注射用丹酚酸A防治肝纤维化的实验研究

目的：探讨注射用丹酚酸A抗肝纤维化的作用,为丹酚酸A的临床应用提供理论依据。方法采用CCl4体外诱导肝细胞损伤,观察丹酚酸A对肝细胞活性及其细胞培养上清液ALT、AST、LDH水平和细胞裂解液中SOD活性和MDA含量的变化;另采用皮下注射CCl4诱导大鼠肝纤维化模型,观察丹酚酸A对肝纤维化大鼠血清LN、HA、SOD和MDA含量的影响以及肝脏组织病理改变情况。结果与模型对照组比,丹酚酸A高、低剂量组和Vit E组的细胞存活率显著提高（P ＜0.01）,丹酚酸A高剂量组ALT、AST和LDH活性显著降低（P ＜0.01）,丹酚酸A高剂量组和Vit E组SOD活性明显升高（P ＜0.05）,MDA含量显著降低（P ＜0.05）;体内试验发现,与模型对照组比,丹酚酸A高剂量组纤维化大鼠的血清LN和HA水平显著降低（P ＜0.05）,高、低剂量组SOD活性显著升高（P ＜0.05, P ＜0.01）,MDA含量显著降低（P ＜0.01, P ＜0.05）,并能改善肝脏病理形态。结论注射用丹酚酸A可通过抗脂质过氧化作用,起到保护肝细胞,减轻肝纤维化的作用。     

新安软胶囊对大鼠脂肪肝动物模型的影响

目的:研究新安软胶囊对大鼠脂肪肝模型动物的影响.方法:建立大鼠脂肪肝动物模型后,以血清中生化指标(ALT、AST、LDL、HDL-C)测定、血清和组织中CHO、TG、MDA、SOD含量测定等为检测指标,比较新安软胶囊的量效与时效关系.结果:①每个新安软胶囊组与模型组及对照组比较均能明显降低ALT、AST、LDL、CHO、TG、MDA、SOD (P＜0.05),以及明显升高HDL-C(P＜0.05),其剂量效果是新安软胶囊62.5 mg/kg组＜125mg/kg组＜250 mg/kg组,其时间效果是用药后第2周＜第4周＜第6周;②新安软胶囊中、大剂量组与模型组比较有明显统计学差异(P＜0.05).结论:新安软胶囊对大鼠脂肪肝模型具有明显的治疗作用.     

小茴香对肝纤维化大鼠脂质过氧化水平的影响

目的:研究小茴香对肝纤维化大鼠的脂质过氧化水平的影响。方法:取Wister大鼠100只,随机取12只设为正常组,其余采用四氯化碳(CCL4)复合因素法复制肝纤维化大鼠模型,复制成功后随机分为模型对照组、小茴香组和复方丹参组(n=12);相应药物干预8周后,镜检肝组织形态学改变;全自动生化分析仪检测外周血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平与血清总蛋白(TP)、白蛋白(ALB)含量;生化法检测肝组织羟脯氨酸(HYP)与血清丙二醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)活性。结果:HE结果显示:模型组肝脏炎症与脂肪变性明显,经小茴香干预后明显改善。生化检测结果显示:与正常组比较,模型组ALT、AST水平显著升高(P<0.05),TP、ALB含量显著降低(P<0.05),HYP、MDA含量显著增加(P<0.05),而SOD、GSH-PX和CAT活性显著降低(P<0.05);与模型组比较,小茴香组ALT、AST水平显著下降(P<0.05),TP、ALB水平显著升高(P<0.05);HYP、MDA含量显著降低(P<0.05),SOD、GSH-PX和CAT活性显著提高(P<0.05)。结论:小茴香的抗肝纤维化作用可能与调节大鼠脂质过氧化水平有关。     

黄芪多糖预防2 型糖尿病大鼠肝损伤的实验研究

目的:研究分析黄芪多糖(Astragalus polysaecharides,APS)在预防2型糖尿病大鼠肝损伤的作用。方法:Wistar大鼠72只,其中48只以小剂量链脲佐菌素(Streptozotocin,STZ)建立2型糖尿病大鼠模型,并随机分为模型对照组(B组)和APS组(C组),余24只大鼠为正常对照组(A组)。C组大鼠给予APS 400 mg/kg/d灌胃,A、B组分别给予等量生理盐水。分别于第0、2、4、6周检测3组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)以及丙二醛(MDA)水平,透射电镜下观察3组大鼠肝细胞超微结构变化。结果:第0、2周时B、C组大鼠ALT、AST、SOD以及MDA水平比较无显著差异(P0.05)。第4、6周时,C组大鼠ALT、AST以及MDA水平均高于A组,但低于B组;而SOD水平低于A组,但高于B组;差异均有统计学意义(P0.05)。电镜下观察,A组肝细胞内大量线粒体、内质网,结构完好,未见损伤;B组细胞器数量减少,线粒体及内质网形态异常,膜结构破损,细胞空化;C组细胞器也存在损伤,但较B组明显减轻。结论:APS可增加肝细胞抗氧化酶的活性,促进氧自由基的清除,减少肝细胞损伤,对预防2型糖尿病引起的肝功能损害有一定的价值。     

解酒护肝饮解酒及对急慢酒精性肝损伤的保护作用

为了评价解酒护肝饮解酒效果及其对急、慢性酒精性肝损伤保护作用机制,本研究通过建立醉酒模型,确定致醉剂量;通过醉酒睡眠实验比较解酒护肝饮解酒特性;通过测定醉酒小鼠血乙醇含量的变化,研究解酒护肝饮对乙醇代谢的影响;通过建立急慢性酒精性肝损伤模型,测定AST、ALT、SOD活性,GSH、MDA水平,HE染色切片观察肝组织形态学的变化。研究发现小鼠最佳致醉剂量为11 m L/kg;与模型组比较,解酒护肝饮高(HD)、中剂量组(MD)均可延长醉酒时间、缩短醒酒时间(p<0.05),高、中剂量组可降低酒精灌胃后2 h、3 h时间点血乙醇含量(p<0.05);与模型组比较,急慢性酒精肝损伤模型各剂量组均能显著降低血清AST、ALT活性(p<0.05),急性酒精性肝损伤模型中,各剂量组肝组织SOD、GSH水平上升(p<0.05),MDA水平下降(p<0.05),而在慢性酒精性肝损伤模型肝组织中,低剂量组(LD)的SOD、GSH及MDA水平没有统计学差异;病理切片观察可见,急慢性酒精肝损伤模型高、中、低剂量组均能显著改善肝组织因乙醇而导致的肝损伤,并且高、中剂量组效果较好。本研究表明解酒护肝饮可显著延长醉酒时间,缩短醒酒时间,降低血乙醇的含量,对酒精诱导的肝损伤有较好的保护作用。     

牛磺酸对四氯化碳诱导的小鼠肝纤维化模型中IL-6影响

目的:观察牛磺酸对四氯化碳(CCl4)诱导的小鼠肝纤维化模型血清中IL-6的影响。方法:将30只雄性SPF级C57B/L小鼠随机分为空白对照组,模型组和牛磺酸组,每组各10只。空白对照组给予100%花生油1 m L/Kg腹腔注射,每周2次,共10周;模型组给予含20%CCl4的花生油1 m L/Kg腹腔注射,每周2次,共10周;牛磺酸组给予含20%CCl4的花生油1 m L/Kg腹腔注射,每周2次,共10周,并从第3周起给予牛磺酸500 mg/Kg/d灌胃至第10周。在第10周通过摘除眼球取血,检测小鼠血清中的透明质酸(HA)、层黏连蛋白(LN)、三型前胶原(PCⅢ)、四型胶原(Ⅳ-C)、丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、IL-6的含量;检测肝脏组织中超氧化物歧化酶(SOD)和丙二醛(MDA)的含量;计算肝脏指数;观察小鼠肝脏的HE染色病理组织学改变。结果:模型组与空白对照组相比小鼠血清中HA、LN、PCⅢ、Ⅳ-C、ALT、AST和IL-6水平显著升高(P0.05),肝脏组织中SOD和MDA水平显著升高(P0.05),肝脏指数增加(P0.05),病理检查显示肝细胞坏死并出现脂肪空泡、纤维组织增生和炎细胞浸润;牛磺酸组与模型组相比小鼠血清中HA、LN、PCⅢ、Ⅳ-C、ALT、AST和IL-6的水平显著降低(P0.05),肝脏组织中SOD显著升高(P0.05),MDA水平显著降低(P0.05),肝脏指数降低(P0.05),病理检查显示肝脏组织中无炎性浸润、脂肪空泡和无纤维组织沉积。结论:牛磺酸可以降低肝纤维化小鼠血清中IL-6的含量,减轻CCl4诱导小鼠肝纤维化程度。     

低强度激光治疗对游泳大鼠氧化应激和功能恢复的影响

本研究的目的是确定低强度激光疗法(LLLT)联合有氧运动对机体氧化应激和心肺功能恢复的影响。本研究测试了60只SD大鼠,将大鼠随机分为对照组、低强度激光治疗组、运动组和低强度激光治疗+运动组(n=15)。检测了各组大鼠有氧运动训练或低强度激光治疗6周后的最大摄氧量(VO_2max 0.75)和最大运动速度;检测了各组大鼠腓肠肌中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)和丙二醛(MDA)水平以及大鼠血清肌酸激酶(CK)、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平。研究显示,低强度激光治疗+运动组大鼠的最大摄氧量和最大运动速度均显著高于其他组(p0.05)。低强度激光治疗+运动组的CAT、SOD和GPx活性均显著高于其他组(p0.05),而MDA水平显著低于其他组(p0.05)。低强度激光治疗+运动组的血清CK、AST和ALT水平均显著低于其他组(p0.05)。本研究表明在有氧运动基础上进行低强度激光治疗可有效提高机体的心肺功能,改善抗氧化防御系统,减少脂质过氧化损伤和运动损伤。     

咖啡酸对慢性铝负荷大鼠肝损伤的保护作用

目的观察5-脂氧酶(5-LO)抑制剂咖啡酸对慢性铝负荷所致大鼠肝损伤的保护作用,并初步探讨其可能的机制。方法将SD大鼠分为空白对照组、慢性铝负荷模型组、咖啡酸低剂量组和咖啡酸高剂量组,除空白对照组外,每组大鼠每天灌胃给予葡萄糖酸铝(Al3+200 mg·kg-1·d-1),给药组大鼠在给铝后1周分别灌胃给予2个剂量的咖啡酸,每周5 d,连续20周。建模完成后,用生化法检测大鼠血清中丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)活性,以及肝组织丙二醛(MDA)含量,超氧化物歧化酶(SOD)活性,采用苏木精-伊红染色法观察大鼠肝脏组织形态学变化,用免疫组织化学法检测大鼠肝组织5-LO蛋白表达情况。结果与空白对照组大鼠比较,慢性铝负荷模型组大鼠血清ALT、AST、ALP活性显著升高,肝组织MDA含量显著增加,SOD活性显著下降,肝细胞出现明显空泡性变、点状坏死、肝细胞排列紊乱,肝组织5-LO在血管周围肝细胞胞浆中表达明显。与铝负荷模型组比较,给予咖啡酸后大鼠肝细胞损伤减轻,血清ALT、AST、ALP活性明显降低,肝组织MDA含量显著减少,SOD活性显著上升,肝组织5-LO表达明显减少。结论咖啡酸能减轻慢性铝负荷所致肝损伤,机制可能与其抑制5-LO表达、减轻氧化应激反应损伤有关。     

罗格列酮对血脂异常大鼠氧化应激及炎症反应的影响

目的:探讨罗格列酮对血脂异常大鼠的氧化应激和炎症反应损伤的保护作用。方法:2月龄健康成年雄性大鼠30只,随机分成3组,每组10只,分别为对照组(普通饲料饲养)、高脂组(高脂饲料饲养)和罗格列酮组(高脂饲料饲养后5 mg·kg-1罗格列酮灌胃),其中血脂异常模型构建时间为5周,罗格列酮的干预时间为1周。第6周实验结束后对各组大鼠进行准确称重,采血,离心留取上清,全自动生化分析仪用于检测待测血清中甘油三脂(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平,酶联免疫吸附法(ELISA)用于检测过氧化物歧化酶(SOD)、丙二醛(MDA)、C-反应蛋白(CRP)、不对称二甲基精氨酸(ADMA)及一氧化氮(NO)产生量。在无菌条件下分别分离各组大鼠肾周、附睾和腹膜后的脂肪组织并准确称量,即为大鼠的内脏脂肪重量,并对上述10项指标进行两两相关性分析。结果:与对照组相比,高脂组的大鼠体重和内脏脂肪重量均显著增加(P0.05),血清TG、TC和LDL-C水平均显著增加(P0.05);NO产生量和血清SOD水平均显著减少(P0.05);血清MDA、CRP和ADMA水平均显著增加(P0.05)。与高脂组相比,罗格列酮组的大鼠体重和内脏脂肪重量均显著降低(P0.05),TG、TC和LDL-C水平略有改善,但差异并不显著(P0.05);NO产生量和血清SOD水平均显著增加(P0.05);血清MDA、CRP、ADMA水平均显著减少(P0.05),血清TG水平和SOD水平呈负相关(Y=-0.014X+2.967,P=0.001)。结论:罗格列酮对血脂异常的大鼠具有氧化应激和炎症反应损伤的保护作用。     

复方五味子提取物对力竭游泳大鼠的抗疲劳作用

五味子、黄芪、丹参、枸杞和马齿苋均具有较好的抗氧化活性和抗疲劳功效。然而,尚不清楚该5种中药材组合的应用效果。本研究将这5种植物药材进行混合提取,得到了复方五味子提取物。然后考察了不同剂量的复方五味子提取物对力竭游泳大鼠的运动能力和生化指标的影响。研究显示,复方五味子提取物以剂量依赖性方式提高大鼠的力竭游泳时间(p<0.05)。复方五味子提取物以剂量依赖性方式降低血清Lac和BUN水平并升高NEFA水平(p<0.05)。复方五味子提取物显著升高大鼠体内SOD和CAT水平,并显著降低MDA水平(p<0.05)。复方五味子提取物显著降低大鼠血清CK、AST和ALT水平(p<0.05),并减弱骨骼肌组织病变程度。本研究表明,复方五味子提取物具有较好的抗疲劳作用,可通过减少乳酸堆积、增加脂肪动员、减弱氧化应激损伤来提高机体运动能力。     

川芎嗪促进大鼠部分肝切除后修复性再生机制的研究

目的:探讨大鼠部分肝切除后肝功能的变化及川芎嗪对肝修复性再生能力的影响。方法:在相同月龄的动物中按体重均衡的原则随机分组。实验动物共分为5组:设正常对照组(对照组)、青年假手术对照组(假术组)、青年肝切除组(青切组)、中年肝切除组(中切组)和中年肝切除治疗组(切治组),每组动物10只,常规饲养,自由饮水。参照Higgins and Aderson给大鼠施行肝脏70%切除手术,中切组大鼠术前以川芎嗪(200 mg/kg/d)腹腔注射7d,其余组注射生理盐水。假术组大鼠以同样的手术程序打开腹腔但不施行肝部分切除术。各组施行手术动物在切除术后24 h沿腹中线切开动物腹腔,于腹主动脉两髂分支处取血分离血清,切取所有肝脏,待测。采用试剂盒法分别测定各组血清中丙氨转氨酶(ALT)、谷草转氨酶(AST)含量;肝脏匀浆后,采用八木国夫法检测肝组织中丙二醛(MDA)含量,采用western blot法测定肝组织中核增殖抗原(PCNA)和铜锌超氧化物歧化酶(SOD1)、锰超氧化物歧化酶(SOD2)的蛋白表达。结果:与中切组相比手术动物相比,切治组组大鼠血清中ALT、AST水平显著降低(P<0.05),肝细胞中PCNA表达显著升高(P<0.05),肝组织中MDA含量显著降低(P<0.05);肝组织中SOD1、SOD2表达显著增加。结论:肝脏切除70%后,肝功受损,氧化应激增加,但核增殖能力增强。川芎嗪可以抑制肝切手术导致的氧化应激损伤,促进SOD的表达,抑制MDA的升高,降低ALT、AST水平,提高PCNA的表达。提示中年大鼠肝切除后肝功能受损与氧化应激相关,给予抗氧化药物能够促进肝再生修复能力,青年肝切除手术大鼠肝的修复能力强于中年动物。     

不同剂量乳化异氟醚预处理对大鼠肝脏缺血再灌注损伤的保护作用

摘要 目的：探究不同剂量乳化异氟醚预处理对大鼠肝脏缺血再灌注损伤的保护作用。方法：将48只成年雄性大鼠随机分为六组：假手术组、缺血对照组、脂肪乳组、低剂量乳化异氟醚组、中剂量乳化异氟醚组和高剂量乳化异氟醚组,每组8只。检测血清中酶的含量,观察肝细胞损伤程度,直观的反应乳化异氟醚预处理对肝脏缺血再灌注损伤的影响。结果：不同组别大鼠肝脏再灌注后ALT、AST、LDH和MDA含量,SOD活性和肝细胞坏死比例均具有显著差异,随着再灌注时间的延长,各组大鼠血清ALT、AST和LDH含量均明显增加（均P＜0.05）。再灌注后1 h、2 h和4 h中剂量乳化异氟醚组大鼠血清ALT、AST和LDH含量均显著低于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组（均P＜0.05）。中剂量乳化异氟醚组大鼠肝组织匀浆中MDA含量和肝细胞坏死比例均显著低于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组,SOD活性显著高于缺血对照组、低剂量乳化异氟醚组和高剂量乳化异氟醚组（均P＜0.05）。结论：中等剂量乳化异氟醚预处理组中血清中酶含量最低,肝组织匀浆中MDA含量最低,SOD活性水平最高,肝细胞损伤程度最轻,对大鼠肝脏缺血再灌注的保护作用最好。     

Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP-induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.     

Protective effects of C-phycocyanin on alcohol-induced subacute liver injury in mice

Excessive and long-term alcohol consumption leads to liver disease and low immunity. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Arthrospira (Spirulina) platensis, exerts protective effects against chemical-induced organ damage and improves immunity. In this study, we investigated whether C-PC could protect against ethanol-induced subacute liver injury and improve immunity. KM mice with ethanol-induced liver injury were established, and animals were divided into three groups that were treated with high, medium, and low doses of C-PC. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), total bilirubin (TBIL), liver homogenate malondialdehyde (MDA), and superoxide dismutase (SOD) levels were measured. In addition, the number of thymus T cell subsets was assessed, and liver sections were examined pathologically. C-PC exhibited obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL, and MDA levels and increased SOD content significantly in the liver. C-PC also increased serum CD3+ and CD4+ cell activation and T cell proliferation significantly compared with the model group. The structure of the hepatic lobules was clear, the liver sinus returned to normal, and the liver cell cords were arranged in neat rows. Therefore, C-PC could protect against ethanol-induced subacute liver injury significantly.     

紫檀芪调节Keap-1/Nrf2/HO-1信号通路对非酒精性脂肪肝大鼠氧化应激和细胞凋亡的影响

摘要 目的：研究紫檀芪调节Kelch样ECH关联蛋白1（Keap-1）/核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路对非酒精性脂肪肝（NAFLD）大鼠氧化应激和细胞凋亡的影响。方法：将60只SD大鼠随机分为对照组、模型组、紫檀芪低剂量组（30 mg/kg）、紫檀芪高剂量组（60 mg/kg）、紫檀芪（60 mg/kg）+N-（4-（2,3-二氢-1-（2''-甲基苯甲酰）-1H-吲哚-5-基）-5-甲基-2-噻唑基）-1,3-苯并二氧唑-5-乙酰胺（ML385）（30 mg/kg）组，每组12只。模型组与药物干预组大鼠以高脂饲料饲养诱导NAFLD模型，对照组大鼠以普通饲料饲养，各组连续喂养12周。以紫檀芪和ML385分组处理14 d后（对照组以等剂量生理盐水处理），检测各组大鼠脂代谢指标[三酰甘油（TG）、总胆固醇（TC）及游离脂肪酸（FFA）水平]、肝指数、肝功能指标[谷丙转氨酶（ALT）及谷草转氨酶（AST）]水平、血清白细胞介素（IL）-17、IL-6、IL-10、氧化应激指标[丙二醛（MDA）、超氧化物歧化酶（SOD）及过氧化氢酶（CAT）]水平；原位末端标记法（TUNEL）染色检测各组大鼠肝细胞凋亡率；蛋白免疫印迹法检测各组大鼠肝组织凋亡相关蛋白及Keap-1/Nrf2/HO-1通路相关蛋白表达。结果：与对照组相比，模型组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平显著降低（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1及Bax表达水平显著升高（P＜0.05）。与模型组相比，紫檀芪低、高剂量组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平均升高（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1、Bax表达水平均降低（P＜0.05）；与紫檀芪低剂量组相比，紫檀芪高剂量组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平升高（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Keap-1及Bax表达水平降低（P＜0.05）；与紫檀芪高剂量组相比，紫檀芪+ML385组大鼠血清IL-10、SOD及CAT水平、肝组织Nrf2、HO-1、Bcl-2表达水平降低（P＜0.05），TG、TC及FFA水平、肝指数、ALT及AST水平、血清IL-17、IL-6、MDA水平、肝细胞凋亡率、肝组织Bax表达水平升高（P＜0.05）。结论：紫檀芪可能通过激活Keap-1/Nrf2/HO-1信号通路，改善NAFLD大鼠脂代谢水平，调节炎症反应及氧化应激，减轻肝组织脂肪变性及细胞凋亡。     

Copper Intoxication; Antioxidant Defenses and Oxidative Damage in Rat Brain

Copper (Cu) is an integral part of many important enzymes involved in a number of vital biological processes. Even though Cu is essential to life, it can become toxic to cells, at elevated tissue concentrations. Oxidative damage due to Cu has been reported in recent studies in various tissues. In this study, we aimed to determine the effect of excess Cu on oxidative and anti-oxidative substances in brain tissue in a rat model. Sixteen male Wistar albino rats were divided into two groups: the control group, which was given normal tap water, and the experimental group, which received water containing Cu in a dose of 1 g/l. All rats were sacrificed at the end of 4 wk, under ether anesthesia. Cu concentration in the liver and in plasma alanine aminotransferase (ALT) and aspartate transaminase (AST) activities were determined. There were multiparameter changes with significant ALT and AST activity elevation and increased liver Cu concentration. In brain tissue, Cu concentration, superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and glutathione (GSH) concentrations were determined. Brain Cu concentration was significantly higher in rats receiving excess Cu, compared with control rats (p < 0.05). Our results showed that SOD activities and GSH levels in brain tissue of the Cu-intoxicated animals were significantly lower than in the control group (p < 0.01 and p < 0,001, respectively). The brain MDA levels were found to be significantly higher in the experimental group than in the control group (p < 0.001). The present results indicate that excessive Cu accumulation in the brain depressed SOD activities and GSH levels and resulted in high MDA levels in brain homogenate due to the lipid peroxidation induced by the Cu overload.     

小茴香对肝纤维化大鼠脂质过氧化水平的影响

目的：研究小茴香对肝纤维化大鼠的脂质过氧化水平的影响。方法：取Wister大鼠100只,随机取12只设为正常组,其余采用四氯化碳（CCL4）复合因素法复制肝纤维化大鼠模型,复制成功后随机分为模型对照组、小茴香组和复方丹参组（n=12）;相应药物干预8周后,镜检肝组织形态学改变;全自动生化分析仪检测外周血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平与血清总蛋白（TP）、白蛋白（ALB）含量;生化法检测肝组织羟脯氨酸（HYP）与血清丙二醛（MDA）含量及超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、过氧化氢酶（CAT）活性。结果：HE结果显示：模型组肝脏炎症与脂肪变性明显,经小茴香干预后明显改善。生化检测结果显示：与正常组比较,模型组ALT、AST水平显著升高（P〈0．05）,TP、ALB含量显著降低（P〈O．05）,HYP、MDA含量显著增加（P〈0．05）,而SOD、GSH—PX和CAT活性显著降低（P〈0．05）;与模型组比较,小茴香组ALT、AST水平显著下降（P〈0．05）,TP、ALB水平显著升高（P〈0．05）;HYP、MDA含量显著降低（P〈0．05）,SOD、GSH—PX和CAT活性显著提高（P〈0．05）。结论：小茴香的抗肝纤维化作用可能与调节大鼠脂质过氧化水平有关。     

Effects of Selenium and Vitamin E,in Addıtıon to Melatonin,Against Oxidative Stress Caused by Cadmium in Rats

The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutanous physiological saline. The first study group administered cadmium chloride (CdCl₂) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl₂ plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl₂ administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl₂ administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl₂ received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage.