【作者】 郭峰；

【导师】 何建平； 李继梅； 杨福；

【作者基本信息】 昆明医学院 ， 外科学， 2009， 硕士

【摘要】 【目的】观察大鼠急性肝衰竭时肠粘膜屏障功能损害及甲状腺激素代谢异常,探讨补充外源性甲状腺激素对损害肠粘膜屏障的影响。【方法】SD大鼠34只,随机分为三组:①正常对照组（SO组）10只②急性肝衰竭组（AHF组）12只。③急性肝衰加甲状腺激素治疗组（AHF+TH组）12只。后两组大鼠按400mg/kg的标准腹腔内注射硫代乙酰胺（TAA）,24h后用相同剂量TAA重复注射1次,模拟建立大鼠急性肝衰竭模型。AHF+TH组大鼠于造模前30min、首次腹腔注射TAA后18h、36h,分别按15μg·kg^-1的标准腹腔注射甲状腺激素,共三次。各组大鼠于腹腔初次注射TAA始48h宰杀,取下腔静脉血检测FT₃、FT₄、TSH、rT₃及TB、ALT、AST等肝功能指标,取门静脉血测内毒素水平,取小肠组织测二胺氧化酶（DAO）活性,取小肠内容物及肠系膜淋巴结行细菌培养,取肝脏及末段回肠行普通HE染色观察,并使用图像分析系统测量小肠绒毛长度并行末段回肠壁内细胞间粘附因子I（ICAM-1）定量检测。【结果】1.与SO组比较,AHF组、AHF+TH组FT₃、FT₄降低（p＜0.01）,rT₃升高（p＜0.01）,TB、ALT、AST水平上升（p＜0.01）,门静脉血浆内毒素水平显著升高（p＜0.01）,小肠组织DAO活性下降（p＜0.01）,小肠绒毛长度下降（p＜0.01）,肠粘膜损伤评分增高（p＜0.01）,小肠组织ICAM-1的表达水平升高（p＜0.01）,肠系膜淋巴结细菌移位率增大（p＜0.01）。大鼠肠道4种正常菌数量均发生了显著性变化,其中肠杆菌、肠球菌数量明显上升（p＜0.01）,双歧杆菌、乳酸杆菌数量显著下降（p＜0.01）,出现肠道菌群失调。2.AHF+TH组与AHF组比较,外周血FT₄升高（p＜0.01）,FT₃升高（P＜0.05）,rT₃降低（p＜0.01）,ALT、AST、TB水平下降（p＜0.05）,门静脉血浆内毒素水平降低（p＞0.05）,小肠组织DAO活性升高（p＜0.05）,小肠绒毛长度升高（p＜0.05）,肠粘膜损伤程度降低（p＜0.05）,肠系膜淋巴结细菌移位率及小肠组织ICAM-1的表达水平有所下降但无统计学意义（p＞0.05）。肠道各菌种变化较AHF组缓和,其中乳酸杆菌虽升高但无显著差异（p＞0.05）,双歧杆菌有所升高（P＜0.05）,肠杆菌、肠球菌下降（P＜0.05）。【结论】急性肝衰竭时发生肠粘膜屏障的损害,且存在甲状腺激素代谢异常:FT₃、FT₄降低,rT₃升高。同时存在小肠组织二胺氧化酶（DAO）活性下降、门静脉血清内毒素水平升高、细菌移位等。补充外源性甲状腺激素有一定的保护肝脏功能和保护肠粘膜屏障的作用。更多还原

【Abstract】 Objective:To investigate the injury of intestinal mucosa barrier,the metabolic abnormalities of thyroid hormone（TH）,and the protective effect of exogenous thyroid hormone（TH） on intestinal mucosa barrier in rats with acute hepatic failure.Methods:Thirty-four SD rats were randomly divided into three groups:ⅠSham group（SO group）,N=10;ⅡAcute hepatic failure group（AHF group）, N=12;ⅢAHF treated with thyroid hormone（AHF+TH group）,N=12.The AHF Rat model（ⅡandⅢgroups） was created by repeated treatment of thioacetamide（TAA）, 400mg/kg body weight（saline preparation 40mg/ml）,by intraperitoneal injections at 0 and 24 hours.The rats in groupⅢ（AHF+TH group） were treated with three intraperitoneal thyroid hormome（TH） injections（15mg/kg） at-30 min,18 hours and 36 hours post TAA treaements.All rats were slaughtered at 48 hours after the initial TAA intraperitoneal injection,and underwent serum FT₃,FT₄,TSH,rT₃,endotoxin, TB,and ALT level measurements.The levels of diamine oxidase（DAO） and ICAM-1 expression in the intestine were measured.The bacteria in ileum and mesenteric lymph nodes were also cultured to observe the structural integrity of the intestinal mucosa.Results:1) GroupⅡ（AHF group） andⅢ（AHF+TH） were compared to the Sham group respectively.We found that the serum levels of FT₃,FT₄ and the activities of DAO were decreased（p＜0.01）,whereas the serum levels of rT₃,TB,AST,ALT,endotoxin and ICAM-1 expressions in the intestine were increased（p＜0.01）.The migration of Enterobacteriaceae and enterococci to the mesenteric lymph nodes were increased （p＜0.01）.In contrast,the migration of lactobacillus and bifidobacteria to the same location were decreased（p＜0.01）.As a result,this disrupted the balance of bacterial composition in the intestine.2) When groupⅢ（AHF+TH group） was compared to groupⅡ（AHF）,we found that the serum level of FT₃,FT₄ and the activities of DAO in the intestine were increased（p＜0.01/0.05） after thyroid hormone treatment in groupⅢ.In contrast,the serum level of rT₃,TB,ALT,AST were decreased（p＜0.01/0.05）.The number of intestinal Enterobacteriaceae and enterococci were decreased（p＜0.05）,whereas the number of lactobacillus and bifidobacteria were increased in the intestine.And the migration rate of bacteria to the mesenteric lymph nodes,endotoxin and ICAM-1 expressions in the intestine were decreased,although not significantly（p＞0.05）. This showed the injury of intestinal mucosa barrier was lessened（p＜0.05）Conclusion:Follow with the injure of intestinal mucosa barrier of acute hepatic failure,the level of FT₃,FT₄ and the activities of diamine oxidase were degraded,and the level of rT₃,the shifting rate of bacterium,endotoxin were increased.The supplement of exogenous thyroid hormone（TH） can protect intestinal mucosa barrier and the function of liver,and alleviate the injure of intestinal mucosa barrier in rats with acute hepatic failure.更多还原