【作者】 李孟彬；

【导师】 李开宗； 王为忠；

【作者基本信息】 第四军医大学 ， 外科学（普通外科）， 2001， 硕士

【摘要】 在小肠移植（SBT）中，移植肠粘膜对缺血再灌注损伤比较敏感，易受到损害，缺血时间越长，移植肠粘膜结构的破坏越严重。同时，由于小肠移植术后早期移植肠功能尚未恢复，需要一段时间的全肠外营养（TPN）支持，长期的TPN也会导致小肠粘膜结构的损伤、细菌易位，从而影响移植肠功能的恢复。现已有大量研究表明，左型精氨酸（L-Arg）能够提高机体一氧化氮（NO）的水平，而NO在小肠移植缺血再灌注损伤中可以保护小肠粘膜以减轻移植肠的损害，促进移植肠功能的恢复。谷氨酰胺（Gln）作为一种肠道粘膜细胞代谢必需的营养物质，对维持肠道粘膜上皮细胞完整性和促进小肠粘膜结构的修复起着十分重要的作用。本实验旨在探讨L-Arg和力肽在小肠移植缺血再灌注损伤中的治疗作用和协同效应。 方法：建立大鼠小肠移植缺血再灌注损伤模型。实验分为两部分：一、SD大鼠32只，随机分为对照组（Control组n=16）和小肠移植组（SBT组n=2×8），于血流恢复后20min、术后1天剖杀取材。二、SD大鼠112只随机分为四组：1．对照组（Control组n=16），行虚拟手术，普通饲料；2．SBT+标准TPN组（sTPN组n=2×16）；3．SBT+力肽+TPN组（dTPN组n=2×16）；4．SBT+L-Arg+力肽+TPN组（aTPN组n=2×16），分别于术后4、8d剖杀取材。检测血浆Gln水平，小肠NO、MDA、Gln的含量及小肠粘膜形态学改变。 结果：1．大鼠移植肠血流恢复后粘膜MDA水平立即升高，显著高于对照组（P＜0.01），然后逐渐降低，aTPN组术后4d降至正常，sTPN组及dTPN组术后8d降至正常；2．移植肠粘膜NO含量于血流恢复20min后明 第四军医大学硕土学位论文显低于对照组（P＜0刀1），术后m恢复正常，STPN及 dTPN组术后 4、sd肠粘膜NO水平与对照组无差异，而aTPN组术后4、sd移植肠粘膜NO水平均明显高于对照组（P＜0刀1，P＜0刀1）；3．盯PN及盯PN组血浆、肠粘膜Gin的浓度及绒毛高度、粘膜厚度均显著高于sTPN组，说明力肽能够促进移植肠粘膜的修复；4．术后4d，aTPN组移植肠粘膜＊ 浓度0功刀5入绒毛高度（P＜0刀5）高于d＊PN组，术后sd无差异。 结论：1．力肽能够维持和升高血浆、肠粘膜m 的水平。2．TPN过程中加用力肽有利于移植肠粘膜结构的修复＊．L－ATg可以提高大鼠移植肠粘膜NO的水平／．L－Axg对力肽的吸收及促进肠粘膜修复的作用有协同效应。更多还原

【Abstract】 In small bowel transplantation(SBT), the graft mucosa is much sensitive to ischemialreperfusion injure and impairment will likely occur which intensifies with time. Besides, long-term total parenteral nutrition (TPN), which is necessary for supporting functional recovery of early stage SBT, will also lead to mucosal injury and bacterium translocation and thus tamper the recovery process. It has been well-documented that L-Arg can improve NO level and NO is supposed to protect the transplanted small bowel from mucosal injury and thus facilitate its functional recovery. As well-known necessary for cell metabolism of gut tract, Gin plays vital roles in integrity maintenance and injury repair of intestinal mucosa. This study was conducted to investigate the theraputic and synergetic effects of L-Arg and Gin in ischemia!reperfiision injure of graft. Methods: Ischemia/reperfusion injure model in rat SBT was previously established.The present study includes of two parts. In part 1,32 SD rats were randomly divided into two groups: controi(n=1 6) and SBT(n=1 6). The animals were sacrificed at 20 minutes after reperfusion and 1 day after operation. In part 2, 112 SD rats were randomly divided into 4 groups: 1), the control group(control, n=16) underwent suppositional operation; 2), SBT+standard TPN group(sTPN, n=2 X 16); 3), SBT+ Ala-Gin Dipeptiven +TPN group (dTPN, n=2 X 16); 4), SBT+L-Arg + Ala-Gin Dipeptiven +TPN group(aTPN, n=2 X 16). The rats were sacrificed 4 and 8 days postoperation to measure Gin level in serum and mucosai NO, MDA, GLN content and histological changes. Results: 1), Graft mucosal MDA increased to a significant level (P<0.01) in 4 comparison with the control immediately after blood reperfusion and began to decrease gradually thereafter. Normal level was seen 8 days in the sTPN group and dTPN group and 4 days in the aTPN group postoperation. 2), The graft mucosai NO content decreased immediately after 20 minutes of reperfiision in SBT group,and lower than control group(P<0.0l), resumed normal 1 day later. 4 and 8 days after operation, mucosal NO levels were nomal in sTPN group and dTPN group but still higher than control group in aTPN group(P拁zO.0l, P<0.O 1). 3), serum and mucosal Gin level, vilius height and mucosal thickness were all greater in dTPN group and aTPN group than in sTPN group, indicating that Ala-Gin Dipeptiven accelerated the regenerating process of graft mucosa. 4), Mucosal Gin Ievel(P<0.05) and villus height(P<0.05) were higher in aTPN group than in dTPN group at day 4 after operation but almost the same at day 8. Conclusion: 1), Ala-Gin Dipeptiven can maintain and improve serum and graft mucosal Gin level. 2), Ala-Gin Dipeptiven application during TPN can help repair graft mucosa. 3), L-Arg can improve the serum and graft mucosa NO level. 4), L-Arg is synergetic to the mucosal- recovery- stimulating activity of Ala-Gin Dipeptiven.更多还原