s-腺苷蛋氨酸对内毒素性肝损害保护作用的研究

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1、S-腺苷蛋氨酸对内毒素性肝损害保护作用的研究张钊，龚建平（400010重庆，重庆医科大学第二附属医院肝胆外科）[摘要]目的探讨S-腺苷蛋氨酸(S-adenosylmethionine,SAM)对内毒素(1ipolmlysaccharide,LPS)性肝损害的保护机制。方法100只BABL/c小鼠随机均分为两组，LPS组腹腔注射10mg/kg的LPS，SAM组在注射10mg/kgLPS前2h于小鼠腹腔内注射100mg/kg的SAM。记录两组小鼠存活率；光镜和电镜观察组织病理学改变；酶联免疫吸附法（ELISA

2、）检测血清中肿瘤坏死因子-α(TNF-α)和白细胞介素-10（IL-10）的浓度；免疫组织化学法（SABC）和蛋白免疫印迹法（Westernblot）检测肝组织中Toll样受体4(TLR4)和肝X受体α(LXRα)的蛋白表达水平。结果S-腺苷蛋氨酸能明显提高小鼠存活率[(50.0%、40.0%、30.0%、30.0%)对(80.0%、70.0%、60.0%、50.O%)，P＜0.05]，肝脏病理损害程度减轻；SAM组血清中TNF-α水平显著低于LPS组，差异有统计学意义[(1791.79±122.19)p

3、g/ml对(718.83±53.27)pg/ml，P＜0.05]；SAM组血清中IL-10增加且高峰前移，与LPS组比较差异有统计学意义[(418.69±38.77)pg/ml对(347.09±31.37)pg/ml，P＜0.05]；SAM组肝组织中LXRα表达明显增加，而TLR4表达则明显减少，两者与LPS组比较差异均有统计学意[Westernblot灰度值（TLR4：1.550±0.034对1.365±0.017，LXRα：1.605±0.027对1.375±0.014），P＜0.05]。结论SAM能

4、明显减轻LPS所致的肝损害，其机制可能与其降低肝脏各种细胞TLR4的表达，增强LXRα的表达，最终导致TNF-α水平降低和IL-10水平增高有关。[关键词]S-腺苷蛋氨酸；内毒素；肝X受体α；Toll样受体4[中图法分类号][文献标志码]AProtectiveeffectofS-adenosylmethionineagainstliverinjuryinducedbylipopolysaccharidesZHANGZhao,GONGJian-Ping(DepartmentofHepatobliliaryS

5、urgery,SecondAffiliatedHospital,ChongqingUniversityofMedicalSciences,Chongqing400010,China)[Abstract]ObjectiveTostudytheprotectivemechanismofS-adenosylmethionine(SAM)underlyingliverinjuryinducedbylipopolysaccharides(LPS).MethodsOnehundredBABL/cmicewereran

6、domlydividedintoLPSgroupandSAMgroup.MiceinLPSgroupwereintraperitoneallyinjectedwith10mg/kgLPS,miceinSAMgroupwereinjectedwith100mg/kgSAM2hbeforereceivingthesamedoseofLPS.Thesurvivalrateofmiceintwogroupswasrecorded.Histopathologicalchangesinliverofmiceweree

7、xamined.Tumornecrosisfactor-α(TNF-α)andinterleukin-10(IL-10)levelsinserumweremeasuredbyELISAanalysis.Expressionoftolllikereceptor4(TLR4)andliverXreceptorα(LXRα)inhepatictissueswasdetectedbyimmunohistochemistryandWesternblot.ResultsSAMincreasedthesurvivalr

8、ateofmicefrom50.0%,40.0%,30.0%,and30.0%beforeitsinjectionto80.0%,70.0%,60.0%,and50.0%afteritsinjection(P＜0.05),andattenuatedtheLPS-inducedpathologicchangesinlivertissue.TheserumTNF-αlevelwassignificantlylowerinSAMgr