谷氨酰胺对肝移植大鼠肠黏膜形态与肠黏膜免疫功能的影响

Effects of glutamine on shape and immune function of intestinal mucosa in liver transplantation rats

目的:探讨谷氨酰胺(glutamine,Gln)对原位肝移植后大鼠肠黏膜形态与肠黏膜免疫功能的影响。方法:健康雄性Wistar大鼠70只,随机分为正常对照组(n=10)、原位肝移植(orthotopic liver transplantation,OLT,n=30)组和OLT+Gln组(Gln组,n=30);正常对照组只分离肝十二指肠韧带,OLT组和Gln组按改良的两袖套法进行OLT。术前3 d、术后3 h开始Gln组受体给予肠内营养混悬液能全力+谷氨酰胺灌胃,OLT组及正常对照组受体仅给予肠内营养混悬液能全力。正常对照组于术后12 h、OLT组和Gln组于术后12、24、72 h分别取回肠肠壁组织行光镜和电镜观察肠黏膜形态及微绒毛长度测定、检测肠黏膜肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量、分泌型免疫球蛋白A(secretory immunoglobulin A,sIgA)和肠黏膜上皮内淋巴细胞增殖活力。结果:OLT组和Gln组肠黏膜损害较正常对照组明显加重,而Gln组24、72 h肠黏膜损害较OLT组明显减轻(P<0.01);OLT组和Gln组肠黏膜TNF-α含量较正常对照组明显升高,而Gln组较OLT组明显下降(P<0.01);OLT组12、24、72 h和Gln组12、24 h肠黏膜sIgA含量、肠黏膜上皮内淋巴细胞增殖活力较正常对照组明显降低,而Gln组24、72 h较OLT组含量明显升高(P<0.01)。结论:大鼠OLT可引起肠组织中TNF-α表达上调、sIgA和肠黏膜上皮内淋巴细胞增殖活力下降导致肠黏膜机械屏障和免疫屏障损伤,围手术期应用Gln能抑制肝移植大鼠肠黏膜TNF-α表达,提高sIgA含量和肠黏膜上皮内淋巴细胞增殖活力而起到肠黏膜保护作用。

Objective：To explore the effects of glutamine（Gln）on shape and immune function of intestinal mucosa in liver transplantation rats.Methods：Seventy healthy male Wistar rats were randomly divided into three groups：normal control group（control group,n= 10）,orthotopic liver transplantation group（OLT group,n=30）and OLT ＋ Gln group（Gln group,n=30）.Dissection of hepatoduodenal ligament was performed in control group and OLT by modified two-cuff method was performed in OLT group and Gln group.For Gln group,recipients were supplied with nutrison fiber（125 ml/（kg·d））plus Gln（0.3 g/（kg·d））by gastric perfusion at 3 d before surgery and at 3 h after surgery.For OLT group and control group,recipients were supplied with nutrison fiber（125 ml/（kg·d））only.Ileal intestinal wall tissues were taken at 12 h after surgery in control group and at 12,24,72 h after surgery in OLT and Gln groups.Intestinal mucosa shape was observed by light microscopy and electron microscopy,length of the microvilli was measured and intestinal mucosa tumor necrosis factor-α（TNF-α）levels,secretory immunoglobulin A（sIgA）and proliferative activities of epithelial lymphocytes in intestinal mucosa were detected.Results：Intestinal mucosal damage was more severe in OLT group and Gln group than in control group,however it was lighter in Gln group at 24 h and 72 h than in OLT group（P〈0.01）.TNF-α contents were significantly higher in OLT group and Gln group than in control group,but they were significantly lower in Gln group than in OLT group（P〈0.01）.Intestinal mucosa sIgA contents and proliferative activities of epithelial lymphocytes in intestinal mucosa were obviously decreased in OLT group at 12,24,72 h and Gln group at 12 h and 24 h than in control group,but they were significantly increased in Gln group at 24 h and 72 h than in OLT group（P〈0.01）.Conclusions：OLT can increase TNF-α expressions,decrease sIgA contents and decline proliferative activities of epithelial lymphocytes in intestinal mucosa, which will cause damages to intestinal mechanical barrier and immune barrier.Peri-operative application Gln can inhibit TNFα expressions in intestinal mucosa of rats with liver transplantation,increase sIgA contents and improve proliferative activities of epithelial lymphocytes in intestinal mucosa thus protect intestinal mucosa.