糖尿病大鼠胃动力变化与胃血管变化关系的研究
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摘要
目的：研究糖尿病胃动力变化与胃血管变化的关系。
方法：72只SPF级雄性Wistar大鼠适应性喂养一周,随机分为实验组和对照组,实验组动物采用高脂高糖饲料喂养诱导并小剂量链脲佐菌素(STZ)注射破坏胰岛β细胞,制造2型糖尿病模型。分别于4周,24周时应用单光子发射断层显像仪(SPECT)技术测定胃排空,观察血内皮素(ET-1)、血栓调节蛋白(TM)、血管性假性血友病因子(vWF),并在显微镜下观察胃血管的病理变化。
结果：24周模型组大鼠血浆TM、vWF、ET-1显著升高,4周模型组轻度升高。显微镜观察见早期血管内皮轻度损害,微血管代偿性增加,胃动力加快。随着病程进展,血管内皮损害进一步加重,胃粘膜微血管逐渐减少,毛细血管扩张,粘膜下及肌层小血管管壁增厚,管腔狭窄,管壁／管腔比值明显增大,胃动力延缓。
结论：糖尿病胃动力变化与胃血管变化相关,并且血管病变可能是引起胃动力变化的始动因素。
Objective:To investigate the correlative of the gastric motility change and gastric vasal change in type 2 diabetic rats. Methods:72 male SPF Wistar rats were first divided random into two groups:control (n=24) and diabetic group (n=48). The control was fed ordinary laboratory diet for 20 weeks, but the diabe-tic group was fed fat-and caloric-rich laboratory diet for 6 weeks and then inject-ed with small dose of streptozotocin(30mg/kg), until 24weeks to develop diabet-ic gastric motility disorders model. Gastric emptying was measured by SPECT after 4,24weeks either. In addition observing plasma endothelin (ET-1), thromb-omodulin (TM), vWillebrand factor (vWF), and observed under a microscope, the gastric peripheral vascular and microvascular pathological changes. Results: The plasma TM, vWF, ET-1 increased significantly in 24 weeks and increased slightly in 4 weeks. Early microvascular compensatory increase, and gastric motility speed up. As the illness progresses, gastric microvascular diminishing、telangiectasia、small vessel wall thickening in submucosal and muscular layers、stenosis、wall/lumen ratio significantly increased. Conclusion:The vascular changes associated with changes in gastric motility in diabetes.
方法：72只SPF级雄性Wistar大鼠适应性喂养一周,随机分为实验组和对照组,实验组动物采用高脂高糖饲料喂养诱导并小剂量链脲佐菌素(STZ)注射破坏胰岛β细胞,制造2型糖尿病模型。分别于4周,24周时应用单光子发射断层显像仪(SPECT)技术测定胃排空,观察血内皮素(ET-1)、血栓调节蛋白(TM)、血管性假性血友病因子(vWF),并在显微镜下观察胃血管的病理变化。
结果：24周模型组大鼠血浆TM、vWF、ET-1显著升高,4周模型组轻度升高。显微镜观察见早期血管内皮轻度损害,微血管代偿性增加,胃动力加快。随着病程进展,血管内皮损害进一步加重,胃粘膜微血管逐渐减少,毛细血管扩张,粘膜下及肌层小血管管壁增厚,管腔狭窄,管壁／管腔比值明显增大,胃动力延缓。
结论：糖尿病胃动力变化与胃血管变化相关,并且血管病变可能是引起胃动力变化的始动因素。
Objective:To investigate the correlative of the gastric motility change and gastric vasal change in type 2 diabetic rats. Methods:72 male SPF Wistar rats were first divided random into two groups:control (n=24) and diabetic group (n=48). The control was fed ordinary laboratory diet for 20 weeks, but the diabe-tic group was fed fat-and caloric-rich laboratory diet for 6 weeks and then inject-ed with small dose of streptozotocin(30mg/kg), until 24weeks to develop diabet-ic gastric motility disorders model. Gastric emptying was measured by SPECT after 4,24weeks either. In addition observing plasma endothelin (ET-1), thromb-omodulin (TM), vWillebrand factor (vWF), and observed under a microscope, the gastric peripheral vascular and microvascular pathological changes. Results: The plasma TM, vWF, ET-1 increased significantly in 24 weeks and increased slightly in 4 weeks. Early microvascular compensatory increase, and gastric motility speed up. As the illness progresses, gastric microvascular diminishing、telangiectasia、small vessel wall thickening in submucosal and muscular layers、stenosis、wall/lumen ratio significantly increased. Conclusion:The vascular changes associated with changes in gastric motility in diabetes.
引文
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[3]Lidums I, Hebbard GS, Holloway RH. Effect of atropine on prox—imal gastric motor and sensory function in normal subjects. Gut,2000,47: 30—36.
[4]李皓旭,秦晓民,鲁彦,等.糖尿病胃轻瘫发病机制.胃肠病和肝病学杂志,2003,12：88—90.
[5]刘剑峰,杨毅,梁延杰,等.糖尿病大鼠胃窦部CGRP、VIP神经免疫组织化学及图像分析.中国糖尿病杂志,1996,4：167—169.
[6]Fraser RJ, Horowitz M, Maddox AF, et alHyperglycaemia slows gastric empting in type 1 diabetic mellitus[J]Diabetologia,1990,33:675.
[7]蓝宇,柯美云,朱朝晖,等.糖尿病不同阶段胃运动功能的临床研究[J]中华消化杂志,2001,21(12)：716.
[8]陈建,李君曼,李学会,等.糖尿病胃轻瘫患者的胃排空延迟与胃肠激素变化相关性探讨[J]山东医药,1997,37(6)：9.
[9]张亚萍,张宽学,罗金燕.糖尿病大鼠肠道Cajal间质细胞结构变化的研究[J]中华内科杂志,200241(5)：310.
[10]李秀钧主编.2001.胰岛素抵抗综合症[M].北京：人民卫生出版社.
[11]Lupi R, Dotta F, Marselli L et al.2002. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets. Diabetes.51:1437-1442.
[12]李晨钟,张素华,舒昌达,等.用高脂肪膳食复制胰岛素抵抗大鼠模型.基础医学与临床,2000,20：93-95.
[13]杨架林,李果,刘优萍.2003.长期高脂饮食加小剂量链脲霉素建立人类普通2型糖尿病大鼠模型的研究.中国实验动物学报,11(3)：138-141.
[14]olond iL, Bo rtolottoi M, San ti Vet alMeasu rement of gastric emptying by real time ultrasonog rap hyGastroenterology,1985,89:752.
[15]Schwizer W, Meecke H, Fried MMeasurement of gastric emptying by magnetic resonance imaging in humans[J]Gastroenterology,1992,103:369.
[16]Avill R, Mangnall YF, Bird NC et alApplied potential tomography:a new noninvasive technique for measuring gastric emptying [J]Gastroenterology, 1987,92 (4):1019-1026.
[17]张新华,严祥,赵丽,等.孤啡肽对糖尿病胃轻瘫大鼠胃动力的影响,第四军医大学学报,2008,29(9).
[18]潘琳主编.实验性糖尿病病理图谱[M].北京：科学出版社,2007：186-198.
[19]王宏宇主编.血管病学[M].北京：人民军医出版社,2006.6,3-8.
[20]Hwang SJ, BallantyneCM, Sharrett AR, et al. Cirdulating adhesion molecules VCAM-1,ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases:the Atherosclerosis Risk In Communities(ARIC)study. Circulation 1997:96(12):631-638).
[21]Schiffrin EL. Touyz RM. Multiple actions of angiotensin Ⅱ in hypertension:Benefits of AT1 receptor blockade. J Am Coll Cardiol 2003:42:911-913.
[22]Kessler L, Wiesel ML, Attali P, et al. [J]. Diabetes Metab,1998,24(4):327-336.
[23]Yokota H, Naoe Y, Nakabayashi M, et al. [J]. Neurotrauma,2002,19(9):1007-1015.
[24]Califano F, Giovannie T, Pantone P, et al. [J]. Eur Rev Med Pharmacol Sci,2000,4(3):59-66.
[25]Nomura S,Shouzu A, Omoto S, et al. [J].Thromb Haemost,1998,80(3):388-392.
[26]Boffa MC, Karmochkine M. Thrombomodulin:an overview and potential implications in vascular disorders. Lupus,1998,7(suppl 2):S120-S125.
[27]周丽诺,朱禧星.Ⅱ型糖尿病人血浆内皮素-Ⅰ含量增值的临床意义[J]上海医科大学学报.1994,21(6)：437.
[28]阮长武,范宗华,杨俊敏,等.老年糖尿病患者血浆内皮素水平变化及其临床意义[J].中华内分泌代谢杂志,1995,11(4)：238.
[29]De La Cruz J P, Moreno A, Guerrero A, et al. Nitric oxide2cGMP and prostacyclin2 cAMP pathways in patients with type II diabetes and different types of retinopathy [J]. Pathophysiol Haemost Thromb,2002,32(1):25-32.
[30]Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin dependent) diabetes mellitus[J].Diabetologia,1989;32:151-159.
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