褪黑素对免疫性肝损伤小鼠自由基和细胞因子的影响

目的　研究褪黑素对小鼠免疫性肝损伤的保护作用。方法　在诱导BCG +LPS免疫性肝损伤模型的基础上 ,用分光光度法检测血浆中ALT、AST、NO水平和肝匀浆MDA、SOD含量 ;L92 9细胞株法检测血浆中TNF α的生物学活性 ;胸腺细胞增殖法测定血浆中IL 1活性。结果　在BCG+LPS诱导的免疫性肝损伤中 ,褪黑素 (0 2 5 ,1,4mg·kg-1)ig预防给药均明显降低免疫性肝损伤小鼠增高的血浆ALT、AST活性 ,且以 1mg·kg-1的剂量作用最明显 ;并能减少肝匀浆MDA含量 ,使降低的肝匀浆SOD活性升高 ,抑制免疫性肝损伤小鼠血浆NO、TNF α和IL 1的升高。结论　褪黑素对小鼠免疫性肝损伤具保护作用     

二硫代氨基甲酸吡咯烷对小鼠免疫性肝损伤的抑制作用

目的探讨二硫代氨基甲酸吡咯烷(PDTC)对免疫性肝损伤的抑制作用及其机制。方法设正常对照、脂多糖(LPS)、卡介苗(BCG)、BCG+LPS、PDTC和BCG+PDTC+LPS组。除正常对照、LPS和PDTC组外,其余各组小鼠经尾静脉注射BCG(每只2.5mg)。10d后,LPS和BCG+LPS组分别给予LPS(0.2mg·kg-1,ip),PDTC和BCG+PDTC+LPS组在给予LPS前24和2h分别给予PDTC(100mg·kg-1,ip),对照组给予等体积生理盐水。每组15只小鼠用于观察LPS处理后72h的死亡率;每组6只小鼠于LPS处理后1.5h处死,取肝脏,用RT-PCR检测肝脏组织肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)mRNA表达水平,用凝胶电泳迁移率分析法测定肝脏核因子κB(NF-κB)结合活性;每组12只小鼠于LPS处理后6h取血,处死,留取肝脏,测定血清谷丙转氨酶(GPT)活性、一氧化氮(NO)水平和肝组织还原型谷胱甘肽(GSH)含量,制备肝组织切片进行HE染色,观察组织病理变化。结果与正常对照组比较,BCG和LPS组小鼠肝脏炎症细胞明显增加,血清GPT活性升高,肝脏GSH含量显著下降,肝脏TNF-α与IL-1β mRNA表达增强,各组均未见小鼠死亡;PDTC组除血清GPT活性升高外,上述其他指标均未发生明显改变。与BCG和LPS组比较,BCG+LPS组血清GPT活性进一步升高,并伴有大面积肝脏坏死和大量炎症细胞浸润,肝脏NF-κB结合活性显著升高,TNF-α和IL-1β表达进一步增强,GSH水平下降,血清NO水平增加,小鼠死亡率40%。与BCG+LPS组比较,PDTC预处理明显抑制BCG+LPS引起的肝脏NF-κB活性、TNF-α及IL-1β mRNA表达增强,升高肝脏GSH含量,降低血清GPT活性和NO水平,减轻BCG+LPS引起的肝脏炎症和坏死,未见小鼠死亡。结论PDTC可抑制BCG+LPS引起的小鼠免疫性肝损伤,其机制可能与其抗炎和抗氧化作用有关。     

秃疮花提取物对小鼠免疫性肝损伤的保护作用

目的　探讨秃疮花提取物 (DLF)对卡介苗 (BCG)和脂多糖 (LPS)诱导的小鼠免疫性肝损伤的影响。方法　ivBCG和LPS诱导小鼠免疫性肝损伤 ,在注射LPS前 ,小鼠ip不同剂量的DLF(0 5、1 0、2 0g·kg-1) ,连续 10d。观察血清谷丙转氨酶 (ALT)、谷草转氨酶 (AST)、乳酸脱氢酶 (LDH)的活性及血清白蛋白 (ALB)、球蛋白 (GLB)含量变化 ,测定肝组织匀浆中脂质过氧化产物丙二醛 (MDA)含量和超氧化物歧化酶(SOD)活性 ,同时进行肝组织病理学观察。结果　不同剂量的DLF治疗组小鼠血清ALT、AST、LDH活性及肝组织匀浆MDA含量均低于模型组 ,血清蛋白维持正常比例 ,且肝组织损伤不同程度地减轻。结论　秃疮花提取物对BCG和LPS诱导的小鼠免疫性肝损伤具有一定的保护作用     

白芍总苷对卡介苗加脂多糖引起的小鼠免疫性肝损伤的保护作用

目的　研究白芍总苷对小鼠免疫性肝损伤的保护作用。方法　在建立BCG +LPS诱导免疫性肝损伤小鼠模型的基础上 ,分光光度法检测血清中ALT、AST、NO水平和肝匀浆MDA、GSH Px、SOD含量 ;放免法检测TNF α的生物学活性 ;细胞增殖法测定脾淋巴增殖反应。结果　白芍总苷 (6 0、12 0、2 4 0mg·kg-1)ig给药可明显降低免疫性肝损伤小鼠增高的血清ALT、AST活性 ,同时能减少肝匀浆MDA含量 ,使降低的肝匀浆GSH Px、SOD活性升高 ,进一步研究发现白芍总苷可明显抑制免疫性肝损伤小鼠血清NO和TNF α的产生。白芍总苷还可抑制小鼠腹腔巨噬细胞TNF α的产生 ,对ConA诱导的脾淋巴增殖反应具有恢复作用 ,而对LPS诱导的脾淋巴增殖反应无明显影响。结论　白芍总苷对免疫性肝损伤具有保护作用。     

来氟米特对免疫性肝损伤的影响

目的　研究来氟米特对小鼠免疫性肝损伤的影响。方法　利用BCG+LPS诱导免疫性肝损伤;分光光度法检测血中ALT ,AST和NO水平及肝匀浆MDA和GSHpx含量;ELISA法测定血中TNF-α含量;细胞增殖法测定IL-1,IL-2及ConA诱导的脾淋巴细胞增殖反应。结果　在BCG+LPS诱导的免疫性肝损伤中,来氟米特(4,12 ,36mg·kg^-1 )ig给药明显降低免疫性肝损伤小鼠增高的血浆ALT和AST活性及肝匀浆MDA含量,使降低的肝匀浆GSHpx水平增高。进一步研究发现来氟米特明显抑制免疫性肝损伤小鼠TNF-α的产生,降低增高的血清NO水平,抑制PM_Ф产生过高的IL-1,对低下的IL-2产生和ConA诱导的脾淋巴细胞增殖反应有进一步抑制作用。结论　来氟米特对免疫性肝损伤具有保护作用     

氧化苦参碱对BCG+LPS诱导小鼠免疫性肝损伤的保护作用

目的 观察氧化苦参碱(OM)对卡介苗(BCG)+脂多糖(LPS)诱导的BALB/c小鼠免疫性肝损伤后肝组织匀浆中一氧化氮(NO)、诱生型一氧化氮合酶(iNOS)、肿瘤坏死因子(TNF)、白介素1(IL-1)活性的影响.方法 除阴性对照组外,给予其余小鼠BCG+LPS诱导建立免疫性肝损伤小鼠模型,氧化苦参碱高、中、低剂量灌胃给药10d后,取肝组织匀浆,测定各组小鼠肝匀浆中的NO、iNOS及TNF、IL-1.结果 OM可明显降低肝匀浆中的NO、iNOS、TNF、IL-1含量(P<0.01).结论 OM对BALB/c小鼠免疫性肝损伤有明显的保护作用,保肝机制可能与其增强抗氧化活性有关.     

丝毛飞廉总黄酮对小鼠免疫性肝损伤的保护作用

目的研究丝毛飞廉总黄酮对卡介苗(BCG)+脂多糖(LPS)致小鼠急性免疫性肝损伤的保护作用。方法小鼠尾静脉注射BCG+LPS造模后,ig给予丝毛飞廉总黄酮,测定小鼠脏器指数、血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的含量及小鼠肝组织中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量。结果模型组脏器指数及ALT、AST与空白组均有显著性差异,表明模型建立成功;给药组与造模组比较,小鼠脏器指数、AST、ALT的含量、SOD的活性及MDA的含量均有显著性差异。结论丝毛飞廉总黄酮对BCG+LPS致小鼠免疫性肝损伤具有保护作用。     

Protective effect of total flavonoids from Garduus crispus on immunological livery injury in mice induced by BCG + LPS replication

目的 研究丝毛飞廉总黄酮对卡介苗(BCG)+脂多糖(LPS)致小鼠急性免疫性肝损伤的保护作用.方法 小鼠尾静脉注射BCG+ LPS造模后,ig给予丝毛飞廉总黄酮,测定小鼠脏器指数、血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的含量及小鼠肝组织中超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量.结果 模型组脏器指数及ALT、AST与空白组均有显著性差异,表明模型建立成功;给药组与造模组比较,小鼠脏器指数、AST 、ALT的含量、SOD的活性及MDA的含量均有显著性差异.结论 丝毛飞廉总黄酮对BCG+LPS致小鼠免疫性肝损伤具有保护作用.     

N-乙酰半胱氨酸对小鼠免疫性肝损伤的影响

目的研究N-乙酰半胱氨酸(NAC)对卡介苗(BCG)与细菌脂多糖(LPS)引起小鼠免疫性肝损伤的影响。方法建立BCG/LPS引起的小鼠免疫性肝损伤模型。采用两种处理方式给予NAC:方式A,于LPS处理前4h和15min分别经腹腔注射给予NAC(预处理);方式B,于LPS处理后0h和4h分别经腹腔注射NAC(后处理)。LPS处理后8h剖杀动物,取血和肝脏,并检测血清丙氨酸氨基转移酶(ALT)活性与一氧化氮(NO)水平、肝脏组织谷胱甘肽(GSH)与丙二醛(MDA)含量以及肿瘤坏死因子α(TNF-α) mRNA表达水平。结果与模型组比较,NAC预处理组小鼠血清ALT活性下降,肝脏TNF-α mRNA表达明显减少,而体内NO生成和肝脏脂质过氧化水平无改变;NAC后处理组与模型组相比,小鼠死亡率升高,血清NO生成增加,肝脏GSH含量进一步下降,而小鼠血清ALT活性未见明显改变。结论NAC对小鼠免疫性肝损伤有双重效应,NAC预处理对抗BCG/LPS引起的小鼠免疫性肝脏损伤,NAC后处理加重BCG/LPS引起的氧化应激并升高动物死亡率。     

七味净肝灵对卡介苗联合脂多糖诱导的小鼠免疫性肝损伤的保护作用及其机制

目的：研究七味净肝灵（牛大力、黑老虎、地耳草、叶下珠、虫牙药、白花蛇舌草、甘草）对卡介苗（BCG）+脂多糖（LPS）诱导的免疫性肝损伤小鼠的保护作用及其作用机制。方法：建立BCG+ LPS致小鼠免疫性肝损伤模型,取血,收集肝脏,脾脏和胰腺。生化法测定血清中ALT, AST, MDA, SOD的活性或含量,ELISA法检测肝组织中IL-4,IL-6和NO含量,Western-blot分析肝组织中TNF-α和NF-κB蛋白的表达情况;HE染色,显微镜观察肝组织病理改变。结果：七味净肝灵各剂量组可降低免疫性肝损伤小鼠血清或肝组织中ALT、AST、MDA、IL-4,IL-6和NO的活性或含量,抑制肝组织中TNF-α和NF-κB蛋白的表达,升高SOD活性;病例检查显示其各剂量组均能显著改善肝组织坏死损伤。结论：七味净肝灵对BCG+ LPS诱导的小鼠免疫性肝损伤有明显的保护作用,其机制可能通过抗脂质过氧化、抑制肝内的炎症反应及细胞毒性作用来介导保肝作用。     

二苯乙烯低聚体对小鼠实验性肝损伤的影响

目的　研究二苯乙烯低聚体(Gn-3)对各种不同类型实验性肝损伤的影响。方法　用小鼠CCl4、醋氨酚和免疫性肝损伤模型,以血清ALT水平,肝脏MDA和GSH含量,肝脏指数和光镜下组织病理变化为观测指标,观察Gn-3预防给药对肝损伤的影响。结果　Gn-3预防给药3d可降低上述3种类型肝损伤小鼠血清ALT水平、肝脏MDA含量,改善组织病理变化,但对肝脏GSH含量无显著影响。结论　Gn-3对3种不同类型的肝损伤均有不同程度的保护作用。     

Upregulation of TNF-α and IL-6 mRNA in mouse liver induced by bacille Calmette-Guerin plus lipopolysaccharide

AIM: To investigate the mechanism of immunological liver injury induced by bacille Calmette-Guerin (BCG) plus lipopolysaccharide (LPS). METHODS: Mice were injected via the tail vein with 125 mg/kg BCG, and 12 d later, the mice were injected intravenously with different doses of LPS (125, 250, or 375 microg/kg). Serum alanine aminotransferase (ALT) activity and liver pathological changes were examined. The expression of tumor necrosis factor (TNF)- alpha, interleukin (IL)-6, lipopolysaccharide binding protein (LBP) and CD14 mRNA, and NF-kappaB and IkappaB-alpha protein in mouse liver at different time points after BCG and LPS injection were measured using RT-PCR, immunohistochemistry and Western blotting analysis, respectively. RESULTS: The activity of serum ALT in mice treated with BCG and LPS was significantly increased. Different degrees of liver injury, such as inflammatory cell infiltration, spotty necrosis, piecemeal necrosis, even bridging necrosis, could be seen in liver sections from mice after BCG and LPS administration. Furthermore, the levels of TNF-alpha and IL-6 mRNA in mouse liver were significantly elevated after administration of BCG plus LPS (P<0.05). The levels of LBP and CD14 mRNA in mouse liver were markedly upregulated after treatment with BCG and LPS, and treatment with BCG alone led to an increase in CD14 mRNA in mouse liver. Finally, immunoreactivity for NF-kappaB p65 was predominantly detected in hepatocyte nuclei from mice treated with BCG plus LPS, compared with the normal group. Protein levels of IkappaB-alpha were strikingly decreased by LPS or BCG plus LPS treatment, compared with the normal group or BCG group. CONCLUSION: TNF-alpha and IL-6 mRNA were partially involved in early immunological liver injury induced by challenge with small doses of LPS after BCG priming. Upregulation of TNF-alpha and IL-6 mRNA might be related to increases in LBP and CD14 mRNA expression and activation of NF-kappaB. Furthermore, BCG priming in immunological liver injury may occur via upregulation of CD14 mRNA expression in mononuclear cell infiltration into the liver.     

联苯双酯对大鼠黄曲霉毒素B1代谢及肝毒性的影响

目的研究抗肝炎药联苯双酯对大鼠黄曲霉毒素B1代谢和肝毒性的影响.方法大鼠po联苯双酯300 mg*kg-1*d-1, 连服3 d后ip黄曲霉毒素B1 1.5 mg*kg-1.给黄曲霉毒素B1 16 h后测定血清ALT和AST水平,观察联苯双酯对黄曲霉毒素B1引起肝损伤的保护作用以及对体外代谢的影响.结果联苯双酯(300 mg*kg-1*d-1,连服3 d)可明显降低黄曲霉毒素B1引起的大鼠血清转氨酶升高,增加低毒代谢产物AFM1的生成.联苯双酯还可增加大鼠肝脏细胞色素P450总量和胞浆GSH含量,诱导P450 2B1介导的PROD和GST的活性.此外,联苯双酯对P450 3A介导的红霉素脱甲基酶和P450 1A介导的EROD也有一定的诱导作用.结论联苯双酯可通过增加大鼠肝脏对AFB1代谢的解毒功能起到肝保护作用.     

丹皮总甙对小鼠免疫性肝损伤的保护作用

目的研究丹皮总甙（TGM）对小鼠免疫性肝损伤的保护作用。方法：小鼠分别尾ivBCG和LPS后，检测其血清ALT和AST活性、TPr含量及其脏器重量指数，并用硫代巴比妥酸法测其血清与肝组织中LPO含量。结果：TGM50、100mg·kg(－1)·d(－1)（ig），连用9d，可显著抑制小鼠血清ALT和AST活性，降低其血清与肝组织中LPO含量，并减轻其增大的脾脏重量指数。结论：TGM预防性给药对BCG＋LPS诱导的小鼠免疫性肝损伤具有一定的保护作用。     

Cocaine hepatotoxicity and its potentiation by lipopolysaccharide: treatment and gender effects

This study was conducted to investigate the effect of a 7-day treatment as well as the influence of gender on cocaine hepatotoxicity (CH). Lipopolysaccharide (LPS) potentiation of CH was also investigated. Male and female CF-1 mice were orally administered 20 mg/kg body weight cocaine hydrochloride once daily for 7 days. Four hours after the last cocaine administration, the mice were administered 12 x 10(6) EU LPS (or equal volume of sterile saline) intraperitoneally. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were evaluated as indices of liver injury. Blood and liver glutathione (GSH), glutathione reductase (GRx), and catalase (CAT) activities were also determined to investigate the oxidation stress induced by the treatment. Plasma ALT and AST concentrations were elevated in all males receiving cocaine alone or cocaine + LPS. Furthermore, blood GSH and CAT were decreased and GRx activity was elevated in the same males. Histological analysis revealed a high degree of focal necrosis in the male cocaine group, and severe necrosis in the male cocaine + LPS group. Unlike males, females showed no effect of either cocaine alone or cocaine + LPS treatments. These results indicate that gender plays a significant role in CH and its potentiation by LPS and lengthening the administration by two treatments increased the severity of cocaine + LPS hepatotoxicity dramatically in male mice.     

黄芩苷对卡介苗加脂多糖诱导免疫性肝损伤小鼠的作用

目的　研究黄芩苷对免疫性肝损伤小鼠的作用。方法　采用卡介苗加脂多糖 (BCG+LPS)诱导小鼠免疫性肝损伤模型,通过检测血清谷丙转氨酶(ALT)的活性,计算脾脏等脏器指数并检查肝组织的病理损伤程度,研究黄芩苷的护肝作用。结果　黄芩苷对BCG+LPS诱导的小鼠免疫性肝损伤有明显保护作用,可降低肝损伤小鼠血清ALT的活性和肝脏、胸腺指数,与模型对照组比较有显著差异(P<0. 05~0. 01),且可不同程度减轻肝脏病理损伤。结论　黄芩苷对小鼠免疫性肝损伤有保护作用,对小鼠的免疫功能有调节作用。     

Tissue factor antisense deoxyoligonucleotide prevents monocrotaline/LPS hepatotoxicity in mice

Tissue factor (TF) is a membranous glycoprotein that functions as a receptor for coagulation factor VII/VIIa and activates the coagulation system when blood vessels or tissues are damaged. TF was upregulated in our monocrotaline (MCT)/lipopolysaccharide (LPS) hepatotoxicity model. We tested the hypothesis that TF‐dependent fibrin deposition and lipid peroxidation in the form of oxidized low‐density‐lipoprotein (ox‐LDL) accumulation contribute to liver inflammation induced by MCT/LPS in mice. In the present study, we blocked TF using antisense oligodeoxynucleotides against mouse TF (TF‐ASO). TF‐ASO (5.6 mg kg^?1) was given i.v. to ND4 male mice 30 min after administration of MCT (200 mg kg^?1) p.o. followed after 3.5 h by LPS i.p. (6 mg kg^?1). Blood alanine aminotransferase (ALT), TF, ox‐LDL, platelets, hematocrit and keratinocyte‐derived chemokine (KC) levels were evaluated in different treatment groups. Fibrin deposition and ox‐LDL accumulation were also analyzed in the liver sections using immunofluorescent staining. The results showed that TF‐ASO significantly restored blood ALT, hematocrit and KC levels, distorted after MCT/LPS co‐treatment, as well as preventing the accumulation of ox‐LDL and the deposition of fibrin in the liver tissues, and thereby inhibited liver injury caused by MCT/LPS. In a separate experiment, TF‐ASO administration significantly prolonged animal survival. The current study demonstrates that TF is associated with MCT/LPS‐induced liver injury. Administration of TF‐ASO successfully prevented this type of liver injury. Copyright © 2012 John Wiley & Sons, Ltd.