水红花子对小鼠免疫性肝损伤的影响

目的:观察人用口服剂量40倍的水红花子对免疫性肝损伤小鼠形态学、生理生化学方面的影响,为临床安全用药提供依据。方法:观察水红花子20g.kg-1.d-1对BCG/LPS致免疫性肝损伤模型小鼠肝脏病理变化及血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性,肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量的影响。结果:水红花子组免疫性肝损伤小鼠肝脏病理损伤明显,血清ALT、AST均显著升高(P<0.01),肝组织SOD值明显下降(P<0.05),MDA明显升高(P<0.05)。结论:人用口服剂量40倍的水红花子可提高免疫性肝损伤小鼠的肝脏损伤程度,具有肝毒性,临床不可长期过量服用。     

复方柴郁汤对小鼠免疫性肝损伤的影响

目的：观察中药复方柴郁汤对小鼠免疫性肝损伤的影响。方法：将72只小鼠随机分为空白组、病理组、日达仙组以及复方柴郁汤大、中、小剂量组，采用BCG＋LPS造模，观察并比较各组小鼠血清ALT、AST含量以及肝脏病理结构。结果：各治疗组和日达仙组的ALT、AST值明显低于病理组（P〈0．01），组织结构明显优于病理组（P〈0.01）。其中中剂量组又优于其他治疗组和对照组（P〈0．05）。结论：复方柴郁汤能明显降低免疫性肝损伤小鼠血清ALT、AST的活力单位．减轻其免疫性肝损伤程度。     

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。     

水飞蓟宾-磷脂酰胆碱复合物对氨基半乳糖胺与BCG＋LPS诱导的小鼠肝损伤的影响

目的：研究水飞蓟宾-磷脂酰胆碱复合物（silybin-phosphatidylcholine compound,SPC）对D-半乳糖胺（D-galactosamine,D-galN）和脂多糖（lipopolysaccharide,LPS）与卡介苗（Bacillus Calmette-Guerin Vaccine,BCG）诱导的小鼠肝损伤实验的影响.方法：将100只小鼠随机分成10组,分别用于SPC对D-galN和LPS＋BCG诱导的小鼠肝损伤影响实验.分别用D-galN和LPS＋BCG复制肝损伤动物模型,测定血清中ALT、AST和肝组织中TG水平并进行肝脏病理组织学检查.用200mg·Kg-1 SPC剂量对2种肝损伤小鼠进行处理,观察SPC对血清酶学及组织学改变的影响.结果：SPC不同程度的使D-galN和LPS＋ BCG诱导升高的ALT、AST和TG明显降低（p〈0.05）,并能减轻两种肝损伤动物模型肝脏组织学结构的改变.结论：SPC对D-galN和LPS＋BCG诱导的肝损伤具有明显的保护作用.     

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。     

金银花对四氯化碳所致小鼠急性肝损伤的影响

目的 研究金银花对四氯化碳所致小鼠急性肝损伤的保护作用.方法 采用四氯化碳腹腔注射诱导小鼠急性肝损伤模型,观察金银花对小鼠血清谷丙转氨酶(AST)、谷草转氨酶(AST)的活性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),肿瘤坏死因子(TNF-α)水平的影响.结果 金银花提取物能显著降低血清中ALT、AST水平(P<0.05或P<0.01),提高肝组织匀浆SOD、GSH-Px水平(P<0.05或P<0.01),减少TNF-α、MDA含量(P<0.05或P<0.01).结论 金银花提取物具有显著的保肝作用.     

紫球藻多糖对小鼠慢性肝损伤的保护作用

目的探讨紫球藻多糖对小鼠慢性肝损伤的保护作用。方法用四氯化碳导致小鼠慢性肝损伤,各组〔高:5.86 g/(kg.d),中:2.93 g/(kg.d),低:1.46 g/(kg.d)〕每日灌胃不同剂量紫球藻多糖,检测饲养5 w的小鼠血清的ALT、AST活力,肝组织的SOD活力和MDA、GSH含量,观察高、中、低剂量组血清ALT、AST活力以及肝组织的SOD活力和MDA、GSH含量的变化。结果紫球藻多糖能降低肝损小鼠ALT、AST活力(P<0.01),提高其肝组织SOD的活力、GSH含量并降低其MDA含量(P<0.01)。结论紫球藻多糖具有一定的保肝作用,但尚不能达到正常水平,作用机制可能与提高其抗氧化能力有关,且保肝程度并不随剂量的增加而持续显著增加。     

青蒿琥酯上调HO-1对老龄脓毒症小鼠急性肝损伤的作用

目的探讨青蒿琥酯能否上调血红素氧合酶-1(HO-1)起到对老龄脓毒症小鼠急性肝损伤的保护作用。方法采用盲肠结扎穿孔术(CLP)制备脓毒症小鼠模型,72只雄性昆明小白鼠按随机数字表法分为四组:假手术组(sham组)、脓毒症组(CLP组)、青蒿琥酯干预组(ART组)、HO-1抑制剂组(Zn PP组),各组按术后6 h、12 h、24 h分为3个亚组。分别于上述时间点处死小鼠,分时项检测各组血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),ELISA法检测血清肿瘤坏死因子-α(TNF-α),白介素-6(IL-6)水平变化,采用Western印迹法及免疫组化法检测24 h亚组肝组织HO-1表达水平,光学显微镜观察各组小鼠24 h亚组肝组织病理变化情况。结果与sham组相比,CLP组小鼠血清ALT、AST水平升高(P<0.05);血清TNF-α、IL-6水平升高(P<0.05);肝组织中HO-1水平表达升高(P<0.05);肝组织病理损伤明显。与CLP组相比,ART组血清ALT、AST水平显著下降(P<0.05);血清TNF-α、IL-6水平下降(P<0.05);肝组织HO-1水平表达明显升高(P<0.05);肝组织病理损伤程度减轻。Zn PP组与ART组相比,血清ALT、AST水平升高(P<0.05);血清TNF-α、IL-6水平升高(P<0.05);肝组织中HO-1表达水平下降(P<0.05);肝脏病理损伤明显。结论青蒿琥酯可以通过上调HO-1减轻老龄脓毒症小鼠急性肝损伤。     

鬼针草水提物对脂多糖诱导肝损伤小鼠肿瘤坏死因子-α、白细胞介素-6的影响

目的研究鬼针草水提物对脂多糖(LPS)诱导小鼠肝损伤的保护作用及对小鼠细胞因子的影响。方法一次性腹腔注射LPS(400μg/kg)建立小鼠化学性肝损伤模型,鬼针草水提物灌胃,测定血清谷丙转氨酶(ALT)、谷酰转肽酶(GGT)、肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的水平和肝匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的含量,肝组织HE染色作病理切片分析。结果鬼针草水提物可明显改善LPS引起的小鼠肝组织病理损伤,降低LPS致小鼠血浆ALT、GGT、TNF-α和IL-6的水平,GSH-Px活性明显增高,肝细胞水肿、变性等损伤程度明显减轻。结论鬼针草水提物能够明显降低急性肝损伤小鼠TNF-α、IL-6水平,减轻氧化应激损伤,具有较强的保肝作用。     

叶黄素对化学诱导急性肝损伤小鼠的预防研究

目的 研究叶黄素对四氯化碳(CCl4)所致急性化学性肝损伤小鼠的保护作用.方法 雄性昆明种小鼠60只,随机分为正常对照组、急性化学性肝损伤模型组(模型组)、联苯双酯阳性对照组(阳性对照组)(联苯双酯15 mg/kg)以及叶黄素低、中、高剂量组(10、15、20 mg/kg)共6组,每组10只.测定并比较各组小鼠肝脏系数,血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性与丙二醛(MDA)含量;测定肝组织中SOD、GSH-Px活性、MDA含量以及组织病理系数.结果 叶黄素各剂量组均能升高急性化学性肝损伤小鼠血清与肝组织SOD、GSH-Px活性(P＜0.01),降低血清ALT、AST活性(P＜0.01)和血清与肝组织MDA含量(P＜0.01),并能不同程度地改善肝脏病理组织损伤.结论 叶黄素对CCl4所致急性化学性肝损伤具有预防性保护作用.     

克肝胶囊对小鼠实验性急性肝损伤的影响

目的：观察克肝胶囊对实验性急性肝损伤的影响,方法：分别用ＣＣｌ４、Ｄ－ＧＬａＮ、ＡＮＩＴ制成肝损伤模型,运用克肝胶囊治疗,观察ＡＬＴ、ＡＳＴ、ＴＢｉｌ、肝脏指数及肝脏组织病理改变,以乙肝解毒胶囊作对照。结果：与乙肝解毒胶囊一样,克肝胶囊各剂量组都能显著降低ＡＬＴ、ＡＳＴ、ＴＢｉｌ,肝脏指数及改善肝脏病理（Ｐ〈０．０５－０．０１）,对某些指标的影响甚至优于乙肝解毒胶囊,结论克肝胶囊有抗急性４肝损伤的     

Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins

BACKGROUND/AIMS: Bacillus Calmette Guerin (BCG) infection causes hepatic injury following granuloma formation and secretion of cytokines which render mice highly sensitive to endotoxin-mediated hepatotoxicity. This work investigates the role of inducible nitric oxide synthase (iNOS) in liver damage induced by BCG and endotoxins in BCG-infected mice. METHODS: Liver injury and cytokine activation induced by BCG and by LPS upon BCG infection (BCG/LPS) were compared in wild-type and iNOS-/- mice. RESULTS: iNOS-/- mice infected with living BCG are protected from hepatic injury when compared to wild-type mice which express iNOS protein in macrophages forming hepatic granulomas. In addition, iNOS-/- mice show a decrease in BCG-induced IFN-gamma serum levels. LPS challenge in BCG-infected mice strongly activates iNOS in the liver and spleen of wild-type mice which show important liver damage associated with a dramatic increase in TNF and IL-6 and also Th1 type cytokines. In contrast, iNOS-/- mice are protected from liver injury after BCG/LPS challenge and their TNF, IL-6 and Th1 type cytokine serum levels raise moderately. CONCLUSIONS: These results demonstrate that nitric oxide (NO) from iNOS is involved in hepatotoxicity induced by both mycobacterial infection and endotoxin effects upon BCG infection and that inhibition of NO from iNOS protects from liver injuries.     

清热利湿法对小鼠CCl4急性肝损伤的保护作用

目的:观察清热利湿法对四氯化碳(CCl4)诱导的小鼠急性肝损伤的保护作用.方法:给小鼠以0.12?l4花生油溶液腹腔注射,制备急性化学性肝损伤模型,测定各组血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,计算肝脏指数,光镜下观察肝组织病理学变化.结果:小鼠灌胃给予清香散后,清香散大、小剂量组均能显著降低CCl4所致小鼠急性肝损伤血清ALT、AST活性及肝脏指数(P<0.05),大剂量组能明显改善肝组织损伤的程度,与模型组比较差异有统计学意义(P<0.05).小剂量组虽有改善肝组织损伤的趋势,但与模型组比较差异无统计学意义(P>0.05).结论:清热利湿法对CCl4诱导的小鼠急性肝损伤有保护作用.     

Hepatoprotective role of ganoderma lucidum polysaccharide against BCG—induced immune liver injury in mice

AIM：To examine the effect of ganoderma lucidum polysaccharide(GLP)on the immune liver injury induced by BCG infection,and investigate the relationship between degrees of hepatic damage and NO production in mice.METHODS:Immune hepatic injury was markedly induced by BCG-pretreatment(125mg&#183;kg^-1,2-week,iv)or by BCG-pretreatment plus lipopolysaccharide(LPS,125μg&#183;kg^-1,12-hour,iv)in mice in vivo.Hepatocellular damage induced by BCG-pretreated plus inflammatory cytokines mixture(CM).which was includid TNF-α,IL-1β,IFN-γand LPSin culture medium in vitro.Administration of GLP was performed by oral or incubating with culture medium at immune stimuli simultaneity.Liver damage was determined by activity of alaine aminotransferase(ALT)in serum and in hepatocytes cultured supernatant,by liver weight changes and histopathlogical examination.NO production in the cultured supernatant was determined by the Griess reaction.Moreover,inducible nitric oxide synthase(iNOS)protein expression was also examinated by immunohistochemical method.RESULTS:Immune hepatic injury was markedly induced by BCG or BCGplus inflammatory cytokines in BALB/c mice in vivoand in vito.Under BCG-stimulated condition,augment of the liver weight and increase of the serum/supernatant ALTlevel were observed,as well as granuloma forming and inflammatory cells soakage were observed by microscopic analysis within liver tissues.Moreover.NO production was also increased by BCGor/and CM stimuli in the culture supernatant ,and a lot of iNOS positive staining was observed in BCG-prestimulated hepatic sections.Applicatin of GLP significantly mitigated hepatic tunefaction,decreased ALT enzyme release and NO production in serum/supernatant,improved the pathological changes of chronic and acute inflammation induced by BCG-stimuli in mice.Moreover.the immunohistochemical result showed that GLP inhibited iNOS protein expression in BCG-immune hepatic damage model.CONCLUSION:The present study indicates that NO participates in immune liver injury in duced by Mycobacterium bovisBCG infection.The mechanisms of protective roles by GLPfor BCG-induced immune liver injury may be due to influence NO production in mice.     

大蒜油对对乙酰氨基酚所致小鼠急性肝损伤的保护作用

目的 观察大蒜油对对乙酰氨基酚(AP)所致小鼠急性肝损伤是否有保护作用.方法 将75只小鼠随机分为阴性对照组、模型组以及大蒜油低、中、高三个剂量组(分别为25、50、100 mg/kg),给药后2 h除阴性对照组其他各组小鼠均灌胃AP 240 mg/kg;24 h后小鼠摘眼球取血,离心,测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)的活性,同时比较各组小鼠的肝脏系数和肝脏病理组织学变化.结果 与模型组相比,大蒜油低、中、高剂量组的肝脏系数明显减小,血清ALT、AST活性显著降低(P＜0.01),同时肝脏组织病理学检查发现模型组肝细胞发生气球样变,甚至坏死,炎细胞浸润,而大蒜油组无明显病理学改变.结论 大蒜油对AP所致小鼠急性肝损伤有明显的保护作用.     

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.     

Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide

AIM: To investigate the effects and mechanisms of melatonin on immunological liver injury in mice.METHODS: A model of liver injury was induced by tail vein injecton of Bad#us Calmet~ Guenn (BCG) and lipopolysaccharide(LPS) in mice. Kupffer cells and hepatocytes were isolated and cultured according to a modified two-step collagenase perfusion technique. Levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST) and nitric oxide(NO), content of malondiadehyde (MDA), activity of superoxide dismutase (SOD), were measured by biochemical methods.Tumor necrosis factor-α (TNF-α) activity was determined by RIA. Interleukin (IL)-1 activity was measured by thymocyte proliferation bioassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a lightmicroscope.RESULTS: Immunological liver injury induced by BCG+LPS was successfully duplicated. Serum transaminase (ALT,AST) activities were significantly decreased by melatonin(0.25, 1.0, 4.0 mg/kg bm). Meanwhile, MDA content was decreased and SOD in liver homogenates was upregulated.Furthermore, pro-inflammatory mediators (TNF-α, IL-1, NO)in serum and liver homogenates were significantly reduced by melatonin. Histological examination demonstrated that melatonin could attenuate the area and extent of necrosis,reduce the immigration of inflammatory cells. In in vitro experiment, TNF-α was inhibited at the concentrations of 10^-8-10^-6 mol/L of melatonin, while IL-1 production of Kupffer cells induced by LPS (5 t~g/mL) was decreased only at the concentration of 10^-6 mol/L of melatonin, but no effect on NO production was observed. Immunological liver injury model in vitro was established by incubating hepatocytes with BCG- and LPS-induced Kupffer cells. Activities of ALT,TNF-α, IL-1, and MDA in supernatant were significantly increased. Melatonin had little effect on the level of ALT,but reduced the content of TNF-α and MDA at concentrations of 10^-7-10^-5 mol/L and decreased the content of IL-1 at concentrations of 10^-6-10^-5 mol/L.CONCLUSION: Melatonin could significantly protect liver injury in mice, which was related to free radical scavenging,increased SOD activity and pro-inflammatory mediators.