肿瘤坏死因子在梗阻性黄疸肝损伤中的实验研究

THE ROLE OF TNF-α IN INJURY OF RATS WITH OBSTRUCTIVE JAUNDICE

目的 研究梗阻性黄疸鼠内毒素（ＬＰＳ）血症时肝组织液中ＴＮＦ－ α活性与肝细胞损伤的关系。方法 将３２ 只大白鼠均作胆总管结扎，切断，复制梗阻性黄胆模型，随机分为三组，于术后第五天处死。ＢＤＬ＋ ＬＰＳ组于处死前１２ 小时经腹腔注射０．７５ｍ ｇ／ｋｇ 的ＬＰＳ。ＰＴＸ组术后第二天以０．５％ ＰＴＸ以１ｍ ｌ／１００ｇ管饲，一次／日，于处死前１２ 小时经腹腔注射０．７５％ ／ｋｇ的ＬＰＳ。动物处死后取心血作肝功能测定，部分肝组织作病理切片，其余大部分肝组织提取组织液。结果 血清中总胆红素三组均明显升高，以可溶性的直接胆红素为主，证实为梗阻性黄疸。ＡＬＴ，ＡＳＴ及肝组织液中ＴＮＦ活性浓度明显升高，以ＢＤＬ＋ ＬＰＳ组明显，与ＢＤＬ组和ＰＴＸ组比较，差异显著。三组肝脏肿大瘀胆，胆总管近端扩张明显，充满胆汁。ＢＤＬ＋ ＬＰＳ组肝脏肿大更加明显。光镜下示：ＢＤＬ组和ＰＴＸ组结果示鼠肝血窦扩张，胆管细胞增生伴炎性细胞浸润，肝细胞浊肿。ＢＤＬ＋ ＬＰＳ组肝血窦扩张及ＰＭＮ浸润更加明显，肝小叶结构破坏伴肝细胞片状坏死。结论 内毒素诱导产生的肝组织内活性ＴＮＦ－ α是肝细胞损伤重要因素之一，且呈正相关作用。

Objective to assess whether the increase of bioactivite TNF-α in heptic tissiue fluid and the cause of the pathology of live in billiary obstructed rat with endotoxin.Methods Thirty-two rats were operated,the commone bile duct was ligated and divided,randomly assigned to three groups,and sacrificed five day late.In BDL group,only 0.9%N.S were ingested following surgery.In BDL+LPS group,0.75% of LPS were given intraperitoneally 12h before sacrificed.In PTX group,0.5% of PTX were ingested follwing surgery,0.75% of LPS were given intraperitoneally.when the rats were sacrificed,their blood were taken to determinase total TB,DB,AST,ALT.The part of live were taken for microscopine exammation,others for extracting tissiue fluid.L929 cell cytotoxicity assay was used to deterimine the presence of bioactivite TNF-α.Result The serum TB,DB,AST,ALT in three group were significiantly increased.and the BDL PTX group:BDL+LPS group had significiantly difference(P<0.05).On microscopic examination,there were degeneration of hepatocytes and neutrophil infiltration in the liver in BDL group as well as PTX group.The changes in BDL+LPS group was more severe than in others groups and focal necrosis of hepatocytes and lobules damage were observed.THF-α bioactivitv assay:BDL gorup was 36.65～3.98 and PTX group 50.75～13.40,biological activity hepatiotissue fluid of (BDL+LPS group 105.14～18.51) had significiantly increased(P<0.001).Conclusion TNF-α induced by LPS mediated hepatic injury with obstractive jaundice can cause hepatic injury.