5):1313-1317. DOI: 10.3877/cma.j.issn.1674-0785.2011.05.011 .
15	SUN D, LIU S Z, ZHANG G Y, et al. Type 2 diabetes control in a nonobese rat model using sleeve gastrectomy with duodenal-jejunal bypass (SGDJB)[J]. Obes Surg, 2012, 22(12):1865-1873. DOI: 10.1007/s11695-012-0744-7 .
16	李贝贝. GLP1药物治疗2型糖尿病与早期胰岛素治疗2型糖尿病的临床效果及对血糖影响的比较[J]. 中文科技期刊数据库(全文版)医药卫生, 2022(7):52-55.
	LI B B. Comparison of clinical effects and blood sugar effects between GLP1 drugs and early insulin in the treatment of type 2 diabetes mellitus[J]. Chinese Science and Technology Journal Database (Full-text Edition) Medical and Health, 2022(7):52-55.
17	梅承翰, 陈蓓蓓. 胰高血糖素样肽1类似物对阿尔兹海默症的神经保护作用及机制研究进展[J]. 实验动物与比较医学, 2023, 43(2): 186-193. DOI:10.12300/j.issn.1674-5817.2022.136 .
	MEI C H, CHEN B B. Research progress on neuroprotective effects and mechanisms of glucagon-likepeptide 1 analogues in Alzheimer's disease[J]. Lab Anim Comp Medicine, 2023, 43(2): 186-193. DOI:10.12300/j.issn.1674-5817.2022.136 .

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改良型十二指肠旷置术对2型糖尿病大鼠糖代谢的影响

Effect of Modified Duodenal Exclusion Surgery on Glucose Metabolism in Rats with Type 2 Diabetes Mellitus

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