禹州漏芦醇提物对四氯化碳所致小鼠急性肝损伤的影响

探讨禹州漏芦乙醇提取物对四氯化碳(CCl4)诱导小鼠急性肝损伤的保护作用。以CCl4诱导小鼠急性肝损伤模型,检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,同时测定肝匀浆中的超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)的水平。将肝大叶HE染色,观察各组小鼠的肝组织病理改变。结果表明,同模型组比较,禹州漏芦乙醇提取物各剂量组均能降低小鼠血清中ALT、AST及MDA活性,升高肝组织中GSH-Px和SOD的活性,并能明显改善肝组织的病理学损伤。禹州漏芦乙醇提取物对CCl4所致小鼠急性肝损伤具有较好保肝作用,其作用可能与清除体内自由基和抗氧化的作用有关。     

灰树花胞外多糖对四氯化碳致小鼠肝损伤的保护作用

四氯化碳可导致小鼠急性肝损伤,采用灰树花胞外多糖(GFP)防治后,对其血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和过氧化氢酶活力(CAT)以及肝组织匀浆中的丙二醛(MDA)和乳酸脱氢酶(LDH)进行测定,与模型组相比较,灰树花胞外多糖治疗组ALT、AST、MDA、LDH活力明显降低,而CAT活力明显升高。通过组织切片染色可以直观的看出灰树花胞外多糖能显著减轻肝组织病理变化程度。结果显示GFP对CCL4致小鼠急性肝损伤具有保护作用。     

育阴软肝中药对实验性肝损伤的保护作用

目的:研究育阴软肝方对小鼠化学性急性肝损伤的保护作用。方法:将55只昆明小鼠随机分为正常对照组、模型对照组、育阴软肝方低、中、高剂量组(n=11),连续给药7 d后,采用腹腔分别注射D-半乳糖胺(DGal N)、四氯化碳(CCl4)或硫代乙酰胺(TAA)复制三种肝损伤模型,通过测定血液生化指标、肝组织抗氧化酶及氧化产物的水平,研究育阴软肝方对实验性肝损伤的保护作用。结果:育阴软肝方能降低D-Gal N、CCl4或TAA诱发急性肝损伤小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)的水平,提高急性肝损伤小鼠肝组织超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性,降低丙二醛(MDA)的含量。其降酶保肝、抗氧化作用显示出一定的量效关系。结论:育阴软肝方对实验性急性肝损伤具有一定的保护作用。     

小鼠骨骼肌电转移hPON1 Q基因可以减轻CCl4诱导的急性肝损伤

目的 研究人Q型对氧磷酶1（human paraoxonase 1 Q,hPON1Q）转基因表达对小鼠四氯化碳（carbon tetrachloride,CCl4）诱导急性肝损伤的缓解效果,为防治肝脏疾病寻找新的途径.方法 小鼠骨骼肌直接注射含hPON1Q的真核表达质粒裸DNA并用电刺激介导表达,测量血清芳香酯酶的活性变化显示hPON1Q转基因表达效果,并使用血清谷丙转氨酶（ALT）、谷草转氨酶（AST）为指标及肝组织病理切片检测肝损伤的程度.结果 hPON1Q转基因表达小鼠血清中芳香酯酶活性提高约50%,并可持续到16 d以后.使用PON1裸DNA电刺激治疗组比对照组小鼠在用CCl4诱导24 h后血清芳香酯酶活性高60%,两种血清转氨酶指标及肝组织切片的病理学分析表明肝脏损伤程度有明显的减轻.结论 电刺激介导的重组人PON1Q基因裸DNA在小鼠体内的表达对CCl4诱导的肝损伤具有显著的防护作用.     

铁棍山药多糖对四氯化碳诱导的急性小鼠肝损伤的保护作用

为了研究铁棍山药(D.oppositacv.Tiegun)多糖对四氯化碳诱导的小鼠急性肝损伤的保护作用,取72只昆明小鼠随机分为对照组,四氯化碳(CCl4)模型组,阳性对照(联苯双酯)组,铁棍山药多糖低、中、高剂量组,每组12只,灌胃处理后使用CCl4制备急性肝损伤小鼠模型,观察各组形态学变化,同时测定生化指标。实验结果显示,经铁棍山药多糖处理的小鼠的肝损伤程度明显轻于模型组,铁棍山药多糖能降低小鼠血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)含量,提高超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性,降低丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)的含量。本研究结果表明,铁棍山药多糖对CCl4所诱导的小鼠肝损伤起到一定的保护作用。     

黄芪多糖与枸杞多糖联用对小鼠肝组织损伤的保护作用

探究黄芪多糖与枸杞多糖对四氯化碳(CCl_4)所致小鼠急性肝损伤的协同保护作用。采用CCl_4诱导小鼠急性肝损伤,动物处死后取血液测定血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,取肝脏计算肝指数并制备肝匀浆测定其中谷胱甘肽(GSH)活力、丙二醛(MDA)含量,并对小鼠肝脏进行组织切片观察,评价黄芪多糖与枸杞多糖联用对小鼠肝组织的保护效果。实验显示,黄芪多糖与枸杞多糖各配比(LBP 50 mg/kg+APS 100,LBP 70 mg/kg+APS 400,LBP 350 mg/kg+APS 800)均能显著抑制CCl_4急性肝损伤所引起的MDA含量、肝脏指数、ALT和AST活性的升高(p0.05),有效地提高肝脏中GSH的含量,减轻小鼠的肝组织损伤程度。本研究表明黄芪多糖与枸杞多糖联用对CCl_4诱导的小鼠急性肝损伤有明显的保护作用。     

紫堇灵对四氯化碳致小鼠急性肝损伤的保护作用及机制的研究

探讨紫堇灵(Corynoline,COR)对四氯化碳致小鼠急性肝损伤的保护作用及其机制。50只昆明种小鼠随机均分成5组,分别为正常组(Con)、GW9662阻断剂组(GW)、模型组(CCl4)、紫堇灵预处理组(COR)以及紫堇灵与阻断剂GW9662联合处理组(COR+GW),采用腹腔注射0.2%四氯化碳(CCl4)玉米油溶液(10 m L/kg)建造小鼠急性肝损伤模型。20 h后,小鼠脱臼处死后取血清,使用ELISA法检测血液中谷丙转氨酶(ALT)和谷草转氨酶(AST)活性。检测肝脏组织中C反应蛋白(CRP)的含量和肿瘤坏死因子α(TNF-α)的含量。利用HE染色观察肝组织病理学变化,通过Western blot方法检测肝脏组织中过氧化物酶增殖物激活受体γ(PPAR-γ)和NF-κB的蛋白表达。结果显示,紫堇灵能显著降低CCl4性肝损伤所引起的血清中ALT、AST活性升高,明显改善肝组织病理损伤程度;抑制肝脏中炎症因子CRP和TNF-ɑ含量和NF-κB蛋白表达量的升高;有效地拮抗受损肝脏组织中过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR-γ)蛋白表达量的降低。并且我们发现紫堇灵的这种减轻CCl4性肝损伤的作用几乎全部被GW9662阻断。COR对四氯化碳致小鼠急性肝损伤有一定的保护作用,其机制可能与PPAR-γ和NF-κB信号通路有关。     

水飞蓟素对四氯化碳致小鼠肝损伤的保护作用

目的:探讨水飞蓟素对四氯化碳致(CCl4)小鼠肝损伤是否有保护作用。方法:60只ICR小鼠随机分为6组(n=10),正常组、模型组、联苯双酯阳性对照组,低、中、高剂量水飞蓟素组(100、200、400 mg/kg)。各组连续给药10 d,末次给药1 h后,正常组腹腔注射橄榄油,其余各组腹腔注射0.12%的CCl4橄榄油溶液,16 h后测定血清中丙氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST),肝浆中丙二醛(MDA),谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)的水平。结果:水飞蓟素各剂量组能显著的抑制肝损伤血清中ALT和AST的升高(P<0.05,P<0.01),亦能抑制肝组织中MDA的升高(P<0.01),增加肝组织中SOD的活性和GSH-Px的水平(P<0.05)。结论:水飞蓟素具有明显的四氯化碳致小鼠肝损伤的保护作用。     

茵栀黄注射液对四氯化碳和硫化乙酰胺致小鼠肝脏损伤的保护作用

目的：研究茵栀黄注射液对四氯化碳（CCl4)和硫代乙酰胺（TAA）所致小鼠肝脏损伤的保护作用。方法：采用四氯化碳和硫代乙酰胺造成小鼠化学性损伤,观察茵栀黄注射液的保护作用,结果：小鼠静脉注射茵栀黄注射液能明显降低CCl4和TAA所致小鼠血清ALT和AST水平,并可显著改善小鼠肝损伤的病变程度,结论：茵栀黄注射液对CCl4和TAA所致小鼠肝损伤具有保护作用。     

荷叶总生物碱激活肝脏AMPK/Nrf2通路缓解对乙酰氨基酚诱导的小鼠急性肝损伤

为探讨荷叶总生物碱(TAL)对对乙酰氨基酚(APAP)所致小鼠急性肝损伤的保护作用及可能机制,小鼠被随机分为正常组,模型组和TAL低、高剂量组(30、100 mg/kg),连续灌胃给药七天后,除正常组外,其余各组腹腔注射300 mg/kg的APAP诱导急性肝损伤。12小时后,收集各组小鼠的血清与肝脏样本,进行后续实验。结果显示,与模型组相比,TAL可显著降低血清中的ALT和AST活性,下调肝组织中TNF-α、IL-1β、IL-6和MDA含量,上调肝组织中SOD、CAT、GSH-Px和GSH的水平。此外,TAL还明显改善了APAP诱导的小鼠肝组织病变。在TAL的作用下,肝内AMPK磷酸化水平提高,Nrf2蛋白入核,HO-1和GCLC基因表达上调。综上所述,TAL对APAP诱导的急性肝损伤具有保护作用,其机制可能与激活AMPK/Nrf2通路相关。     

虫草素对四氯化碳所致小鼠急性肝损伤的保护作用

本文探究蛹虫草活性成分虫草素对四氯化碳（CCl₄）造成的小鼠急性肝损伤的保护作用及其分子机制。首先建立四氯化碳致小鼠急性肝损伤的动物模型,通过检测血清生化指标、肝功指标的变化及HE染色观察组织切片病理的病变情况,评价虫草素的保肝效果,进一步通过Western blot检测虫草素能否通过激活Nrf-2/Keap1信号通路及其下游抗氧化因子（HO-1、NQO-1）的表达来提高机体抗氧化损伤能力以及抑制炎症因子（TNFα、TNFβ、IL-6、IL-10）的表达。对比模型组结果显示,虫草素能极显著降低（P<0.01）小鼠血清中ALT、AST及肝脏中MDA水平,并能极显著提高肝脏中SOD水平（P<0.01）;HE染色结果显示虫草素能有效降低改善受损肝组织中的炎细胞浸润及纤维组织增生;Western blot结果表明虫草素能够通过激活Nrf-2信号通路,促进下游抗氧化因子及抗炎因子的表达,从而降低炎症反应。虫草素对CCl₄致小鼠急性肝损伤具有一定的保护作用,其机制与Nrf-2信号通路相关,实验结果为后续蛹虫草及虫草素的开发应用奠定基础。     

Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.     

Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1β in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.     

聚乙二醇修饰重组细胞珠蛋白对小鼠急性肝损伤的保护作用

旨在探究聚乙二醇修饰重组细胞珠蛋白(PEG modified recombinant cytoglobin,PEG-rCygb)对小鼠急性肝损伤的保护作用。采用CCl4诱导KM小鼠急性肝损伤模型,尾静脉注射PEG-rCygb,收集血清及肝脏组织检测各项生化指标及组织病理学变化。结果表明,PEG-rCygb治疗组小鼠肝脏系数减小,血清中AST﹑ALT水平降低,肝组织匀浆中MDA含量减少,GSH含量增加,T-SOD、CAT活性升高。肝组织切片HE染色显示PEG-rCygb可以缓解肝细胞脂肪变性,减少炎症因子,减轻肝细胞损伤。体外细胞学实验表明rCygb经PEG修饰后对H2O2造成的肝星状细胞(HSC)氧化损伤发挥的保护作用增强。研究结果显示PEG-rCygb提高了机体对自由基的清除能力,对CCl4引起的小鼠急性肝损伤具有保护作用。     

Early growth response (EGR)-1 is required for timely cell-cycle entry and progression in hepatocytes after acute carbon tetrachloride exposure in mice

Cell-cycle induction in hepatocytes protects from prolonged tissue damage after toxic liver injury. Early growth response (Egr)-1(-/-) mice exhibit increased liver injury after carbon tetrachloride (CCl(4)) exposure and reduced TNF-α production. Because TNF-α is required for prompt cell-cycle induction after liver injury, here, we tested the hypothesis that Egr-1 is required for timely hepatocyte entry into the cell cycle after CCl(4)-induced liver injury. Acute liver injury was induced by a single injection of CCl(4). Assays were employed to assess indices of the cell cycle in liver after CCl(4) exposure. Bromodeoxyuridine incorporation peaked in wild-type mice at 48 h after CCl(4) but was reduced by 80% in Egr-1(-/-) mice. Proliferating-cell nuclear-antigen immunohistochemistry revealed blocks in cell-cycle entry and progression to DNA synthesis in Egr-1-deficient mice 48 h after CCl(4). Cyclin D, important for G0/G1 progression, was reduced at baseline and 36 h after CCl(4). Cyclin E1, required for G1/S-phase transition, was reduced in Egr-1(-/-) mice 24 and 48 h after CCl(4) exposure and was associated with reduced phosphorylation of the retinoblastoma protein. Proliferation in Egr-1(-/-) mice was delayed, rather than blocked, because indices of cell-cycle progression were restored 72 h after CCl(4) exposure. We concluded that Egr-1 was required for prompt cell-cycle entry (G0- to G1-phase) and G1/S-phase transition after toxic liver injury. These data support the hypothesis that Egr-1 provides hepatoprotection in the CCl(4)-injured liver, attributable, in part, to timely cell-cycle induction and progression.     

冬虫夏草菌丝提取物对化学性肝损伤的辅助保护作用

为明确冬虫夏草菌丝提取物对急性肝损伤小鼠谷丙转氨酶（ALT）、谷草转氨酶（AST）、肝细胞变性及坏死程度的影响,采用四氯化碳（CCl4）诱导小鼠急性化学性肝损伤模型,将动物随机分成5组,分别是空白对照组、模型组、冬虫夏草菌丝提取物低剂量组（1.11g/kg BW）、中剂量组（3.33g/kg BW）、高剂量组（10.00g/kg BW）,检测血清ALT、AST值,并取肝脏作病理切片,观察肝脏的病理损伤情况。冬虫夏草菌丝提取物高剂量组能明显降低CCl4急性肝损伤小鼠血清ALT值,减轻肝细胞坏死程度,表明冬虫夏草菌丝提取物对化学性肝损伤有辅助保护功能。     

Protective effect of gossypitrin on carbon tetrachloride-induced in vivo hepatotoxicity

Carbon tetrachloride (CCl4) is a known environmental biohazard, which induces lipid peroxidation (LPO) and oxidative damage in rat liver. In this study, the hepatoprotective effect of Gossypitrin, a flavonoid extracted from Hibiscus elatus S.W, was investigated against the CCl4-induced in vivo hepatotoxicity. The levels of malondialdehyde (MDA) were assayed as an index of LPO and the levels of catalase (CAT) activity as a biomarker of oxidative damage. Leakage of aspartate aminotransferase (ALT) and lactate dehydrogenase (LDH), liver weight/body weight ratio as well as morphological parameters were used as signs of hepatotoxicity. CCl4 (1 ml/kg), intraperitoneally injected into rats, caused increased MDA production and CAT activity, and also a significant ALT and LDH leakage as compared to levels of these constituents in the control group. Changes in morphology, including steatosis, cells forming balloon cells and necrosis were evaluated in the hepatotoxin-induced damage. Treatment of rats with Gossypitrin (3.98, 5.97 and 8.95 mg/kg) 2 h before and 2 h after CCl4 injection, protected hepatocytes against cell injury induced by CCl4 and its efficacy as an antioxidant was similar to vitamin E (used as a reference antioxidant). These results are consistent with the conclusion that the toxicity of CCl4 is due to LPO and the generation of reactive oxygen species (ROS), and that Gossypitrin's protective effects relate to its direct radical scavenging ability and other antioxidative processes induced by its structure.     

蟛蜞菊内酯对四氯化碳致小鼠肝损伤的保护作用

目的:研究中药活性物质蟛蜞菊内酯的保肝作用及其机制。方法:采用小鼠腹腔注射CCl4制作肝损伤模型,测定小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、丙二醛(MDA),谷胱甘肽(GSH)和超氧化物歧化酶(SOD)指标,进行肝脏的组织病理学检查,观察蟛蜞菊内酯对CCl4所致肝损伤的保护作用。结果:蟛蜞菊内酯能明显降低肝损伤小鼠的血清ALT、AST和肝组织匀浆中MDA含量,SOD活力增强,明显减轻肝组织变性。结论蟛蜞菊内酯对CCl4引起的肝损伤有明显的保护作用,其机制可能与其抗氧化作用有关。