赶黄草水提取物利胆退黄作用的研究

目的探讨赶黄草水提取物的利胆退黄作用。方法采用胆管引流法，观察赶黄草水提取物对正常大鼠胆汁分泌量的影响：采用胆管结扎致大鼠梗阻性黄疸模型和α-萘异硫氰酸酯（ANIT）致胆汁淤积模型，观察赶黄草水提取物对模型大鼠血清总胆红素（TBIL）含量、碱性磷酸酶（ALP）活性、γ-谷氨酰转移酶（GGT）活性、门冬氨酸转氨酶（AST）活性、丙氨酸转氨酶（ALT）活性的影响。结果赶黄草水提取物能增加正常大鼠胆汁的分泌量，但对血清TBIL含量无影响；对于胆管结扎所致梗阻性黄疸模型大鼠和ANIT所致的胆汁淤积模型大鼠．赶黄草水提取物能显著降低血清TBIL含量，抑制血清ALP、GGT、AST和ALT活性。结论赶黄草水提取物具有明显的利胆退黄作用。     

天麻素对乙醇诱导肝细胞株L02细胞损伤的影响

目的:探讨天麻素对乙醇诱导肝细胞株L02损伤的影响。方法:将人肝细胞株L02培养,加入不同浓度的乙醇,采用MTT比色法确定乙醇作用的浓度。用流式细胞仪测定细胞活性氧簇(ROS)及线粒体膜电位的改变;采用反相高效液相色谱(RP-HPLC)分析法检测细胞ATP含量。结果:乙醇(25 mL/L)作用36 h可损伤肝细胞,细胞内ROS的水平明显增加;而细胞线粒体膜电位及肝细胞中ATP的含量则显著降低(P0.01)。天麻素具有减轻细胞损伤的作用,并可降低损伤的肝细胞内ROS的含量,增加细胞线粒体膜电位和ATP的水平。结论:天麻素可抑制乙醇诱导的肝细胞损伤及脂质过氧化反应,改善线粒体功能,增加能量合成,发挥保护肝细胞的作用。     

虎耳草素对长春新碱诱导的神经病理性疼痛的影响

目的:探讨虎耳草素对长春新碱诱导的神经病理性疼痛的影响及其作用机制。方法:利用长春新碱致神经病理性疼痛模型小鼠,腹腔注射虎耳草素100 mg/kg,通过行为学实验测试机械性缩足反射阈值;生化检测氧化应激相关指标丙二醛(MDA)和谷胱甘肽(GSH)的表达;ELISA检测炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素(IL)-1β的表达;原子吸收光谱检测钙离子浓度的变化。结果:虎耳草素能够显著地抑制长春新碱诱导的神经病理性疼痛(CNP)模型小鼠机械性痛觉过敏,且能改善CNP小鼠高氧化应激状态和降低CNP小鼠TNF-α、IL-1β的表达水平及钙离子浓度。结论:虎耳草素拮抗CNP,且该作用机制可能与其抑制氧化应激、降低炎症因子TNF-α、IL-1α的表达及钙离子浓度有关。     

圣草酚通过调节Nrf2通路促进氧化应激诱导的肝癌细胞的凋亡

目的:探究圣草酚对氧化应激诱导的肝癌细胞凋亡的作用机制.方法:CCK-8测定圣草酚对细胞的毒性.将Huh7细胞分为对照组、H2O2组、圣草酚组、H2O2+圣草酚组,分别用0.5 mmol/L H2O2或78 μmol/L圣草酚处理细胞48h;2,7-二氯荧光素双乙酸酯(DCFH-DA)探针测定ROS的含量;试剂盒检测S...     

TAK1对非酒精性脂肪肝小鼠的保护作用及其对巨噬细胞极化的影响

目的:探讨转化生长因子β激活激酶-1(TAK1)在非酒精性脂肪性肝病(NFALD)中的作用及其对巨噬细胞极化的影响。方法:将80只5~6周龄C57BL/6雄性小鼠随机分为对照组、模型组、低剂量组和高剂量组。其中,对照组小鼠给予正常饮食,模型组小鼠给予高脂饮食,低剂量和高剂量组小鼠在高脂饮食的基础上,每周腹腔注射1 mg/kg和5 mg/kg的TAK1抑制剂5Z-7-oxozeaenol。持续饲养12周后,HE染色评估肝脏形态。测量小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白(LDL-C)含量。流式细胞术检测小鼠肝脏组织巨噬细胞极化情况。RT-PCR法检测小鼠肝脏组织CD11c、CD206、IL-1β和IL-10 mRNA表达。ELISA检测小鼠肝脏组织IL-1β、IL-10、TNF-α和TGF-β1含量。结果:HE染色结果显示,对照组小鼠肝细胞排列整齐,无脂肪变性和炎症细胞浸润;模型组小鼠肝细胞内可见明显脂肪变性,NAFLD活动度积分显著升高(P<0.05);低剂量组和高剂量组小鼠脂肪变性和炎症细胞显著减少,NAFLD活动度积分明显降低(P<0.05)。与对照组相比,模型组小鼠血清ALT、AST、ALP、TC、TG和LDL-C含量均显著升高,HDL-C含量显著降低(P<0.05);与模型组相比,低剂量组和高剂量小鼠血清ALT、AST、ALP、TC、TG和LDL-C含量显著降低,HDL-C含量显著升高(P<0.05)。与对照组相比,模型组小鼠肝脏组织M1/M2、M1型巨噬细胞标志物CD11c和IL-1βmRNA均明显升高,M2型巨噬细胞标志物CD206和IL-10 mRNA表达降低(P<0.05);与模型组相比,低剂量和高剂量组小鼠肝脏组织M1/M2、CD11c和IL-1βmRNA表达均显著降低,CD206和IL-10 mRNA表达升高(P<0.05)。与对照组相比,模型组小鼠肝脏组织IL-1β和TNF-α表达明显升高,IL-10和TGF-β1表达明显降低(P<0.05);与模型组相比,低剂量和高剂量组小鼠肝脏组织IL-1β和TNF-α表达明显降低,IL-10和TGF-β1表达明显升高(P<0.05)。结论:TAK1抑制剂通过调控巨噬细胞极化,抑制肝脏炎症,发挥肝脏保护作用。     

异荭草苷对慢性阻塞性肺疾病模型大鼠的影响及机制

目的：探究异荭草苷对慢性阻塞性肺疾病（COPD）的作用及机制。方法：36只大鼠随机分为对照组、模型组、异荭草苷低、中、高剂量组和地塞米松组,除对照组外,其余组采用香烟烟雾暴露+脂多糖（LPS）法建立COPD大鼠模型,药物干预14 d后,称重计算肺指数,HE染色检测肺组织病理损伤,Smith评分法进行肺损伤评分,肺功能检测仪检测肺活量（FVC）、一秒用力呼气容积（FEV1）、一秒率（FEV1/FVC）,血气分析仪检测动脉氧分压（PaO2）、血氧饱和度（SaO2）、动脉二氧化碳分压（PaCO2）,ELISA检测肺组织炎症因子IL-6、TNF-α、IL-1β、IL-8水平,试剂盒检测肺组织氧化应激指标MDA和SOD含量,Western blot检测Toll-样受体4(TLR4)、髓样分化因子（MyD88）、核因子-κB p65(NF-κB p65)及p-NF-κB p65蛋白水平,并计算p-NF-κB p65/NF-κB p65。结果：与对照组比较,模型组肺组织出现炎症浸润,肺泡严重塌陷,肺泡壁增厚,肺间质水肿;与模型组比较,异荭草苷中、高剂量组和地塞米松组大鼠肺组织病理损伤明显改善,肺指数...     

葛花总黄酮通过调控Keap1-Nrf2/HO-1信号通路对糖尿病大鼠视网膜神经节细胞的保护作用

目的 探讨葛花总黄酮(total flavonoids of Pueraria lobate,TFF)对糖尿病大鼠视网膜神经节细胞(RGC)的影响及机制.方法 雄性SD大鼠60只,利用链脲佐菌素(STZ)诱导糖尿病模型.糖尿病大鼠随机分成三组:糖尿病组(DM)、TFF组(200 mg/kg)及二甲双胍组(Met,75 mg/kg,阳性对照)灌胃治疗,另取15只正常大鼠作为对照组(CON).12周后,检测各组大鼠血糖、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;HE染色检测大鼠RGC数量,免疫组织化学染色及Western blot检测大鼠视网膜ECH相关蛋白1(ECH-associated protein 1,Keap1)、核因子NF-E2相关因子(nuclear factor erythroid-2-related factor-2,Nrf2)、血红素氧合酶-1(heme oxygenase-1,HO-1)蛋白表达.结果 与CON组相比,DM组血糖、MDA含量、Keap1及Nrf2表达明显增加,SOD活性及HO-1表达明显下降.而经过12周治疗后上述表现均有明显改善.结论 TFF通过降低血糖,增强大鼠视网膜的抗氧化能力,保护糖尿病状态下的RGC损伤,与调控Keap1-Nrf2/HO-1信号通路有关.     

壳聚糖球形多孔微载体支持下人肝细胞L-02的高浓度细胞培养

背景：微载体培养技术作为一项体外高浓度细胞培养技术,近年来已在肝细胞的体外培养中得到应用。 目的：对壳聚糖球形多孔微载体培养的人肝细胞L-02进行定时的形态学观察。 方法：以自制的壳聚糖球形多孔微载体样本为支架来培养人肝细胞L-02设为实验组;无壳聚糖球形多孔微载体支持下人肝细胞的培养设为对照组。对两组细胞进行定时的细胞计数,并对实验组进行形态学观察,包括倒置相差生物显微镜观察和扫描电子显微镜观察。 结果：两组培养的细胞数量均呈现前3 d增长,在第3天细胞数量达到最高值;而且实验组3个样本培养的细胞数明显高于对照组无微载体培养的细胞数量(P < 0.05),实验组各样本之间差异无显著性意义(P > 0.05);倒置相差生物显微镜下动态观察,可见前3 d微载体表面黏附生长的肝细胞则逐渐增多,第3天可见大部分微载体表面有许多肝细胞黏附成团,总的存活率均在90%以上,且肝细胞保持着良好的形态学结构;扫描电子显微镜观察,微载体表面、切面和内部均可看到有许多球状肝细胞紧密黏附。提示,以自制的壳聚糖球形多孔微载体作为一种支架,在体外三维环境下可以进行高浓度细胞培养。     

巨噬细胞PDHA1基因敲除对非酒精性脂肪性肝病小鼠肝细胞凋亡的影响

目的：探讨巨噬细胞丙酮酸脱氢酶E1 α1亚基(pyruvate dehydrogenase E1 subunit alpha 1, PDHA1在同型半胱氨酸(homocysteine, Hcy)诱导的小鼠非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)中对肝细胞凋亡的作用。方法：随机选取6周龄体重相近的PDHA1基因正常野生型小鼠和巨噬细胞特异性PDHA1基因敲除(PDHA1^{iΔMΦ/iΔMΦ})小鼠各12只,均分别给予普通饮食和高Hcy饮食喂养12周后用于后续实验。应用琼脂糖凝胶电泳技术对PDHA1^{iΔMΦ/iΔMΦ}小鼠进行基因鉴定;Western blot检测两种基因型小鼠骨髓巨噬细胞PDHA1蛋白表达;使用全自动生化分析仪检测小鼠血清Hcy和丙氨酸转氨酶(alanine aminotransferase, ALT)水平;试剂盒检测肝组织上清液甘油三酯(triglyceride, TG)和ALT水平;苏木精-伊红(hematoxylin-eosin, HE)染色观察小鼠肝组织结构改变;q...     

三七总皂甙对脂肪变性L02肝细胞TG含量及LXRα mRNA表达的影响

目的： 观察三七总皂甙(PNS)对脂肪变性L02肝细胞内甘油三酯(TG)含量及肝X受体α（LXRα）mRNA表达的影响,探讨其对脂肪变性肝细胞的降脂作用及机制。方法: 采用50%小牛血清诱导L02肝细胞48 h建立肝细胞脂肪变性模型,采用MTT法测定PNS作用于脂肪变性肝细胞的适宜浓度,随后将其分为5组,模型组、自然恢复组、PNS低剂量组（10 mg·L-1）、PNS高剂量组（50 mg·L-1）,并设正常组,除模型组继续予含50%小牛血清的 RPMI-1640培养基培养外,余组均改予含10%小牛血清培养。药物作用24 h后,油红O染色观察肝细胞内脂滴变化,全自动生化仪检测肝细胞内TG含量,运用RT-PCR法检测肝细胞内LXRα mRNA的表达。结果: 与正常组比较,油红O染色示模型组肝细胞内橘红色脂滴明显增加,并出现脂滴融合现象,模型组TG含量明显升高（P＜0.01）。PNS治疗24 h后,PNS各治疗组与自然恢复组比较,肝细胞内TG含量均明显减少（P＜0.05）,以低剂量组下降更为显著（P＜0.01）;油红O染色显示,PNS低剂量组肝细胞内脂滴数减少最为明显。与正常组比较,模型组肝细胞LXRα mRNA的表达明显上调（P＜0.01）;与自然恢复组比较,PNS各治疗组肝细胞LXRα mRNA的表达量均有下降,以低剂量组下降显著（P＜0.05）。结论: PNS能显著降低脂肪变性肝细胞内TG含量,减轻肝细胞脂肪变性。LXRα mRNA的高表达与肝细胞脂肪蓄积密切相关,PNS可能是通过下调LXRα mRNA的表达来改善肝细胞的脂肪变性。     

Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice

BackgroundComplement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known.MethodsC57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32% kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a.ResultsChronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα.ConclusionTaken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding.     

褪黑素对烟雾吸入所致大鼠急性肺损伤的保护作用

目的通过建立褪黑素干预大鼠烟雾吸入性损伤模型,探讨褪黑素对急性肺损伤的保护作用。方法成年清洁级雄性SD大鼠72只随机分为空白组、损伤组和褪黑素组。空白组不做任何处理,损伤组于吸入性损伤处理后腹腔注射1%乙醇生理盐水（10ml/kg）,褪黑素组于吸入性损伤处理后腹腔注射褪黑素（10mg/kg,1次/8h）。三组大鼠分别在3h、12h、24h三个时相腹主动脉取血2ml后处死,动脉血离心后检测肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）含量和白细胞介素10（IL-10）。肺组织匀浆测超氧化物歧化酶（SOD）、丙二醛（MDA）、髓过氧化物酶（MPO）的含量。取右下肺组织作病理切片,光镜下观察肺组织病理情况。结果光镜下见空白组大鼠肺泡腔结构完整,壁光滑;损伤组肺泡壁增厚,肺间质炎症细胞浸润;褪黑素组肺组织较损伤组病理表现有所减轻。褪黑素组各时相点血清TNF-α和IL-6含量高于空白组（P〈0.05）,低于损伤组（P〈0.05）。损伤组各时相点IL-10含量与空白组相比无统计学差异（P〉0.05）,而褪黑素组IL-10含量与空白组、损伤组相比均升高（P〈0.05）。褪黑素组各时相点肺组织SOD含量均高于损伤组（P〈0.05）,低于空白组（P〈0.05）。褪黑素组各时相肺组织MDA和MPO含量均高于空白组（P〈0.05）,低于损伤组（P〈0.05）。结论褪黑素可以减轻炎症及氧化应激,对烟雾吸入性损伤所致急性肺损伤发挥一定的保护作用。     

CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation

The role of oxidative stress in alcoholic liver disease and cytokeratin aggresome formation is the focus of this in vitro study. HepG2 cells transduced to over express CYP2E1 (E47) and control HepG2 cells (C34) were first treated with arachidonic acid, then Fe-NAT, and finally with ethanol. In the E47 ethanol-treated cells, CYP2E1 was induced and a higher level of reactive oxygen species and carbonyl proteins were generated. The proteasome activity decreased significantly in the E47 ethanol-treated cells. This inhibition was prevented when CYP2E1 was inhibited by DAS. Microarray analysis showed gene expression down regulation of the proteasome subunit, as well as ubiquitin pathway proteins in the E47 ethanol-treated cells. 4-Hydroxynonenal (4-HNE) adducts were increased in the E47 cells treated with ethanol. Furthermore, the immunoprecipitated 4-HNE modified proteins from these cells stained positive with antibodies to the proteasome subunit alpha 6. These results indicate that the ethanol induced CYP2E1 generates oxidative stress that is responsible for the decrease in proteasome activity. Cytokeratin 8 and 18 were induced by ethanol treatment of E47 cells and polyubiquitinated forms of these proteins were found in the polyubiquitin smear upon Western blots analysis. Cytokeratin aggresomes and Mallory body-like inclusions formed in the ethanol-treated E47 cells, indicating that the ubiquitinated cytokeratins accumulated as a result of the inhibition of the proteasome by ethanol treatment when oxidation of ethanol induced oxidative stress. This is the first report where ethanol caused Mallory body-like cytokeratin inclusions in transformed human liver cells in vitro.     

牛磺酸对百草枯中毒大鼠肾损伤的作用及机制研究

目的:探讨不同剂量牛磺酸对百草枯中毒大鼠肾脏氧化应激和炎症反应的影响。方法:选取48只雄性SD大鼠随机分为阴性对照组、百草枯染毒组、百草枯染毒+小剂量牛磺酸组和百草枯染毒+大剂量牛磺酸组。采用生化检测仪检测大鼠血清肌酐及尿素氮水平;比色法检测血标本中丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)水平评估氧化应激状态;另以ELISA法检测血标本中IL-6及细胞间黏附分子1(ICAM-1)水平评估炎症反应;DHE荧光探针检测肾脏活性氧簇(reactive oxygen species,ROS)水平;Western blot法检测大鼠肾脏标本丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)中p-P38 MAPK、p-JNK和pERK1/2的蛋白水平;并以real-time PCR法检测大鼠肾脏内TNF-α、TGF-β1及IL-6的mRNA水平。结果:百草枯中毒大鼠血清肌酐及尿素氮增高,牛磺酸干预后降低了中毒大鼠的肌酐及尿素氮水平,且大剂量牛磺酸组的肌酐及尿素氮水平更低。牛磺酸的干预不仅明显减轻了肾脏组织的氧化应激与炎症反应,同时也降低了百草枯中毒大鼠肾脏的MAPK活性。结论:牛磺酸干预能减轻百草枯中毒大鼠的肾损伤,其作用机制可能与下调了肾脏MAPK活性、减轻了肾脏氧化应激及炎症反应有关。     

内皮素-1对COPD炎症和氧化应激反应的影响

目的:研究内皮素-1对慢性阻塞性肺疾病(COPD)炎症和氧化应激反应的影响。方法:收集健康不吸烟者(30例)、健康吸烟者(30例)和COPD患者(29例)并诱导其产生痰液,检测内皮素-1在诱导痰中的浓度。采用香烟烟雾提取物刺激SD大鼠,构建肺气肿模型,采用内皮素A受体拮抗剂BQ123和非选择性内皮素受体拮抗剂波生坦进行干预,实验分为对照组、香烟烟雾干预组、选择性内皮素受体拮抗组和非选择性内皮素受体拮抗组。采用Western blot法测定肺组织中cleaved caspase-3的蛋白水平;明胶酶谱法检测肺组织中基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)的活性;ELISA法检测肺组织上清液中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的浓度;采用生物抗氧化能力(BAP)检测试剂盒检测血清中BAP。结果:内皮素-1在健康吸烟者和COPD患者诱导痰中的浓度显著高于健康不吸烟者(P0.05);COPD患者诱导痰中内皮素-1的浓度高于健康吸烟者(P0.05)。香烟烟雾干预组肺组织中cleaved caspase-3蛋白水平、MMP-2和MMP-9的活性及上清液中TNF-α和IL-1β的含量显著高于对照组(P0.05);内皮素A受体拮抗剂能显著抑制肺组织中cleaved caspase-3蛋白水平、MMP-2和MMP-9的活性及上清液中TNF-α和IL-1β的含量(P0.05)。香烟烟雾干预组血清中的BAP较对照组显著降低(P0.05);内皮素A受体拮抗剂能显著增加血清中的BAP(P0.05)。结论:内皮素-1可能通过调节细胞凋亡、基质金属蛋白酶活性、炎症以及氧化应激反应在COPD发生发展中发挥重要作用。     

肌肽对高糖诱导的大鼠H9C2心肌细胞损伤的保护作用及其机制

目的 研究肌肽对高糖诱导受损的大鼠心肌细胞（H9C2）的保护作用及其机制。 方法 用含50 mmol/L葡萄糖的高糖培养液建立高糖损伤模型,实验观察组给予5、15 mmol/L肌肽进行保护。MTT检测各组H9C2心肌细胞活力;ELISA测定培养液中IL-1β、IL-6和TNF-α炎症因子浓度含量;试剂盒检测细胞中SOD、MDA、AST和LDH活性;二氢乙锭测定细胞中活性氧含量;免疫印迹测定细胞中bax、bcl-2、p65和IκB-α的蛋白表达。 结果 肌肽预处理组细胞内活性氧含量下降,SOD活性升高,AST和LDH活性减弱,MDA含量降低;其培养液中炎症因子含量明显降低,细胞核中p65蛋白水平降低,胞浆中IκB-α蛋白水平升高,bax和bax/bcl-2比值降低。 结论 肌肽能够减轻高糖诱导的H9C2心肌细胞损伤,降低细胞炎症反应,其机制可能与ROS/NF-κB信号通路有关。     

Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with the effects of antioxidation, anti-inflammation and anti-fibrosis that has been shown to induce damage in liver. The purpose of this study is to investigate the effects and possible mechanisms of PTX on thioacetamide (TAA)-induced acute liver injury in rats. Male Sprague-Dawley (SD) rats were divided into four groups: control, PTX, TAA and PTX+TAA treated groups. Rats were administrated TAA together with or without PTX for a week and sacrificed 24 h after the last intragastric administration of PTX. Histopathological analysis was carried out. The liver function, the indices of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) in liver tissues, and pro-inflammatory cytokines expressions were examined. The mRNA level of NF-κB p65 in liver was also determined. PTX significantly attenuated TAA-induced liver injury. The serum transaminase and MDA levels were reduced while the levels of SOD and GSH were increased, as compared with the TAA-treated group. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and the nuclear factor-κB (NF-κB) activation induced by TAA. In addition, the histopathological analysis showed that the range and degree of liver tissue lesions were improved obviously in PTX treated group. Pentoxifylline could ameliorate the effects of thioacetamide-induced acute liver injury in rats by inhibiting oxidative stress, expressions of pro-inflammatory cytokines and NF-κB activation.     

Hepatoprotective effect of 3-alkynyl selenophene on acute liver injury induced by D-galactosamine and lipopolysaccharide

The aim of this study was to investigate the hepatoprotective effect of 3-alkynyl selenophene (compound a), a selenophene compound, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in rats. The animals received compound a (25 and 50 mg/kg; per oral, p.o.) in the first day of treatment. In the second day, the rats received D-GalN (500 mg/kg; intraperitoneal, i.p.) and LPS (50 μg/kg; intraperitoneal, i.p.). Twenty-four hours after D-GalN/LPS administration animals were euthanized to the biochemical and histological analysis. Compound a (25 and 50 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by D-GalN/LPS. Compound a at 50 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by D-GalN/LPS. The inhibition of δ-aminolevulinic dehydratase (δ-ALA-D) activity and the decrease of ascorbic acid levels caused by D-GalN/LPS were protected by compound a (25 and 50 mg/kg). Glutathione S-transferase (GST) and catalase activities were not altered in all groups. The histological data showed that sections of liver from D-GalN/LPS-treated rats presented massive hemorrhage, the presence of inflammatory cells and necrosis. Compound a attenuated D-GalN/LPS-induced hepatic histopathological alterations. Based on the results, we demonstrated the hepatoprotective effect of compound a on acute liver injury induced by D-GalN/LPS.     

金丝桃苷对CCl4诱导大鼠急性肝损伤抗氧化应激研究

目的研究金丝桃苷（Hyp）对四氯化碳（CCI。）诱导大鼠急性肝损伤的治疗作用。方法采用大鼠CCl4急性肝损伤模型,观察Hyp对急性肝损伤大鼠肝脏组织病理学改变的影响;检测肝组织匀浆中超氧化物歧化酶（T-SOD）、谷胱甘肽（GSH）的活性及丙二醛（MDA）含量变化。结果CCl4模型组大鼠肝组织HE染色病理检测结果见明显炎症变性死及纤维组织增生现象;Hyp高剂量60mg／kg、中剂量30mg／kg治疗组的肝组织病理改变明显改善;Hyp治疗组肝组织中T—SOD、GSH活性明显升高,MDA含量明显降低,并存在量效关系。结论Hyp对CCl4引起的大鼠急性肝损伤有较好的治疗作用,其机制可能与其抗氧化活性有关。