Attenuation of graft injury in porcine liver transplantation from non-heart beating donor by FR167653

BACKGROUND/AIMS: Orthotopic liver transplantation (OLTx) from non-heart beating donor (NHBD) often involves hepatic warm ischemia and reperfusion injury which is triggered by the inflammatory cytokines. This study was carried out to investigate whether a newly synthesized cytokine suppressive anti-inflammatory agent, FR167653, attenuates graft injury in OLTx from NHBD. METHODOLOGY: Porcine OLTx from NHBD was performed. No-heart beating time was scheduled to be 60 minutes. Animals were divided into two groups: no treatment control (CT) group (n=5), and FR167653 treated (FR) group (n=5), in which FR167653 was administered intravenously before the aortic cross clamp in the donor, and before and after the hepatic allograft reperfusion in the recipient continuously. RESULTS: Four out of five pigs died within 24 hours and one on postoperative day 1 from graft liver failure in the CT group, while two pigs died on day 3, and three survived more than 7 days in the FR group (p<0.05). Microcirculatory disturbance was attenuated, liver injury was lessened, and ATP resynthesis was enhanced in the FR group. Additionally, FR167653 inhibited neutrophils infiltration in the liver tissue, and suppressed release of inflammatory cytokines after OLTx from NHBD. CONCLUSIONS: The treatments with FR167653 successfully prevented graft injury after OLTx from NHBD by means of improvement of liver microcirculation, and attenuation of neutrophils activation. The inhibitory effect of FR167653 on the release of inflammatory cytokines played an important role in the liver graft protection.     

Attenuation of microcirculatory disturbance after liver ischemia by newly synthesized inflammatory cytokine suppressor,FR167653

BACKGROUND/AIMS: Inflammatory cytokines, such as interleukin-1 beta and tumor necrosis factor-alpha, which activate neutrophils, contribute to hepatic warm ischemia-reperfusion injury. However, the role of the cytokines in hepatic microcirculation immediately after reperfusion is still unclear. This study was carried out to investigate whether FR167653, a dual inhibitor of interleukin-1 beta and tumor necrosis factor-alpha, attenuates hepatic microcirculatory disturbance at the initial phase of reperfusion following liver ischemia. METHODOLOGY: Adult mongrel dogs were subjected to 90 minutes of liver ischemia by a Pringle's maneuver under portosystemic bypass. The animals were divided into two groups: a control group (n = 10), subjected to hepatic warm ischemia only, and a FR167653 administered group (n = 5), which received 1 mg/kg/h FR167653 for 4 hours since 30 minutes before the ischemia to 2 hours after the reperfusion continuously. Seven days animal survival, hepatic tissue blood flow, liver function test, hepatic venous blood concentration of endothelin-1 and plasminogen activator inhibitor-1, liver tissue biochemistry, and histopathology were analyzed. RESULTS: The treatment with FR167653 attenuated microcirculatory disturbance, lessened liver injury, enhanced adenine nucleotides resynthesis, and improved animal survival after liver ischemia. In addition, FR167653 significantly inhibited release of both endothelin-1 and plasminogen activator inhibitor-1 from the liver cells. CONCLUSIONS: These results suggest that the inflammatory cytokines induce microcirculatory disturbance in the initial phase of reperfusion following liver ischemia.     

The effect of FR167653 on cerebral ischemia-reperfusion injury after retrograde cerebral perfusion in a canine model

Retrograde cerebral perfusion (RCP) has recently been reported to be useful for the repair of aortic arch aneurysms. However, there is a possibility that RCP supplies a limited amount of blood to the brain [1] and ischemia-reperfusion injury may occur after RCP. FR167653 (FR) is characterized as a potent suppressant of interleukin-1 and tumor necrosis factor-. We investigated the role of FR in preventing cerebral ischemia-reperfusion injury after RCP in a canine model. A total of 12 mongrel dogs was divided into two groups: in the FR group (n=6), FR167653 (1 mg/kg/hour) was continuously administered during the period of RCP and rewarming; in the control group (n=6), a physiological saline solution was administered at the same dosage as the FR167653 during the same period. Following hypothermia (20°C) using cardiopulmonary bypass and circulatory arrest, RCP was performed by infusing oxygenated blood via the bilateral internal maxillary veins for 60 minutes at a perfusion pressure of 25 mmHg. The cerebral blood flow (CBF), cerebral metabolic rate for glucose (CMRGlu) and oxygen (CMRO₂), and excretion of carbon dioxide (ExCO₂) were measured. These results were expressed as the percentage of change from baseline values established immediately after anesthesia. CBF was significantly (p<0.05) higher in the FR group than in the control group at 40 (159±25% and 82±21%, respectively) and 60 minutes (177±30% and 83±14%, respectively) after RCP. The lactate/pyruvate ratio of blood returned from the brain tissues was significantly (p<0.05) lower in the FR group than in the control group at 40 and 60 minutes after RCP. CMRGlu was significantly (p<0.05) higher in the FR group than in the control group 60 minutes after RCP. There was no significant difference in CMRO₂ and ExCO₂ between the two groups. It is concluded that FR167653 appears to be effective in protecting the brain from ischemia-reperfusion injury after RCP.Presented in part at the 40th Annual World Congress International College of Angiology, Lisbon, Portugal, June 1998.     

Effect of FR167653 on Small Bowel Ischemia-Reperfusion Injury in Dogs

IL-1 and TNF- are known to be pleiotropiccytokines associated with various inflammatoryconditions such as small intestinal injury afterischemia-reperfusion. FR167653 has been characterized asa potent suppressant of IL-1 and TNF-production. The effect of FR167653 on intestinalreperfusion injury was investigated in a warm ischemiamodel of the canine gut. Sixteen mongrel dogs weredivided into two groups: a control group and a FR groupto which FR167653 was administered. Both the superiormesenteric artery and vein were clamped for 2 hr.Arterial pH, hepatic venous hemoglobin oxygensaturation, intramucosal pH, and the survival rate werewell maintained in the FR group in comparison with thecontrol group after reperfusion. FR167653 inhibited theexpression of IL-1 mRNA. Histologically,ischemia-reperfusion injury was more severe in the control groupthan the FR group. This study suggests that FR167653inhibits proinflammatory cytokines and amelioratesischemia-reperfusion injury of the smallintestine.     

The effect of FR167653 in a canine total hepatic vascular exclusion model

BACKGROUND/AIMS: Though liver grafts from non-heart-beating donors are now attracting much attention, these grafts inevitably suffer from severe warm ischemia. The aim of this study was to evaluate the effect of TNF-alpha and IL-1 suppression on warm ischemia-reperfusion injury in a canine total hepatic vascular exclusion model. METHODOLOGY: Warm ischemia was induced by 1-h total hepatic vascular exclusion with active splenofemuro-juglar bypass. Animals were divided into two groups. FR167653 (1 mg/kg/hr) was administered via the portal vein from 30 min prior to ischemia until 2 h after reperfusion to the FR group (n = 7), and a vehicle was administered to the control group (n = 7). The serum alanine aminotransferase, aspartate amino-transferase, lactate dehydrogenase, and hyaluronic acid levels were measured. Hepatic tissue blood flow was also measured. Liver specimens were harvested for histological study, and polymorphonuclear neutrophils were counted. RESULTS: Serum liver enzymes were significantly (p < 0.05) lower, and hepatic tissue blood flow was kept significantly (p < 0.05) better in the FR group than in the control. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p < 0.05) lower in the FR group than in the control group. CONCLUSIONS: FR167653 provides protective effects on hepatic warm ischemic injury in a canine total hepatic vascular exclusion model.     

Vitamin E attenuates myocardial ischemia-reperfusion injury in murine AIDS

The incidence of myocardial infarction in patients who have the aquired immunodeficiency syndrome (AIDS) is increasing. However, no effective therapeutic agents have been discovered to reduce myocardial ischemia-reperfusion (I/R) injury in pathologies associated with AIDS. The aim of this study was to determine if infarct size is increased in murine AIDS after I/R injury and if I/R injury could be attenuated with vitamin E supplementation. Three groups of mice were studied: control, murine AIDS, and murine AIDS with vitamin E supplementation. Anesthetized mice were subjected to 30 min of left anterior descending coronary artery occlusion and 120 min of reperfusion. The hearts in mice that had murine AIDS had a larger infarct size compared to controls after I/R injury. Vitamin E supplementation significantly reduced infarct size and inhibited polymorphonuclear neutrophil (PMN) CD11b expression (p<0.05). However, vitamin E supplementation did not affect PMN reactive oxygen species (ROS) production and platelet CD62p expression. These results suggest that the reduction of myocardial I/R injury with vitamin E supplementation may be the result of the inhibition of PMN CD11b expression. Vitamin E may be a promising prophylactic agent for the reduction of the severity of myocardial I/R injury in patients who have AIDS.     

FR128998 ameliorates liver injury in extended liver resection with ischemia in dogs

BACKGROUND/AIMS: Platelet-activating factor is one of the most potent phospholipid mediators associated with inflammatory conditions such as ischemia and reperfusion injury. FR128998 (FR) is a novel platelet-activating factor receptor antagonist. In this study, we evaluated the effect of FR during an extended liver resection with ischemia in a canine model. METHODOLOGY: Animals were divided into two groups: the control group (n = 8), and the FR-treated group (n = 7) in which FR was administered via the portal vein. While the right portal pedicle was clamped for 60 min, the left portal branch remained patent to avoid splanchnic congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) was resected. Hepatic venous blood was collected to measure GPT, GOT, and LDH levels. Hepatic tissue blood flow was measured by a laser Doppler flow meter. The liver specimen was harvested for histological study. RESULTS: GPT, GOT, and LDH levels after reperfusion were significantly (P < 0.05) lower in the FR-treated group than in the control group. Hepatic tissue blood flow was maintained significantly (P < 0.05) higher in the FR-treated group than in the control group. Histologically, accumulation of polymorphonuclear neutrophils significantly (P < 0.05) decreased in the FR-treated group compared with the control group. The 2-day survival rate was statistically (P < 0.05) better in the FR-treated group than in the control group. CONCLUSIONS: FR128998 provides a protective effect for liver parenchyma and sinusoidal endothelial cells during extended liver resection with ischemia.     

免疫性肝损伤相关细胞因子研究进展

乙型肝炎病毒等多种诱因导致免疫性肝损伤,促成肝细胞的病变的重要因素是免疫应答中产生的细胞因子。本文综述了有关细胞因子与免疫性肝损伤发病机制的实验研究进展。     

S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon

Chronic ethanol consumption by baboons (50% of energy from a liquid diet) for 18 to 36 mo resulted in significant depletion of hepatic S-adenosyl-L-methionine concentration: 74.6 +/- 2.4 nmol/gm vs. 108.9 +/- 8.2 nmol/gm liver in controls (p less than 0.005). The depletion was corrected with S-adenosyl-L-methionine (0.4 mg/kcal) administration (102.1 +/- 15.4 nmol/gm after S-adenosyl-L-methionine-ethanol, with 121.4 +/- 11.9 nmol/gm in controls). Ethanol also induced a depletion of glutathione (2.63 +/- 0.13 mumol/gm after ethanol vs. 4.87 +/- 0.36 mumol/gm in controls) that was attenuated by S-adenosyl-L-methionine (3.89 +/- 0.51 mumol/gm in S-adenosyl-L-methionine-methanol vs. 5.22 +/- 0.53 mumol/gm in S-adenosyl-L-methionine controls). There was a significant correlation between hepatic S-adenosyl-L-methionine and glutathione level (r = 0.497; p less than 0.01). After the baboons received ethanol, we observed the expected increase in circulating levels of the mitochondrial enzyme glutamic dehydrogenase: 95.1 +/- 21.4 IU/L vs. 13.4 +/- 1.8 IU/L; p less than 0.001, whereas in a corresponding group of animals given S-adenosyl-L-methionine with ethanol, the values were only 30.3 +/- 7.1 IU/L (vs. 9.6 +/- 0.7 IU/L in the S-adenosyl-L-methionine controls). This attenuation by S-adenosyl-L-methionine of the ethanol-induced increase in plasma glutamic dehydrogenase (p less than 0.005) was associated with a decrease in the number of giant mitochondria (assessed in percutaneous liver biopsy specimens), with a corresponding change in the activity of succinate dehydrogenase, a mitochondrial marker enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of leflunomide on immunological liver injury in mice

AIM: To study the effect of leflunomide on immunological liver injury (ILI) in mice,METHODS: ILI was induced by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10μg lipopolysaccharide (LPS) in 0.2mL saline (BCG+LPS). Thealanine aminotransferase (ALT), aspartate aminotransferase(AST), nitric oxide (NO) level in plasma and molondiadehyde(MDA), glutathione peroxidase (GSHpx) in liver homogenate were assayed by spectroscopy. The serum content of tumor necrosis factors-α (TNF-α) was determined by ELISA.Interleukin-1 (IL-1), interleukin-2 (IL-2) and Concanavalin A (ConA)-induced splenocyte proliferation response were determined by methods of 3H-infiltrated cell proliferation.RESULTS: Leflunomide (4, 12, 36 mg.kg^-1) was found to significantly decrease the serum transaminase (ALT, AST)activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Leflunomide (4,12,36 mg.kg^-1) significantly lowered TNF-α and NO level in serum, and IL-1 produced by intraperitoneal macrophages(PMФ). Moreover, the decreased IL-2 production and ConAinduced splenocyte proliferation response were further inhibited.CONCLUSION: These findings suggested that leflunomide had significant protective action on ILI in mice.     

FR167653, a p38 mitogen-activated protein kinase inhibitor, aggravates experimental colitis in mice

AIM： To investigate the effects of FR167653 on the development of dextran sulfate sodium （DSS）-induced colitis in mice. METHODS： BALB/c mice were fed rodent chow containing 3.5% （wt/wt） DSS. The recipient mice underwent intra-peritoneal injection of vehicles or FR167653 （30 mg/kg per day）. The mice were sacrificed on day 14, and the degree of colitis was assessed. Immunohistochemical analyses for CD4^＋ T cell and F4/80^＋ macrophage infiltration were also performed. Mucosal cytokine expression was analyzed by RT-PCR. RESULTS： The body weight loss was more apparent in the FR167653-treated DSS mice than in the vehicletreated DSS mice. The colon length was shorter in the FR167653-treated DSS mice than in the vehicle-treated DSS mice. Disease activity index and histological colitis score were significantly higher in FR167653- than in vehicle-treated DSS animals. Microscopically, mucosal edema, cellular infiltration （CD4 T cells and F4/80 macrophages）, and the disruption of the epithelium were much more severe in FR167653-treated mice than in controls. Mucosal mRNA expression for interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） were found to be markedly reduced in FR167653-treated DSS mice. CONCLUSION： Treatment with FR167653 aggravated DSS colitis in mice. This effect was accompanied by a reduction of mucosal IL-1β and TNF-α expression, suggesting a role of p38 mitogen-activated protein kinase （MAPK）-mediated proinflammatory cytokine induction in host defense mechanisms.     

Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis

Cholestasis occurs in a variety of clinical settings and often results in liver injury and secondary biliary fibrosis. Several matrix metalloproteinases (MMPs) are upregulated in the liver during cholestasis. The function of the major interstitial collagenase, MMP-13, in the initial phase of liver fibrosis is unknown. The aim of this study was to evaluate the role of MMP-13 during the development of cholestasis-induced liver fibrosis by comparing wild-type and MMP-13-deficient mice. Cholestasis was induced by bile duct ligation (BDL) for 5 days or 3 weeks. Activation and proliferation of hepatic stellate cells (HSCs) were detected by immunohistochemistry. Expression of MMP-13 mRNA increased significantly in BDL livers of WT mice. After BDL for 3 weeks liver fibrosis was suppressed in MMP-13-deficient mice versus WT animals. Activation and proliferation of HSCs were also suppressed in livers of MMP-13-deficient mice after BDL. To clarify the mechanism of this suppression, samples from 5-day BDL mice were used for evaluation of liver injury. Compared with those in WT animals, serum ALT and the number of hepatic neutrophils were reduced in MMP-13-deficient mice. Increased expression of the mRNA of inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) was significantly suppressed in livers of MMP-13-deficient mice. Upregulation of fibrogenic markers, for example, transforming growth factor beta1 (TGF-beta1), was also significantly suppressed in livers of MMP-13-deficient mice versus in WT mice. In conclusion, distinct from the known function of interstitial collagenase to reduce liver fibrosis by degrading the extracellular matrix, MMP-13 contributes to accelerating fibrogenesis in cholestatic livers by mediating the initial inflammation of the liver.     

N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury

AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).METHODS: Mice were injected with NAC (300 mg/kg) intraperitoneally 2 h before ischemia. Real-time polymerase chain reaction and western blotting determined ER stress molecules (GRP78, ATF4 and CHOP). To analyze the role of NAC in reactive oxygen species (ROS)-mediated ER stress and apoptosis, lactate dehydrogenase (LDH) was examined in cultured hepatocytes treated by H₂O₂ or thapsigargin (TG).RESULTS: NAC treatment significantly reduced the level of ROS and attenuated ROS-induced liver injury after IRI, based on glutathione, malondialdehyde, serum alanine aminotransferase levels, and histopathology. ROS-mediated ER stress was significantly inhibited in NAC-treated mice. In addition, NAC treatment significantly reduced caspase-3 activity and apoptosis after reperfusion, which correlated with the protein expression of Bcl-2 and Bcl-xl. Similarly, NAC treatment significantly inhibited LDH release from hepatocytes treated by H₂O₂ or TG.CONCLUSION: This study provides new evidence for the protective effects of NAC treatment on hepatocytes during IRI. Through inhibition of ROS-mediated ER stress, NAC may be critical to inhibit the ER-stress-related apoptosis pathway.     

肝脾调补方对小鼠免疫性肝损伤的防护作用

目的:观察中药肝脾调补方对小鼠免疫性肝损伤的防护作用并探讨其药理学机制。方法:采用卡介苗(BCG)+脂多糖(LPS)建立小鼠免疫性肝损伤模型,通过肝脾调补方高、中、低剂量灌胃,观察肝脾调补方对各组小鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)及肝组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平的影响;ELISA法检测肿瘤坏死因子-α(TNF-α)的变化。结果:肝脾调补方可明显降低免疫性肝损伤小鼠血清中ALT、AST、TNF-α水平;减少肝组织匀浆的MDA含量,升高肝匀浆SOD、GSH-Px含量。结论:肝脾调补方对BCG+LPS尾静脉注射造成的小鼠免疫性肝损伤有明显的防护作用,其作用与抗脂质过氧化有关。     

The GLP-1 analog liraglutide attenuates acute liver injury in mice

Introduction and objectivesAcute liver injury is a current health problem with few effective treatments. The present study investigated the hepatoprotective and curative potential of the glucagon-like peptide-1 analog liraglutide against carbon tetrachloride (CCl₄)-induced hepatotoxicity.Materials and methodsMale Swiss mice were subjected to two protocols. The first protocol (Pretreatment) consisted of intraperitoneal (i.p.) treatment with liraglutide (0.057 and 0.118 mg kg⁻¹) or vehicle (distilled water) once daily for 7 days. On days 6 and 7, the animals were challenged with 2% CCl₄ (5 mg kg⁻¹, i.p.). The second protocol (Late treatment) began with an injection of 5% CCl₄ (5 mg kg⁻¹, i.p.) and subsequent treatment with liraglutide (0.057 mg kg⁻¹) or vehicle (distilled water) for 1 day. In both protocols, 24 h after the last administration, blood and bile were collected from anesthetized animals, followed by euthanasia and liver collection. Plasma and bile underwent biochemical analyses, and histological, oxidative stress, and metabolic parameters were evaluated in the liver.ResultsBoth liraglutide treatment protocols attenuated hepatotoxicity that was induced by CCl₄, decreasing plasma levels of hepatic enzymes, stimulating the hepatic antioxidant system, and decreasing centrilobular necrosis, hepatic glycogen, and lipid accumulation. CCl₄ tended to reduce bile lipid excretion, but liraglutide did not influence this parameter.ConclusionsThe present results demonstrated the hepatoprotective and therapeutic effects of liraglutide, which may be attributable to a decrease in liver oxidative stress and the preservation of metabolism. Liraglutide may have potential as a complementary therapy for acute liver injury.     

四氯化碳诱导小鼠急性肝损伤模型的建立和优化

目的通过单次腹腔注射不同剂量的四氯化碳(CCl4)致小鼠急性肝损伤,检测小鼠血浆转氨酶水平的变化,建立适合本研究的小鼠模型。方法采用6~8周龄雄性C57BL/6小鼠单次腹腔注射CCl4诱导急性肝损伤。比较不同剂量的CCl4诱导急性肝损伤小鼠的血浆转氨酶水平。将182只小鼠随机分出32只。32只小鼠随机分为3组CCl4实验组(每组8只)和正常对照组(8只),分别腹腔注射0.1%、0.2%、0.3%的CCl4橄榄油溶液(10 ml/kg)或等体积橄榄油。注射12小时后取血,检测血浆丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的水平。比较0.1%和0.2%剂量组小鼠不同时间点血浆转氨酶水平的变化。将剩余150只小鼠随机分为正常对照组(10只)、实验Ⅰ组(0.1%剂量,70只)、实验Ⅱ组(0.2%剂量,70只),实验组小鼠在造模6、12、16、20、24、48、72小时后取血,检测血浆ALT、AST的水平。结果与正常对照组相比,分别用0.1%、0.2%、0.3%CCl4处理后12小时小鼠血浆ALT、AST均明显升高(P0.05),并呈剂量依赖性。与正常对照组相比,0.1%和0.2%剂量组小鼠血浆ALT、AST的水平在早期均呈上升趋势,并分别在16小时和20小时达到高峰,随后逐渐下降,在72小时接近至正常水平。结论单次腹腔注射CCl4诱导小鼠急性肝损伤呈剂量依赖性。0.1%剂量的CCl4以及该剂量处理后16小时是建立C57BL/6小鼠急性轻度肝损伤的合适剂量与检测转氨酶水平的合适时间点。     

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression.

AIMS: The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX. METHODS AND RESULTS: Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth. CONCLUSION: In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.     

Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumor suppression.

The article by Neilan et al.¹ [May 27(10) issue of thisjournal] is of interest to us. Their group has documented thatiloprost attenuates the doxorubicin (DOX)-induced     

脂联素在小鼠急性肝损伤中的表达及作用

目的: 观察脂联素在小鼠急性肝损伤的表达及作用.方法: 健康♂BALB/c小鼠随机分为3组. 刀豆蛋白A(concanavalin A, ConA)组8只: ConA 30mg/kg 尾静脉注射. 脂联素组5只: 在静脉注射ConA前12 h和2 h, 分别应用脂联素3 mg/kg腹膜内注射. 对照组8只: 尾静脉注射生理盐水10mL/kg. 注射ConA 8 h后处死小鼠, 检测脂联素及ALT血清水平、肝组织病理变化、肝组织脂联素蛋白及mRNA的表达.结果: 脂联素血清水平在脂联素组与对照组无差异, 2组均高于ConA组(15.4±3.0 mg/L,16.5±2.8 mg/L vs 11.8±2.1 mg/L, P <0.05或0.01);肝组织脂联素蛋白表达在脂联素组强于对照组(5.39%±1.72% vs 1.82%±0.36%,P <0.05), 弱于ConA组(10.63±4.35%, P <0.05);肝组织脂联素mRNA表达在脂联素组和ConA组均强于对照组(0.46±0.17, 0.51±0.21 vs0.23±0.05, P <0.05或0.01);血清ALT水平及肝组织炎症程度脂联素组高于对照组(192.50±45.87 U/L vs 44.71±21.29 U/L;21.5±9.2vs 8.4±4.3, 均P <0.05), 低于ConA组(616.00±171.50 U/L, 48.5±8.6, 均P <0.05).结论: 在ConA诱导的急性肝损伤中, 肝组织脂联素蛋白及其mRNA的表达增强, 但血清脂联素水平降低. 脂联素对急性肝损伤小鼠起着抗炎作用.