TLR4在华支睾吸虫感染致小鼠肝纤维化作用的研究

目的探讨TLR4基因在华支睾吸虫感染小鼠致肝纤维化中的作用。方法建立感染华支睾吸虫C3H/HeN(TLR4野生型)与C3H/HeJ(TLR4基因突变型)小鼠模型,在感染后1d、7d、2W、4W、8W、12W取小鼠肝脏,切片并进行HE和Masson染色,观察病理变化。结果 C3H/HeN小鼠肝脏大体病变从2W开始,随感染时间延长而加重;C3H/HeJ小鼠从2W开始,4W加重,至8W已明显减轻。观察HE、Masson染色肝脏切片示随感染时间的延长,C3H/HeN小鼠前期肝纤维化逐渐加重,至8W起趋于稳定;2W~12W纤维化评分均高于感染前(P0.01)。C3H/HeJ小鼠肝纤维化评分2W升高,4W达高峰并显著高于感染前(P0.01),至8W明显下降。与C3H/HeN比较,感染后2W、4W、8W、12W C3H/HeJ小鼠肝纤维化程度轻(P0.01)。感染后7d,C3H/HeN小鼠的HE染色切片上可见嗜酸性粒细胞,4W达高峰,此后明显减少。感染后2W、4W、8W,C3H/HeJ小鼠嗜酸性粒细胞较C3H/HeN小鼠少(P0.05)。结论 TLR4基因缺失可能在华支睾吸虫感染致肝纤维化过程起一定的阻制作用,从而减缓肝纤维化的进程。     

克雷伯氏肺炎杆菌内毒素诱导小鼠β—防御素—4基因表达及其信号传递

目的 探讨用克雷伯氏肺炎杆菌内毒素（LPS）对小鼠β－防御素表达的影响及其相关的信号传导通路。方法 分别给予C3H／HeJ和C3H／HeN小鼠腹腔注射LPS（4mg/kg),于不同时间点采取气管、肺、肾管组织,提取总RNA。用RT－PCR检测各组织β-防御素－3和／或β-防御素－4mRNA的表达,并对扩增出的cDNA片段进行测序;同步用Western blot法检测该两系小鼠肺脏1－kBa磷酸化情况（p-I-kBa)和I－kBa的量。结果 （1）经LPS处理24小时后的C3H／HeN小鼠,其肺脏表达β-防御素－4mRNA而C3H／HeJ小鼠未见表达。（2）与未给予LPS处理小鼠比较,经LPS处理4小时后,C3H／HeN小鼠肺组织p-kBa含量明显增高;LPS处理后8小时,p-I-kBa以及I-kBa含量均呈减少趋势;至第24小时,p-I-kBa和I－kBa含量均明显减少。而C3H／HeJ小鼠肺组织p-I-kBa及I－kBa含量均未见相应变化。结论 克雷伯氏肺炎杆菌内毒素能诱导C3H／HeN小鼠肺β-防御素－4的表达,其诱导表达作用与Toll受体蛋白－4介导的NF－kB活化级联信号传递通路有关。     

EHEC：O157感染后小鼠肾细胞凋亡的检测

目的 检测C3H/HeJ和C3H/SW小鼠感染肠出血性大肠杆菌(EHEC:O157)后肾细胞凋亡,并探讨thl4基因突变对肾细胞凋亡的影响.方法 流式细胞术(FCM)检测C3H/HeJ和C3H/SW小鼠感染EHEC:O157后肾细胞凋亡率,采用SPSS11.0统计软件分析结果.结果 C3H/HeJ小鼠肾细胞凋亡率明显高于C3H/SW小鼠,差异有统计学意义(P<0.05).结论 小鼠感染EHEC:O157后肾细胞凋亡与thl4基因突变相关.     

Impact of Toll-like Receptor 4 Deficiency on Cerebrocardiac Syndrome

In order to investigate the role of Toll-like receptor 4 （TLR4） in cerebrocardiac syndrome （CCS）, the partial cerebral ischemia/reperfusion （I/R） models in mice with different TLR4 genotypes were established in the present study. TLR4 wild-type （C3H/HeN） and mutant （C3H/HeJ） mice of 6-8 weeks of age were divided into 4 groups at random： C3H/HeN sham group （n=10）, C3H/HeJ sham group （n=10）, C3H/HeN model group （n=10） and C3H/HeJ model group （n=10）. Partial cerebral I/R was caused by the middle cerebral artery occlusion （MCAO） to duplicate CCS models in mice. After the operation, the electrocardiogram （ECG）, the level of tumor necrosis factor-alpha （TNF-c0 in myocardial tissue and the cardiac pathological changes were observed in each group. It was shown that the brain infarct volume in C3H/HeN model group was larger than that in C3H/HeJ model group （P〈0.01）. The ST segment change and T wave inversion occurred frequently in model groups. Moreover, the TNF-ct level in C3H/HeN model group was higher than that in C3H/HeJ model group （P〈0.01）. The myocar- dial injury was aggravated in C3H/HeN group as compared with C3H/HeJ group. It was concluded that TLR4 was implicated in the development of CCS.     

脂多糖诱导下急性肾功能衰竭小鼠肾脏中TOLL样受体4的表达

目的:探讨TOLL样受体4(TLR4)在脂多糖(LPS)诱导的小鼠急性肾功能衰竭(ARF)肾脏中表达及意义。方法:建立LPS诱导的小鼠ARF模型。应用免疫组织化学SABC法、Western blot及RT-PCR法检测肾组织TLR4蛋白及mRNA的表达变化。TUNEL法检测肾脏的凋亡情况。结果:TLR4在正常组(NG)肾脏中主要分布于肾小管、管周、肾间质区,肾小球系膜区也有表达,而ARF组TLR4在上述区域的表达显著增加,以近端小管、肾间质、远端小管、肾血管等部位较明显,两组光密度值比较有明显差异(P<0.05);TLR4的表达与肾功能的改变呈正相关(r=0.91);与NG组相比,ARF组的TLR4蛋白及mRNA水平的表达显著上调,以造模24 h后最明显;TUNEL法显示凋亡小体主要出现在ARF组肾脏的近端小管及管周围,肾小球无明显变化。结论:TLR4在脂多糖诱导的小鼠ARF肾脏中有较高表达,同时在其肾近端小管及小管周围组织发现较明显的凋亡小体。二者在ARF发病中可能起重要作用。     

姜黄素抑制内毒素所致小鼠急性肾功能损害的作用

目的探讨姜黄素对内毒素(LPS)诱导小鼠急性肾损害的保护效应.方法通过小鼠腹腔注射LPS复制脓毒症模型.将52只小鼠分为正常对照组(n=12)、LPS组(n=20 )和治疗组(LPS 姜黄素)(n=20只),致伤后3、6、12、24 h取材,检测肾组织TLR2 mRNA表达、TNF-α水平和血清尿素氮(BUN)、肌酐(Cr)水平,同时观察肾脏病理组织学改变.结果 LPS组TNF-α水平于各时相点均显著高于对照组,6 h达峰值,同时伴随血清Cr、BUN水平升高,其变化趋势与TNF-α相一致.TLR2 mRNA表达也于LPS注射后3 h明显增加,6 h达峰值,且持续增高至24 h.而肾组织的病理改变主要表现为肾小管的坏死、脱落,管型形成,肾小球缺血、皱缩,肾组织内见多量PMN滞留.与LPS组相比较,姜黄素治疗组TLR2 mRNA表达、TNF-α水平和Cr、BUN水平于3、6、12 h明显下降,肾组织的病理损害程度较LPS组明显减轻,主要表现为肾小球无明显缺血改变和PMN滞留减少.结论早期给予姜黄素治疗,能明显改善LPS诱导的急性肾损害,并对其功能具有良好的保护效应.     

脂多糖促进人近端肾小管上皮细胞TLR4的表达

目的:研究人近端肾小管上皮细胞(HKC)在脂多糖(LPS)刺激下Toll样受体4(TLR4)的表达及作用。方法:实验细胞分两组,LPS刺激组(50mg/LLPS加入体外培养的HKC)和正常对照组;应用免疫荧光染色在激光共聚焦显微镜下观察LPS刺激24h后TLR4在HKC中的分布及表达强弱;半定量RT-PCR和免疫蛋白印迹检测各组TLR4及内参照β-actin在mRNA水平和蛋白水平的表达量;Annexin V-FITC结合流式细胞仪检测各组细胞的早期凋亡率情况。结果:LPS刺激组TLR4的免疫荧光强度显著高于正常对照组,TLR4主要分布于HKC的胞膜及胞质区;刺激组TLR4 mRNA表达高于正常对照组(1.051±0.082比0.38±0.036),差异有显著性(P<0.01);刺激组TLR4蛋白表达高于正常对照组(0.371±0.033比0.105±0.008),差异有显著性(P<0.01);LPS刺激组细胞的早期凋亡率(41.29%)显著高于正常对照组(2.36%)。结论:LPS能刺激HKC高表达TLR4,且促进HKC的早期凋亡,TLR4可能在LPS诱导的HKC凋亡中发挥一定的作用。     

脂多糖通过上调热休克蛋白27的表达减轻小鼠肾缺血再灌注损伤

目的 探讨热休克蛋白27 (heat shock protein-27,HSP27)在脂多糖(lipopolysaccharide,LPS)减轻小鼠肾缺血再灌注(ischemia-reperfusion,IR)损伤中的作用.方法 雄性C57BL/6小鼠随机分为4组:假手术组、LPS+假手术组、肾IR组和LPS+肾IR组,每组又分为槲皮素(quercetin,200mg/kg)亚组和溶剂对照亚组.采用右肾切除+左肾肾蒂夹闭25 min后再灌注建立肾IR模型,在肾IR前3d腹腔注射LPS(3mg/kg)进行预处理,采用槲皮素(200 mg/kg)灌胃抑制HSP27的表达.再灌注后24 h,各组小鼠经腹主动脉采血检测血清肌酐(Cr)、尿素氮(BUN)水平评估肾IR损伤模型,取左肾评估炎症反应程度、HSP27蛋白表达水平及凋亡相关蛋白easpase-3的活性.结果 LPS预处理可明显降低肾IR后的血清Cr、BUN水平,并减少肾小管损伤程度,同时能提高肾内HSP27的表达水平(P＜0.05);槲皮素能明显抑制肾内HSP27的表达水平,且能明显削弱LPS预处理对肾脏IR的减轻作用,包括升高Cr、BUN水平和造成更严重的炎症反应(P＜0.05).另外,LPS能明显降低肾脏IR后肾内caspase-3的活性,但槲皮素能明显削弱这种作用(P＜0.05).结论 LPS通过上调HSP27的表达减轻小鼠肾脏IR损伤.     

丹参酮IIA通过抑制RIP3/FUNDC1信号通路减轻LPS诱导的小鼠肾小管上皮细胞凋亡

目的 探讨丹参酮IIA在防治脓毒血症急性肾损伤（AKI）方面的作用及潜在机制。方法 将30只C57BL/6小鼠随机分为对照组（10 mg/kg LPS等体积无菌生理盐水）、LPS组（10 mg/kg LPS作用24 h）、LPS+丹参酮IIA组（10 mg/kg 丹参酮IIA预处理15 min再给予10 mg/kg LPS作用24 h）（10只/组）。给药后检测小鼠血肌酐(Scr)、血尿素氮水平(BUN),PAS染色观察小鼠肾组织病理变化,Western blot检测小鼠肾组织RIP3、Cleaved-caspase3、p18-FUNDC1表达水平。将体外培养正常的人肾小管上皮细胞（HK-2）分为空白对照组、LPS 刺激组（LPS,10 μg/mL）、LPS+siNC 组（LPS 10 μg/mL+50 nmol/L siNC）、LPS+siRIP3 组（LPS 10 μg/mL+50 nmol/L siRIP3）、丹参酮IIA干预组（LPS 10 μg/mL+ 丹参酮IIA 10 mg/L）,分别给予以上干预措施。采用TUNEL方法检测各组HK-2细胞的凋亡情况,Western blot检测各组RIP3、Cleaved-caspase3、p18-FUNDC1表达水平,qT-PCR检测RIP3基因表达水平。结果 与对照组相比,LPS作用小鼠24 h后,小鼠Scr及血BUN水平升高,PAS染色提示近段肾小管损伤,肾组织中RIP3、Cleaved-caspase3、p18-FUNDC1蛋白表达上调（P<0.001）。与LPS组相比,丹参酮IIA预处理后,小鼠Scr及BUN水平下降,PAS染色显示近段肾小管损伤减轻,肾组织中RIP3、Cleaved-caspase3、p18- FUNDC1蛋白表达下降（P<0.001）。体外研究显示,与对照组相比,LPS刺激的HK-2细胞后,TUNEL染色显示细胞凋亡水平明显增加,Cleaved-caspase3、RIP3、p18-FUNDC1表达上调（P<0.05）。应用丹参酮IIA预处理或体外沉默RIP3表达后再次予以LPS刺激细胞,TUNEL染色显示细胞凋亡水平较LPS组明显减少,Cleaved-caspase3、RIP3、p18-FUNDC1表达水平较LPS组下降（P<0.05）。结论 丹参酮IIA可能通过抑制RIP3/ FUNDC1信号通路来改善LPS诱导的肾小管上皮细胞凋亡。     

紫檀芪通过激活线粒体自噬减轻小鼠肾缺血再灌注损伤

目的 研究紫檀芪(PTE)对小鼠肾缺血再灌注损伤(IRI)的保护作用及相关机制。方法 将24只C57小鼠分成4组(n=6),包括假手术组(S组)、肾缺血再灌注组(IR组)、肾缺血再灌注+5 mg/kg PTE组(IR+PTE1组)和肾缺血再灌注+10 mg/kg PTE组(IR+PTE2组)。采用苏木素-伊红(HE)及TUNEL染色评估肾组织损伤。采用相关试剂盒检测血清肌酐(Cr)、尿素氮(BUN)、丙二醛(MDA)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6水平。采用Western blot检测肾脏组织Bcl-2相互作用蛋白3(BNIP3)和微管相关蛋白轻链(LC)-3Ⅱ的表达。结果 与S组比较,IR组血清Cr、BUN、MDA、TNF-α、IL-1β、IL-6水平升高,肾小管损伤评分及凋亡指数升高,BNIP3和LC3-Ⅱ表达下调,差异有统计学意义(P<0.05);与IR组比较,IR+PTE1组血清Cr、BUN、MDA、TNF-α、IL-1β、IL-6水平降低,肾小管损伤评分及凋亡指数降低,BNIP3和LC3-Ⅱ表达上调,差异有统计学意义(P<0.05)...     

Improved Survival and Neurological Outcomes after Cardiopulmonary Resuscitation in Toll-like Receptor 4-mutant Mice

Background:

Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system and noninfectious immune responses. It has been reported that TLR4 participates in the pathological course of ischemia/reperfusion (I/R) injury. However, the role of TLR4 in the process of I/R injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is still unknown. In this study, we investigated the effects of TLR4 mutation on survival and neurological outcome in a mouse model of CA/CPR.

Methods:

A model of potassium-induced CA was performed on TLR4-mutant mice (C3H/HeJ) and wild-type mice (C3H/HeN). After 3 min of untreated CA, resuscitation was attempted with chest compression, ventilation, and intravenous epinephrine. Behavioral tests were performed on mice on day 3 after CPR. The morphological changes in hippocampal neurons were assessed by light and electron microscopy. Expressions of TLR4 and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blot. Levels of tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were measured with enzyme-linked immunosorbent assay (ELISA).

Results:

On day 3 after resuscitation the overall mortality was 33.33% in C3H/HeJ group compared with 53.33% in C3H/HeN group (P < 0.05). And there was much higher central tendency in C3H/HeJ group than C3H/HeN group during open field test (P < 0.05). Meanwhile, the percentage of nonviable neurons was 21.16% in C3H/HeJ group compared with 53.11% in C3H/HeN group (P < 0.05). And there were significantly lower levels of hippocampal TNF-α and MPO in C3H/HeJ mice (TNF-α: 6.85±1.19 ng/mL, MPO: 0.33±0.11 U/g) than C3H/HeN mice (TNF-α: 11.36±2.12 ng/mL, MPO: 0.54±0.17 U/g) (all P < 0.01). CPR also significantly increased the expressions of TLR4 and ICAM-1 in C3H/HeN group. However, the expression of ICAM-1 was much lower in C3H/HeJ group than in C3H/HeN group after CPR (P < 0.01).

Conclusion:

TLR4 signaling is involved in brain damage and in inflammation triggered by CA/CPR.     

克雷伯氏肺炎杆菌内毒素诱导小鼠β-防御素-4基因表达及其信号传递

目的　探讨用克雷伯氏肺炎杆菌内毒素 (L PS)对小鼠 β-防御素表达的影响及其相关的信号传导通路。方法　分别给予 C3H /He J和 C3H /He N小鼠腹腔注射 L PS (4mg/kg) ,于不同时间点采取气管、肺、肾等组织 ,提取总 RNA。用 RT- PCR检测各组织β-防御素 - 3和 /或β-防御素 - 4m RNA的表达 ,并对扩增出的 c DNA片段进行测序 ;同步用 Western blot法检测该两系小鼠肺脏 I-κBα磷酸化情况 (p- I-κBα)和 I-κBα的含量。结果　 1经L PS处理 2 4小时后的 C3H/He N小鼠 ,其肺脏表达 β-防御素 - 4m RNA 而 C3H/He J小鼠未见表达 ;2与未给予L PS处理小鼠比较 ,经 L PS处理 4小时后 ,C3H/He N小鼠肺组织 p- I- κBα含量明显增高 ;L PS处理后 8小时 ,p- I-κBα以及 I- κBα含量均呈减少趋势 ;至第 2 4小时 ,p- I- κBα和 I- κBα含量均明显减少。而 C3H/He J小鼠肺组织 p- I-κBα及 I- κBα含量均未见相应变化。结论　克雷伯氏肺炎杆菌内毒素能诱导 C3H/He N小鼠肺 β-防御素 - 4的表达 ;其诱导表达作用与 Toll受体蛋白 - 4介导的 NF-κB活化级联信号传递通路有关     

TOLL样受体4对肺炎衣原体感染小鼠肺组织炎性递质的影响

目的:通过应用肺炎衣原体(Cpn)分别感染Toll样受体4(TLR4)基因突变型(C3H/HeJ品系,TLR4-/-)小鼠和野生型(C3H/HeN品系,TLR4+/+)小鼠,探讨TLR4在Cpn感染后炎性反应中的作用. 方法:TLR4突变型和野生型小鼠各60只分为4组(突变型对照组、突变型感染组、野生型对照组和野生型感染组),每组30只,随机分为5个时间点(即第1d、第4d、第7d、第14d和第21d).两感染组经鼻腔接种Cpn,两对照组则经鼻腔吸入二磷酸蔗糖(2SP)缓冲液,在上述预定时间点处死动物,采用ELISA检测肺组织肿瘤坏死因子α(TNF-α)和白细胞介素(IL)-10的含量,并行病理观察,测定肺湿质量/干质量比值(W/D). 结果:小鼠接种Cpn后,肺组织病理早期以中性粒细胞浸润、后期则以淋巴细胞浸润为主,且有肺泡间隔增宽、肺泡水肿和出血等炎性改变,炎症第21d趋于吸收.突变型感染组TNF-α的含量自第1d开始升高,第4d达峰值,随后呈下降趋势,至第21d仍高于正常,第7d、14d和21d含量分别为(1.10±0.12)、(0.72±0.12)和(0.52±0.10)pg/mg,低于野生型感染组的(1.30±0.16)、(1.01±0.19)和(0.71±0.08)pg/mg.突变型感染组IL-10的含量第4d开始升高,第7d达峰值,随后呈下降趋势,至第21d仍高于正常.第14d和第21d的含量分别为(1.08±0.08)和(0.64±0.10)pg/mg,低于野生型感染组的(1.34±0.10)和(0.79±0.05)pg/mg.突变型感染组的W/D值(3.00±0.28)在第21d高于野生型感染组(2.72±0.16). 结论: TLR4在感染后期至少部分参与Cpn感染小鼠的肺组织炎性递质生成.     

外源性一氧化碳释放分子3抑制肾脏固有树突状细胞活化的作用机制

目的：观察外源性一氧化碳释放分子3（Carbon Monoxide-releasing molecules,CORM-3, CO RM-3）对肾固有树突状细胞(Renal Dendritic Cell,rDC)生长的影响,并探讨其可能的作用机制。方法：采用C57BL/6J,TLR4-/-及TLR4+/+小鼠,制备肾脏单细胞悬液,磁珠分选CD11c + rDC,流式细胞术鉴定rDC纯度。CORM-3处理新鲜分离的rDC,ELISA检测rDC培养液上清中TNF-α蛋白水平;RT-PCR检测TLR4及TNF-α基因表达。另外建立小鼠肾脏热缺血30min + 冷保存24h模型,在冷保存期间经CORM-3处理之后分选rDC,抽提RNA,行RT-PCR检测TNF-α表达。结果：CORM-3明显抑制小鼠未成熟rDC的TLR4表达,下调作用呈剂量相关性。相较于无活性的iCORM (inactive CO-releasing molecules),CORM-3抑制LPS刺激后的rDC表达TNF-α。当TLR4缺陷之后,CORM-3不再抑制rDC 表达TNF-α。结论：CORM-3可显著抑制肾脏未成熟rDC 表达TLR4,也抑制LPS刺激和缺血损伤时炎症因子的表达,但对于TLR4缺陷小鼠这一抑制作用消失,提示CORM-3对内源性配体介导的rDC活化过程的抑制作用是由TLR4信号通路介导。     

窒息新生儿肾功能损害相关指标变化

目的 研究窒息新生儿肾功能损害相关指标的变化情况.方法 选择河南省郑州市第一人民医院2013年4月至2015年4月收治的80例窒息新生儿为研究对象,并作为窒息组.其中,轻度窒息50例,重度窒息30例;选择同期40例正常新生儿为对照组.通过全自动生化分析仪、颗粒增强透射免疫比浊法分别测定各组新生儿血肌酐(Cr)、尿素氮(BUN)及血清胱抑素C (CysC)水平,并用Pearson分析CysC与BUN及Cr的相关性.结果 窒息组BUN、Cr、CysC水平分别为(7.52±2.04) mmol/L、(113.61 ±29.65) μmol/L、(4.23 ±0.71)mg/L,高于对照组的(3.91±1.20)mmol/L、(59.63±15.60) μmol/L、(2.54±0.40) mg/L,差异均具有统计学意义(P＜0.05).轻度窒息组CysC、BUN异常率分别为74.0％、42.0％,低于重度窒息组的96.7％、66.7％,差异有统计学意义(P＜0.05).CysC与血Cr、BUN呈正相关(r=0.670、0.654,P＜0.05).结论 血清BUN、Cr及CysC,特别是CysC水平,对于判断窒息新生儿肾功能损害有重要意义.     

慢性肾功能衰竭患者尿液NAG变化的临床评价

目的 :对慢性肾功能衰竭 (CRF)患者尿液N 乙酰 B D 氨基葡萄糖苷酶 (NAG)的变化作临床研究。方法 :采用基质为对硝基苯 N 乙酰 β D 氨基葡萄糖苷酶 (PNP -NAG)的化学显色法对CRF患者及健康对照人群的尿液NAG进行检测 ,同时采用速率法作血尿素氮 (BUN)、血肌肝 (Cr)的测定。结果 :CRF患者尿液NAG水平 (6 2 .88± 17.36u/gCr) (12 0例 )与健康对照组(11 2 9± 2 0 7u/gCr) (4 0例 ) ,有极显著性差异 (P <0 0 1) ,血BUN水平 (分别为 16 42 ±6 17mmol/L5 .15± 0 .99mmol/L) ,血Cr水平 (分别为 6 6 9 76± 2 5 2 0 2umol/L95 .0 3± 17.86umol/L)差异均具极显著性 (P <0 0 1)。而不同含量的BUN ,血Cr和尿Cr对CRF患者尿液NAG水平的影响无明显差异。结论 :CRF患者尿液NAG水平证实了肾脏肾小管功能的不可逆性损害 ,有一定的临床意义和实用价值。     

China introduce new bird flu measures ahead of spring period

Background Restoration of blood flow to the ischemic liver lobes may paradoxically exacerbate tissue injury, which is called hepatic ischemia/reperfusion injury （IRI）. Toll-like receptor 4 （TLR4）, expressed on several liver cell types, and the nuclear factor-kappa B （NF-KB） signaling pathway are crucial to mediating hepatic inflammatory response. Because IRI is essentially a kind of profound acute inflammatory reaction evoked by many kinds of danger signals, we investigated TLR4/NF-KB signaling pathway activation in a murine model of partial hepatic IRI. Methods Wild-type mice （WT, C3H/HeN） or TLR4 mutant mice （C3H/HeJ） were subjected to 45 minutes of partial hepatic ischemia followed by 1 hour, 3 hours of reperfusion. Sham group accepted the same procedure without the obstruction of blood supply. At the end of reperfusion, the compromise of liver function and the histological change of liver sections were measured as the severity of liver injury. The level of endotoxin in the portal vein was measured by limulus assay. NF-KB activation was determined by electrophoretic mobility shift assay （EMSA）. The levels of tumor necrosis factor-a （TNF-a） and intedeukin-1β （IL-1β） in systemic blood after hepatic IRI were assessed by enzyme-linked immunosorbent assay （ELISA）. Results The compromise of liver function and the morphological injuries in mutant mice were relieved more markedly than those in WT mice after partial hepatic IRI. NF-KB activation in WT mice was stronger than that in TLR4 mutant mice, and both were stronger than those in the sham operated mice （P〈0.01）. Endotoxin in each group was undetectable. The levels of TNF-α and IL-1β in systemic blood were elevated in both strains, but lower in the sham operated group. These mediators were significantly decreased in TLR4 mutant mice compared with those in WT mice （P〈0.01）. Conclusions The TLR4/NF-KB signaling pathway may mediate hepatic IRI triggered by endogenous danger signals. Inhibition of the TLR4/NF-KB pathway may be a potential therapeutic target for attenuating ischemia/reperfusion-induced tissue damage in some clinical settings.