刀豆蛋白A诱导的急性肝损伤小鼠血浆细胞外组蛋白的变化及意义

目的研究细胞外组蛋白在刀豆蛋白A(Con A)诱导的小鼠急性肝损伤时的水平变化及干预价值。方法小鼠经尾静脉注射Con A(35 mg·kg-1)建立急性肝损伤模型,同时给予特异性抗组蛋白中和抗体进行干预,比较两组小鼠的存活率、肝功能以及相关细胞因子水平的变化。结果给予小鼠Con A后,染毒3 h、9 h、16 h和24h时血清ALT水平升高为(106.5±25.5)IU/L、(769.1±138.2)IU/L、(1340.2±205.9)IU/L和(1304.7±300.7)IU/L,均明显高于对照组[(35.5±3.165)IU/L,P0.01];肝组织病理学检查显示有大量肝细胞发生变性、坏死;Con A染毒小鼠血浆细胞外组蛋白水平亦呈时间依赖方式明显增高,染毒3 h、9 h、16 h和24 h时,细胞外组蛋白相对水平分别为(1.199±0.1087)、(2.467±0.197)、(2.655±0.2295)和(2.631±0.3014),显著高于对照组水平[(0.206±0.024),P0.001];染毒小鼠经特异性抗组蛋白中和抗体干预后,死亡率明显下降,病理学显示肝损伤程度亦得到减轻,其血清IL-6和TNF-α水平分别为(16.98±3.67)pg/ml和(3.25±0.67)pg/ml,较模型组水平显著降低[分别为(238.10±48.56)pg/ml和(16.52±2.43)pg/ml,P0.01]。结论细胞外组蛋白是Con A所致急性肝损伤发病过程中的重要炎性介质,以细胞外组蛋白为靶点进行干预能减轻肝脏炎症反应。     

促红素衍生肽对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用

目的探讨外源性给予人工合成的促红素衍生肽(HBSP)对刀豆蛋白A(Con A)诱导的急性免疫性肝损伤的保护作用。方法采用小鼠尾静脉注射Con A建立急性肝损伤模型,造模后2 h给予HBSP治疗(采用尾静脉注射,8nmol/kg,每6小时1次),造模后6、12、24 h分别测定小鼠血清中ALT、AST水平,并进行肝组织病理学检查评估肝损伤程度。测定造模后12 h肝组织中IL-6、IL-1β、TNF-α、IFN-γ、IL-12、IL-4、IL-10、TGF-β表达水平,通过TUNEL及免疫组化检测(分裂型Caspase-3)评估肝脏内肝细胞凋亡情况。结果在Con A诱导的急性肝损伤小鼠模型中,HBSP给药组血清ALT和AST水平显著低于Con A模型组,并且小鼠肝组织炎症坏死程度明显低于Con A模型组。同时,80 nmol/kg的HBSP给药显著提高了注射致死剂量Con A小鼠的生存率。此外,HBSP在mRNA水平抑制肝脏中促炎因子(IL-6、IL-1β、TNF-α、IFN-γ、IL-12)的表达,促进抑炎因子(IL-4、IL-10)的表达,并显著抑制Con A诱导的急性肝损伤相关的细胞凋亡。结论 HBSP对Con A诱导的急性肝损伤具有较好的保护作用,其机制可能与其抑制炎性反应及肝细胞凋亡有关。     

清肠利肝方对D-氨基半乳糖/脂多糖所致急性肝衰竭小鼠的防护作用

目的:探讨中药组方清肠利肝方对D-氨基半乳糖/脂多糖(D-Gal N/LPS)所致急性肝衰竭小鼠的防护作用并探究其相关机制。方法:将野生型健康C57BL/6雄性小鼠随机分为正常组、急性肝衰竭模型组(简称模型组)和清肠利肝方干预组(简称干预组)。模型组和干预组小鼠腹腔注射D-Gal N(700 mg/kg)LPS(10μg/kg)诱导肝衰竭;干预组小鼠注射D-Gal N/LPS前3天以清肠利肝方灌胃,1次/d。D-Gal/LPS给药6小时后收集小鼠肝脏组织和血清。观察各组小鼠肝脏损伤变化及相关炎症分子的变化情况。结果:模型组小鼠肝脏损伤严重,大片肝组织充血坏死;干预组小鼠肝脏损伤较模型组减轻,促炎因子水平低于模型组,MAPK通路炎症相关蛋白表达降低,差异有统计学意义(P0.05)。结论:清肠利肝方对D-Gal N/LPS所致小鼠急性肝衰竭有明显防护作用,其机制可能与调节MAPK通路而发挥抗炎作用有关。     

海珠益肝加味方对免疫性肝损伤小鼠的防护作用

目的:观察海珠益肝加味方对刀豆球蛋白A(Con A)诱导建立的免疫性肝损伤小鼠的防护作用及作用机制。方法:将40只昆明小鼠随机分为正常组、模型组、醋酸强的松组、海珠益肝加味方组,采用尾静脉注射Con A建立免疫性肝损伤小鼠模型。造模给药8h后眼球取血,检测小鼠血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、白细胞介素-4(IL-4)和白细胞介素-6(IL-6)水平。摘取肝脏,光镜下观察各组肝组织的病理变化,检测肝组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)的水平,测定肝组织NF-κB-p65表达水平。结果:与模型组比较,对照组和海珠益肝加味方组降低血清ALT、AST水平及肝组织MDA水平,降低肝组织NF-κB-p65表达水平,提高血清IL-4、IL-6水平及其肝组织SOD活性,同时海珠益肝加味方组肝脏病理变化程度明显减轻。结论:海珠益肝加味方能有效降低免疫性肝损伤小鼠转氨酶水平,减轻肝细胞膜的脂质过氧化反应及其肝脏炎症,调控免疫反应的NF-κB通路,具有保护肝细胞的作用。     

肝脾调补方对大鼠急性酒精性肝损伤的防护作用研究

目的：观察中药肝脾调补方对大鼠急性酒精性肝损伤的防护作用.方法：采用白酒灌胃法建立大鼠急性酒精性肝损伤模型.通过肝脾调补方高、中、低剂量灌胃,观察肝脾调补方对各组大鼠血清ALT、AST、肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）及肝组织匀浆超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、一氧化氮（NO）水平的影响.结果：肝脾调补方可明显降低大鼠血清ALT、AST、TNF-α、IL-6水平;降低肝组织匀浆的NO的含量,提高肝匀浆SOD、GSH-Px活性.结论：肝脾调补方对急性酒精性大鼠肝损伤有防护作用,能改善肝功能,其机制可能与减轻肝脏炎症、抗脂质过氧化有关.     

血府逐瘀汤对刀豆蛋白A诱导小鼠肝纤维化的干预作用

目的：观察血府逐瘀汤对刀豆蛋白A （ Con A）诱导小鼠肝纤维化的干预作用。方法： Balb/c雄性小鼠40只,随机分为正常组（8只）,模型组（16只）和治疗组（16只）。模型组和治疗组按照1.25mg/100g小鼠体重予以尾静脉注射Con A,正常组予注射相应剂量生理盐水,1次/周,共10周。治疗组于造模同时,予血府逐瘀汤药液1ml/100g小鼠体重灌胃,正常组及模型组则予以等量饮用水,1次/d。10周后,处理各组小鼠,留取血清、肝脾标本。全自动生化仪检测血清血清丙氨酸氨基转移酶（ALT）、门冬氨酸氨基转移酶（AST）和白蛋白（Alb）; HE和天狼星红染色观察肝组织炎症和胶原沉积; RT-PCR和Western Blot法检测肝组织α-平滑肌肌动蛋白（α-SMA）和转化生长因子β1（TGF-β1）表达。结果：模型组小鼠ALT和AST活性均较正常组明显升高（P＜0.05）;肝组织HE染色可见肝细胞坏死和大量炎性细胞浸润;天狼猩红染色可见大量胶原沉积和假小叶形成;肝组织α-SMA和TGF-β1较正常组显著升高（P＜0.01）。与模型组相比,治疗组ALT、 AST水平明显降低（P＜0.05）;肝脏炎症和胶原沉积明显改善;α-SMA和TGF-β1表达显著下调（P＜0.01）。结论：血府逐瘀汤可通过减轻肝脏炎症和抑制肝星状细胞活化而改善Con A诱导的小鼠肝纤维化。     

年龄与性别对异硫氰酸萘酯中毒小鼠急性肝损伤的影响

目的：研究年龄与性别对异硫氰酸萘酯（ANIT）中毒所致小鼠急性肝损伤的影响。方法：采用一次性ANIT 75mg/Kg经口灌胃染毒致5、10、20周龄雌雄性小鼠急性肝损伤,通过肝功能（ALT,AST、DBil）检测和肝组织HE染色病理学检查,观察不同性别和年龄小鼠急性肝损伤变化特征。结果：ANIT 75mg/Kg经口灌胃染毒可致5周龄小鼠血清ALT、AST和DBil明显上升,肝组织学呈明显淤胆改变。随着年龄增加,ANIT中毒所致小鼠上述改变更加明显。雄性小鼠明显重于雌性小鼠,雌性小鼠怀孕后肝损伤胆红素上升,ANIT 100mg/Kg经口灌胃可致雄性老年小鼠出现死亡。结论：ANIT中毒所致小鼠急性肝损伤与年龄和性别密切相关,毒性以雄性老年小鼠更加明显,只适合用于制作原发性硬化性胆管炎（PSC）动物模型。     

松果菊苷对大鼠急性肝损伤的保护作用

目的 研究松果菊苷对大鼠急性肝损伤的保护作用及机制.方法 随机将大鼠分为急性肝损伤组、药物干预组和正常对照组.大鼠经腹腔注射四氯化碳制备急性肝损伤模型;药物干预组大鼠给予松果菊苷连续灌胃7d,然后再进行四氯化碳染毒.染毒24h后测定各组大鼠血清ALT、AST水平,肝组织MDA浓度和SOD活性以及肝组织caspase-3活性和TNF-α水平;HE染色观察肝组织病理形态学改变.结果 急性肝损伤组大鼠血清ALT、AST水平以及组织MDA含量显著升高,伴SOD活性明显下降,与正常对照组相比差异非常显著;同时肝组织caspase-3活性和TNF-α水平亦显著高于对照组.预先给予松果菊苷能显著改善大鼠肝损伤,降低血清ALT、AST、MDA和caspase-3、TNF-α水平,并升高组织SOD活性.结论 松果菊苷对大鼠急性肝损伤有明显保护作用,机制可能与其抗氧化效应和清除自由基的作用有关.     

苍菊清肝降脂方对蛋氨酸-胆碱缺乏诱导小鼠脂肪性肝炎的防护作用

目的:观察苍菊清肝降脂方对蛋氨酸-胆碱缺乏(MCD)诱导的小鼠脂肪性肝炎的防护作用。方法:C57BL/6小鼠60只,雌雄各半,随机分为对照组、模型组、苍菊清肝降脂方(苍菊方)高中低剂量组和多稀磷脂酰胆碱组,对照组小鼠给予蛋氨酸-胆碱充足(MCS)饲料,其他各组小鼠予MCD饲料,自由进食。对照组和模型组灌胃饮用水,其余各组分别灌胃相应治疗药物。2w末,采集小鼠血清、肝组织标本,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、肝组织甘油三酯(TG)含量,观察肝组织HE染色及油红O染色。结果:与对照组小鼠比较,模型组小鼠ALT、AST、TG水平显著升高,经苍菊方干预的各组小鼠ALT、AST、TG水平均显著下降,且呈剂量依赖方式,其中高剂量苍菊方治疗疗效与多烯磷脂酰碱疗效组相近。模型组小鼠肝组织HE染色可见大量大泡性脂肪,肝细胞呈气球样变,油红O染色可见大量大小不等红色脂滴,部分融合成片,经用药干预,各组小鼠肝组织脂肪变性和肝脏炎症均明显改善。结论:苍菊清肝降脂方可明显改善MCD饮食诱导的脂肪性肝炎肝损伤程度。     

柳叶蜡梅提取物对小鼠急性酒精性肝损伤的保护作用

目的：研究柳叶蜡梅提取物对小鼠急性酒精性肝损伤是否具有保护作用。方法雄性C57BL/6小鼠分为4组,每组10只。对照组为正常C57BL/6小鼠;模型组用75％酒精溶液（8 mL/kg）灌胃,每天一次,连续4 d ,建立急性酒精性肝损伤模型;柳叶蜡梅组用柳叶蜡梅提取物（12 g/kg ）溶于生理盐水后灌胃,每天两次,连续11 d;实验组先按柳叶蜡梅组方法灌胃11 d ,同时在最后4 d按模型组方法建立急性酒精性肝损伤模型。通过比较各组血清ALT和AST水平,并评价肝组织病理损伤程度,观察柳叶蜡梅提取物对小鼠急性酒精性肝损伤的保护作用。结果柳叶蜡梅提取物可明显减轻酒精所致急性肝损伤,实验组小鼠血清ALT[（148．75±13．30） U/L]、AST [（170．75±16．96） U/L]与模型组ALT[（260．75±27．35） U/L]、AST[（337．75±37．68） U/L]相比明显降低,肝组织病理损伤和炎症反应减轻（P＜0．05）。结论柳叶蜡梅提取物在小鼠急性酒精性肝损伤中起到保护作用,可能成为急性酒精性肝损伤的新的治疗策略。     

三种品系小鼠对伴刀豆球蛋白A所致急性肝损伤的耐受性比较研究

目的：应用不同剂量伴刀豆球蛋白 A（ConA）诱导三种不同品系小鼠急性肝损伤,比较肝酶变化、死亡率和肝组织病理学变化。方法分别用6、12、20和30 mg·kg-1 ConA 处理 C57BL/6J、BABL/c 和 KM 小鼠,8 h 后对比观察急性肝损伤动物血清酶学及肝组织病理学变化情况。结果在6 mg·kg-1 ConA 的作用下,三个品系小鼠均被成功制造出急性肝损伤模型;在12 mg·kg-1 ConA 作用下,KM 小鼠血清 ALT 和AST 分别为（1006.8±12.1） U/L 和（1391.8±13.4）U/L,显著高于 BABL/c 小鼠[（75.7±0.5）U/L 和（284.7±23.4） U/L）和 C57BL/6J 小鼠（104.4±32.2）U/L 和（492.2±12.3）U/L,P 均〈0.05];同样,KM 小鼠肝指数和脾指数分别为（5.4±0.3）和（0.7±0.5）,均显著高于 BABL/c 小鼠[（5.2±0.4）和（0.6±0.3）和 C57BL/6J 小鼠（5.0±0.6）和（0.6±0.2）,P 均〈0.05];在20 mg·kg-1 ConA 作用下,三组小鼠血清 AST 和 ALT 水平无统计学差异,但 BABL/c 小鼠（4/10）和 C57BL/6J 小鼠（5/10）死亡率显著高于 KM 小鼠（1/10）;在30 mg·kg-1 ConA 作用下,三个品系小鼠死亡率均较高（KM 小鼠为30%,BABL/c 和C57BL/6J 小鼠均为100%）。结论不同品系的小鼠对 ConA 的耐受性不同,KM 小鼠对 ConA 的耐受性明显优于BABL/c 小鼠和 C57BL/6J 小鼠,且呈剂量依赖性。     

Fucoidan prevents concanavalin A-induced liver injury through induction of endogenous IL-10 in mice.

Fucoidan is a complex of sulfated polysaccharides derived from non-mammalian origin such as marine brown algae and induces cytokine expression. We investigated the effect of fucoidan on concanavalin A (Con A)-induced liver injury in mice. Liver injury was induced by an intravenous injection of Con A (18.5mg/kg). Various doses of fucoidan (1-30mg/kg) were intravenously administered 30min before Con A injection. The plasma alanine aminotransferase (ALT) and several cytokines levels were determined, and hepatic histological changes were also assessed. The effect of fucoidan administration by itself on induction of interleukin (IL)-10 in plasma and liver tissue was investigated. Con A administration induced an elevation of plasma ALT level, and fucoidan administration dose-dependently prevented the Con A-induced elevation of plasma ALT. Con A administration increased plasma TNF-alpha and IFN-gamma levels, and fucoidan pretreatment significantly inhibited these alterations and increased plasma IL-10 level. The inhibitory effect of fucoidan on Con A-induced liver injury and production of proinflammatory cytokines were reversed by anti-mouse IL-10 antibody pretreatment. Fucoidan induced the IL-10 production in plasma and liver tissue. These findings suggest that fucoidan prevents Con A-induced liver injury by mediating the endogenous IL-10 production and the inhibition of proinflammatory cytokine in mice.     

内毒素预适应减轻急性肝功能衰竭中热休克蛋白27的作用

目的研究热休克蛋白27（HSP27）介导内毒素（LPS）预适应减轻急性肝功能衰竭（ALF）的作用机制。方法实验动物为雄性C57BL/6小鼠。将小鼠分为5组,对照组为正常C57BL/6小鼠;肝功能衰竭组小鼠以LPS10μg/kg＋D-半乳糖胺700 mg/kg,用1 mL0.9%氯化钠溶液溶解后腹腔内注射,建立急性肝功能衰竭的模型;LPS预处理组小鼠经LPS预适应24 h后,建立急性肝功能衰竭的模型;HSP27干扰组小鼠和转染对照组小鼠分别以尾静脉注射包装有干扰HSP27表达的短发夹RNA的重组腺病毒以及对照空病毒,成功干扰HSP27表达后,经LPS预处理,建立急性肝功能衰竭模型。通过比较各组ALT和AST水平,评价肝组织病理损伤程度,以及检测肝组织内TNF-α、IL-6mRNA水平,观察HSP27对LPS预适应减轻急性肝功能衰竭的影响。结果 LPS预适应可明显减轻Galn/LPS所致的肝损伤,干扰HSP27的表达后,小鼠血清ALT和AST明显升高,肝组织病理损伤和炎性反应加重（P〈0.05）。下调HSP27的表达水平后,LPS预适应的保护作用几乎完全消失。结论 LPS预适应可以减轻小鼠的急性肝损伤,HSP27在这一效应中发挥重要作用。     

Effect of diphenyl dimethyl bicarboxylate on concanavalin A-induced liver injury in mice.

Diphenyl dimethyl bicarboxylate (DDB) is a hepatoprotectant and used in the treatment of chronic viral hepatitis patients in China. The aim of the present paper was to investigate the effect of DDB on liver injury mediated by immune response in concanavalin A (Con A)-treated mice. A dose of Con A 30 mg/kg was injected via the tailvein to induce liver injury in mice. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL) and tumor necrosis factor alpha (TNF-alpha) level as well as liver TNF-alpha mRNA expression were determined. The following results were obtained: (1) Prior oral administration of DDB 150 mg/kg markedly reduced the elevated serum ALT, TBA and TBIL levels, and the liver lesions in Con A-treated mice; (2) DDB significantly inhibited the elevation of serum TNF-alpha and liver TNF-alpha mRNA expression 2 h after Con A injection; (3) DDB significantly inhibited hepatocyte nuclear DNA fragmentation 12 h after Con A injection; (4) DDB dose-dependently prevented the direct DNA damage induced by CuSO(4)-Phen-Vit C-H(2)O(2) system in vitro, and the ex vivo experiment also showed that the administration of DDB reduced the susceptibility of mouse liver nuclei DNA to CuSO(4)-Phen-Vit C-H(2)O(2) system. These results suggest that DDB could directly protect hepatocyte DNA from oxidative damage, and inhibit TNF-alpha mRNA expression in liver tissue, which resulted in prevention of liver damage induced by Con A in mice.     

Macrophage inflammatory protein-1alpha plays a crucial role in concanavalin A-induced liver injury through induction of proinflammatory cytokines in mice.

BACKGROUND/AIMS:: The chemokines play roles in the development of immune mediated liver diseases. In this study, we investigate the involvement of macrophage inflammatory protein-1alpha (MIP-1alpha), one of the CC chemokines in concanavalin A (Con A)-induced liver injury in mice. METHODS:: Liver injury was induced by intravenous injection of Con A. Anti-mouse MIP-1alpha antibody, recombinant murine-MIP-1alpha and gadolinium chloride (GdCl(3)) were administrated prior to Con A injection. Plasma alanine aminotransferase (ALT), MIP-1alpha, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) levels were determined and histological assessment of the liver was performed. RESULTS:: Plasma MIP-1alpha level was elevated after Con A injection. The elevated plasma ALT level, mortality rate and histological change after Con A injection were inhibited by anti-MIP-1alpha antibody pretreatment. The elevated plasma ALT level after Con A injection was further enhanced by recombinant murine-MIP-1alpha. The elevated plasma TNF-alpha and IFN-gamma levels after Con A injection were inhibited by anti-MIP-1alpha antibody, and enhanced by recombinant murine-MIP-1alpha. GdCl(3) pretreatment inhibited the elevated plasma MIP-1alpha and ALT levels. CONCLUSIONS:: These findings suggest that MIP-1alpha is produced from Kupffer cells after Con A injection, and this CC chemokine plays a crucial role in Con A-induced liver injury through induction of proinflammatory cytokines.     

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。     

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorates concanavalin A-induced liver injury in mice.

BACKGROUND/AIMS: Prostacyclin (PGI(2)) is a potent mediator in the inflammatory and coagulation processes. The aim of this study was to test whether beraprost sodium, a PGI(2) analogue, could prevent experimental hepatic injury induced by concanavalin A (Con A), which is a model of fulminant hepatic failure. METHODS: Beraprost (100 microg/kg) was administered intraperitoneally simultaneously with Con A (40 mg/kg) in C57B6J mice. Blood circulation in the liver was determined by laser-Doppler flowmetry. Plasma levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-6 were determined. Levels of TNF-alpha and IFN-gamma in culture supernatant of splenocytes were also determined. RESULTS: Beraprost administration reduced the incidence of death following hepatic failure (76.5% vs. 29.4%, P<0.05). Plasma levels of ALT were significantly lower in the beraprost-treated group than in the control group, and in the former, there was concomitant suppression of the histological features of injury. Beraprost significantly increased hepatic blood flow volume in Con A-treated mice. Plasma levels of TNF-alpha and IFN-gamma were significantly reduced at 6 and 12 h after Con A injection, respectively, but the levels of IL-6 were increased at 6 h. In vitro, beraprost also suppressed Con A-induced TNF-alpha production in splenocytes, while it stimulated IFN-gamma production. CONCLUSION: These findings imply that beraprost suppresses Con A-induced liver injury. These data also suggest that beraprost, which is clinically effective in treating pulmonary hypertension, may have therapeutic potential for preventing hepatic injury.