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1、S-腺苷蛋氨酸對(duì)內(nèi)毒素性肝損害保護(hù)作用的研究張釗，龔建平（400010重慶，重慶醫(yī)科大學(xué)第二附屬醫(yī)院肝膽外科）[摘要]目的探討S-腺苷蛋氨酸(S-adenosylmethionine,SAM)對(duì)內(nèi)毒素(1ipolmlysaccharide,LPS)性肝損害的保護(hù)機(jī)制。方法100只BABL/c小鼠隨機(jī)均分為兩組，LPS組腹腔注射10mg/kg的LPS，SAM組在注射10mg/kgLPS前2h于小鼠腹腔內(nèi)注射100mg/kg的SAM。記錄兩組小鼠存活率；光鏡和電鏡觀(guān)察組織病理學(xué)改變；酶聯(lián)免疫吸附法（ELISA
2、）檢測(cè)血清中腫瘤壞死因子-α(TNF-α)和白細(xì)胞介素-10（IL-10）的濃度；免疫組織化學(xué)法（SABC）和蛋白免疫印跡法（Westernblot）檢測(cè)肝組織中Toll樣受體4(TLR4)和肝X受體α(LXRα)的蛋白表達(dá)水平。結(jié)果S-腺苷蛋氨酸能明顯提高小鼠存活率[(50.0%、40.0%、30.0%、30.0%)對(duì)(80.0%、70.0%、60.0%、50.O%)，P＜0.05]，肝臟病理?yè)p害程度減輕；SAM組血清中TNF-α水平顯著低于LPS組，差異有統(tǒng)計(jì)學(xué)意義[(1791.79±122.19)p
3、g/ml對(duì)(718.83±53.27)pg/ml，P＜0.05]；SAM組血清中IL-10增加且高峰前移，與LPS組比較差異有統(tǒng)計(jì)學(xué)意義[(418.69±38.77)pg/ml對(duì)(347.09±31.37)pg/ml，P＜0.05]；SAM組肝組織中LXRα表達(dá)明顯增加，而TLR4表達(dá)則明顯減少，兩者與LPS組比較差異均有統(tǒng)計(jì)學(xué)意[Westernblot灰度值（TLR4：1.550±0.034對(duì)1.365±0.017，LXRα：1.605±0.027對(duì)1.375±0.014），P＜0.05]。結(jié)論SAM能
4、明顯減輕LPS所致的肝損害，其機(jī)制可能與其降低肝臟各種細(xì)胞TLR4的表達(dá)，增強(qiáng)LXRα的表達(dá)，最終導(dǎo)致TNF-α水平降低和IL-10水平增高有關(guān)。[關(guān)鍵詞]S-腺苷蛋氨酸；內(nèi)毒素；肝X受體α；Toll樣受體4[中圖法分類(lèi)號(hào)][文獻(xiàn)標(biāo)志碼]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
