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肠梗阻导致肠功能不全的中西医结合实验研究

Experimental Study of Integrated Traditional Chinese and Western Medicine on Intestinal Dysfunction by Intestinal Obstruction

【作者】 李琳

【导师】 周振理; 殷铭;

【作者基本信息】 天津医科大学 , 中西医结合临床, 2008, 博士

【摘要】 目的:利用可复性机械性完全性肠梗阻模型,观察肠梗阻对于肠屏障功能、营养状况及免疫功能的影响。观察肠梗阻梗阻解除后自然恢复及中药四君子汤对肠屏障功能、营养状况及免疫功能的影响。方法:对动物模型梗阻1天、2天、3天时内毒素、肠粘膜损伤评分、小肠上皮层粘膜完整性情况,总蛋白、白蛋白、前白蛋白、肌酐、转铁蛋白、胰岛素样生长因子-1,白介素-2、肿瘤坏死因子-α、免疫球蛋白IgG、IgM、IgA、补体C3、C4、T淋巴细胞亚群(CD4+、CD8+、CD4+/CD8+)情况分别进行检测和观察。同时观察肠梗阻解除后,应用四君子汤对上述指标的影响。结果:本实验显示梗阻后模型动物血浆内毒素水平以及Chiu肠粘膜损伤评分明显高于正常对照组。而梗阻后模型动物肠粘膜厚度、肠绒毛高度、隐窝深度、绒毛表面积明显低于正常对照组。血浆内毒素与Chiu肠粘膜损伤评分有明显正相关,而与小肠上皮层绒毛表面积有明显负相关。总蛋白、白蛋白、前白蛋白、肌酐、转铁蛋白、胰岛素样生长因子-1测定均有所下降,以前白蛋白、转铁蛋白、胰岛素样生长因子-1较为敏感,前白蛋白、转铁蛋白、胰岛素样生长因子-1三者有正相关性。肠梗阻后1天工L-2便开始明显下降,肿瘤坏死因子-α在梗阻后2天明显升高,免疫球蛋白IgG、IgM、IgA、补体C3、C4梗阻后1天已明显升高,而后逐渐上升,CD4+T细胞百分比、CD4+/CD8+比值在肠梗阻后开始上升,梗阻后2天明显高于正常对照组,同时CD8+T细胞百分比明显低于正常对照组;梗阻后3天CD4+T细胞百分比和CD4+/CD8+比值明显低于正常对照组,CD8+T细胞百分比则明显高于正常对照组。在肠梗阻解除后,内毒素水平逐渐降低,且中药治疗组血浆内毒素水平以及Chiu肠粘膜损伤评分明显低于自然恢复组,中药治疗组绒毛表面积明显高于自然恢复组。总蛋白有所下降,白蛋白变化不明显,转铁蛋白、前白蛋白、胰岛素样生长因子-1均有所上升,而中药治疗组明显高于自然恢复组。肠梗阻解除后2天、4天白介素-2升高,中药治疗组明显高于自然恢复组,肿瘤坏死因子-α降低,而中药治疗组明显低于自然恢复组;免疫球蛋白IgG、IgM、IgA,补体C3、C4在梗阻解除后明显下降,而中药治疗组明显高于自然恢复组;CD4+T细胞百分比、CD4+/CD8+比值在肠梗阻解除后不断下降,而中药治疗组明显高于自然恢复组。结论:肠梗阻后血浆内毒素水平不断升高,肠粘膜损伤不断加重,导致肠粘膜屏障破坏不断加重。由于摄入吸收不足及机体的应激状态,导致蛋白质营养不良。在肠梗阻早期,由于肠屏障破坏及肠功能不全,使肠道细菌及内毒素发生移位等,刺激机体的免疫系统,使机体多种免疫机制增强。随着梗阻时间的延长,免疫系统受到破坏,全身免疫功能出现障碍。肠梗阻解除后,中药四君子汤可有效地修复损伤的肠粘膜上皮细胞,具有保护肠粘膜屏障的功能。同时表现为营养不良和脾胃虚弱,应用中药四君子汤可调节肠道运动和消化吸收功能,增强肠道适应性,改善脾胃虚弱,加快恢复机体的营养代谢和营养状况。而且机体免疫力低下,中药四君子汤益气健脾,促进脾的运化,增进气血,改善机体各种虚损状况,从而纠正免疫紊乱。

【Abstract】 Objective:The changes of intestinal mucosal barrier, nutritional status, immunologic function in intestinal obstruction rabbit model were investigated. And the effects of early application of Sijunzi Decoction on intestinal mucosal barrier, nutritional status, immunologic function after relieving obstruction was assessed.Method:After intestinal obstruction was made, the serum endotoxin, histopathological evaluation scores, the integrality of intestinal epithelium,levels of TP,ALB,Cr,PALB,TRF, IGF-1, IL-2/TNF-α, IgG, IgM, IgA, C3, C4 and T lymphocyte subsets were measured or observed by microscope in 24,48,72 hours. After relieving obstruction,the index above all were measured and was observed by microscope in 48,96 hours.Result:The serum endotoxin and Chiu’s histopathological evaluation score were higher obviously in intestinal obstruction model groups than those in control group. The thickness of intestinal mucosa,the height of villus,the depth of recess and the surface area of villus were lower obviously. The levels of endotoxin and Chiu’s histopathological evaluation score were significantlly positive correlated. Moreover,it and the surface area of villus were significantlly negative correlated. Levels of TP,ALB,Cr,PALB,TRF and IGF-1 were lower gradually.Especially PALB,TRF and IGF-1 were sensitive comparatively. Levels of PALB,TRF and IGF-1 were significantlly positive correlated. Levels of IL-2 was obviously lower. Levels of TNF-a,IgG,IgM,IgA,the percentum CD4+T cell and the ratio CD4+/CD8+were obviously higher after intestinal obstruction. Nevertheless,in intestinal obstrution 72 hours the percentum CD4+T cell and the ratio CD4+/CD8+ were obviously lower than in control group. The level of endotoxin and Chiu’s histopathological evaluation score were obviously lower in the Sijunzi Decoction groups than in the natural recovery groups.The surface area of villus was obviously higher in the Sijunzi Decoction groups.Levels of TP,ALB, PALB,TRF and IGF-1 were obviously higher. The level of IL-2, IgG, IgM, IgA, C3 and C4,the percentum CD4+T cell and the ratio CD4+/CD8+were obviously higher in the Sijunzi Decoction groups. Moreover,the level of TNF-αwas obviously lower. Conclusion:The intestinal mucosal barrier was seriously destroyed after intestinal obstruction.The body was on negative nitrogen equilibrium to bring on protein malnutrition.The breakage of gut barrier, enterogenous bacteria and endotoxin translocation etc. activated immunologic system in the early intestinal obstruction. Concomitantly the intestinal was obstructed, immunologic system was destroyed. The Sijunzi Decoction can protect intestinal mucosal barrier function and regulate the movement and digest and absorption functions of intestinal tract to strengthen adaptability of intestinal tract and to improve spleen and stomach deficiency.And it can correct the disorder of immunologic system and improve immunologic function.

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