核因子E2相关因子2基因启动子多态性对酒精性肝病小鼠感染创伤弧菌的影响

目的 探讨核因子E2相关因子2(nrf2)基因启动子336位点多态性对酒精性肝病小鼠感染创伤弧菌的影响.方法 取C57B6雄性小鼠,简单随机抽样法分为正常喂养组(A组,10只)、酒精性肝病组(B组,10只)、正常喂养且腹腔注射感染创伤弧菌组(C组,8只)、酒精性肝病感染创伤弧菌组(D组,110只),以基因测序法检测D组小鼠nrf2基因启动子336位点多态性,分为非突变组(336T)(D1组,7只)及突变组(336C)(D2组,10只).应用RT-PCR、Western-blotting、ELISA检测各组小鼠肝组织nrf2、肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)及高迁移率族蛋白B1(HMGB1)的基因及蛋白水平,观察小鼠肝组织病理变化.结果 A、B、C、D1、D2组小鼠在感染创伤弧菌48 h后肝组织nrf2基因的mRNA表达量中位数分别为0.115、0.173、0.211、0.764、0.352 (χ2=40.64,P<0.05);IL-10基因的mRNA表达量中位数分别为0.338、0.637、1.002、1.825、1.403(χ2=41.05,P<0.05);TNF-α基因的mRNA表达量中位数分别为0.140、0.254、0.372、0.399、0.699(χ2=38.16,P<0.05);HMGB1基因的mRNA表达量中位数分别为0.230、0.410、0.668、0.508、1.021(χ2=31.45,P<0.05).A、B、C、D1、D2组小鼠在感染创伤弧菌48 h后肝组织nrf2基因的蛋白表达量中位数分别为0.908、1.461、2.061、3.982、2.243(χ2=33.72,P<0.05);IL-10基因的蛋白表达量中位数分别为13.97、22.54、30.14、57.98、41.53(χ2=37.31,P<0.05);TNF-α基因的蛋白表达量中位数分别为114.07、142.94、175.44、174.60、266.11(χ2=32.29,P<0.05);HMGB1基因的蛋白表达量中位数分别为2.01、6.05、9.62、6.24、12.89(χ2=36.94,P<0.05).与A组比较,B组可见大量散在脂肪滴,呈空泡样改变,C组可见炎症细胞浸润,肝细胞条索紊乱,D组可见肝细胞充血水肿,肝小叶完整性破坏,汇管区可见扩张的肝管和静脉.结论 nrf2基因启动子336位点T→C突变使酒精性肝病C57B6小鼠体内nrf2表达明显降低,并加剧酒精性肝病C57B6小鼠在感染创伤弧菌时的炎症反应及脏器损害.

Abstract：

Objective To investigate the influence of genetic polymorphism in NF-E2-related factor-2(nrf2) gene promoter locus at 336 in alcoholic liver disease(ALD) with Vibrio vulnificus(VV) sepsis.Methods Through the simple random sampling method,C57B6 male mice were divided into normal feeding group(group A,10 mice),alcoholic liver disease group(group B,10 mice),normal feeding group infected with VV through intraperitoneal injection(group C,8 mice),alcoholic liver disease group infected with VV(group D,110 mice).Through gene sequencing method,nrf2 gene promoter 336 polymorphism in D group was analyzed and grouped into: non-mutation group(336T)( group D1,7 mice) and mutation group(336C)( group D2,10 mice ).Through RT-PCR,Western-blotting and ELISA method,expressions of nrf2,tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),high mobility group protein 1(HMGB1)gene and protein of liver were measured.The pathological changes in liver were recorded with light microscope.Results After infected with VV for 48 hours for A,B,C,D1,D2 group,the expression medians of nrf2 mRNA in liver were 0.115,0.173,0.211,0.764,0.352,respectively(χ2=40.64,P<0.05),the expression medians of IL-10 mRNA in liver were 0.338,0.637,1.002,1.825,1.403,respectively(χ2=41.05,P<0.05),the expression medians of TNF-α mRNA in liver were 0.140,0.254,0.372,0.399,0.699,respectively(χ2=38.16,P<0.05),the expression medians of HMGB1 mRNA in liver were 0.230,0.410,0.668,0.508,1.021,respectively(χ2=31.45,P<0.05).After infected with VV 48 hours for mice in A,B,C,D1,D2 group,the expression medians of nrf2 protein in liver were 0.908,1.461,2.061,3.982,2.243,respectively(χ2=33.72,P<0.05),the expression medians of IL-10 protein in liver were 13.97,22.54,30.14,57.98,41.53,respectively(χ2=37.31,P<0.05),the expression medians of TNF-α protein in liver were 114.07,142.94,175.44,174.60,266.11,respectively(χ2=32.29,P<0.05),the expression medians of HMGB1 protein in liver were 2.01,6.05,9.62,6.24,12.89,respectively(χ2=36.94,P<0.05).Compared with group A,there were large amount of fat drops,fatty changes in group B,inflammatory cell infiltration,disorder of hepatic cell in group C,and extension of hepatic duct and vein,edema of liver cells and disorder of hepatic cells in group D.Conclusion The nrf2 gene promoter of T336C mutation in C57B6 mouse of ALD can significantly decrease the expression of nrf2,and intensify organ inflammation and damage when they were infected by VV.     

Profiling of seminal antioxidant indices and sperm quality in Plasmodium bergheiinduced malarial mice treated with Phyllanthus amarus

Objective:To evaluate the antiplasmodial activity of Phyllanthus(P.)amarus crude ethanol leaf extract and its effects on semen quality in male BALB/c mice.Methods:A total of 36 adult mice were divided into six groups,with 6 mice each.Five groups were infected with Plasmodium(P.)berghei,and one group was left uninfeceted.Of the five infected groups,one group was left untreated,three groups were treated with varying doses(100,250 and 400 mg/kg)of P.amarus crude ethanol leaf extract orally for 4 days,and another group was treated with standard drug,artemether and lumefantrine(Lonart®DS).Antiplasmodial activity,seminal quality,some biochemical indices(neutral毩-glucosidase,fructose,and citric acid)in seminal plasma and seminal antioxidant markers(catalase,glutathione peroxidase,reduced glutathione,malondialdehyde,total antioxidant capacity,and acid phosphates)were determined.The mice were euthanized 3 days post treatment and semen was collected from the caudal epididymis and processed for analysis using documented methods and procedures.Results:Malarial infection led to oxidative stress,causing a significant decline in seminal quality(P<0.05).However,treatment with P.amarus crude ethanol leaf extract alleviated oxidative stress and significantly improved seminal quality.The improvement was dose-dependent and compared well with the standard drug,artemether and lumefantrine(Lonart®DS)treatment.Conclusions:The ethanol leaf extracts of P.amarus alleviate male reproductive capacity during malaria infection in murine model by enhancing antioxidant activities.     

拉米夫定联合还原型谷胱甘肽预防乙型肝炎病毒携带者抗结核的肝损害研究

Objective To explore the preventive effect of liver damage treated by lamivadine joint reduced glutathione for the tuberculosis patients with HBV infection. Methods 90 cases of tuberculosis patients with HBV infection were randomly divided into three groups (A, B, C), each group contained 30 cases. Patients in group A were treated by lamivudine combined with reduced glutathione to protect the liver before anti-tuberculosis treatment. Group B were treated with reduced glutathione. Group C were treated with Yiganling tablets. Both the liver function and serum HBV DNA levels before anti-tuberculosis treatment and 1 month and 2 months after treatment were observed and recorded. Results The cases of liver damage in group A, B, C were 1, 12, 18 respectively, there were statistical differences between group A and group B, group C (χ2 = 11.882, 22.259, P < 0.01). The cases of discontinued treatment due to different causes in group A,B,C were 0,4,11 respectively, there were statistical differences between group A and group B,group C(χ2 = 4.286, P < 0.05; χ2 = 13.469, P < 0.01). The cases of discontinue treatment in the no antivirus group were much more than the antivirus group. There were also statistical differences in both liver damage and discontinued treatment between group B and group C(χ2 = 5.455,4.356, P < 0.05). There was no statistical difference of baseline HBV DNA level between group A and group B (P > 0.05), and also no statistical difference between group A and group C ( P > 0.05), but there were statistical differences in HBV DNA level between group A and group B, as well as group A and group C after 1-month and 2-month therapy( t = - 6.542, - 6.746 and t = - 9.358, - 10.085, P < 0.01). Conclusions Tuberculosis patients coinfected with HBV can use reduced glutathione to prevent liver damage while antitubercular therapy, and simultaneous application of lamivudine therapy can restrain HBV replication and improve the prognosis obviously.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

Objective To investigate abnormal liver function associated with polymorphism of GSTT1,GSTM1 and CYP2E1 in workers exposed to N,N- dimethylformamide.Methods Sixty-nine workers with abnormal liver function in a synthetic leather factory were recruited as case.One hundred and twenty five control subjects with similar work tasks were selected from the same factory.Genotypes for GSTT1 and GSTM1 were determined by multiplex PCR,and for CYP2E1 PstI by PCR-RFLP assay.Results The frequency of positive GSTM1 was 59.42% in cases and 38.40% in control,with an odds ratio (OR) of 2.34,95% CI:1.29～4.29 (P=0.005).For GSTT1 and CYP2E1 PstI,the frequencies of genotypes showed no significant difference between case and control.Conclusion GSTM1 positive genotype may be genetic risk factors for development of abnormal liver function in workers exposed to N,N- diroethylformamide.     

三羟异黄酮保护急性酒精性肝损伤机制研究

目的探讨大豆三羟异黄酮(Gen)对急性酒精性肝损伤保护效果及与乙醇代谢相关酶活性的影响关系。方法 2 w龄昆明种小白鼠(90只)随机分为空白对照组,模型组,Gen试剂对照组(200 mg/kg bw),Gen试剂预防组(分别有50、100、200 mg/kg bw的低、中、高三种剂量,乙醇灌胃前给药)和Gen试剂治疗组(低、中、高三种剂量,乙醇灌胃后给药)9组;用50%乙醇12 ml/kg bw大剂量灌胃雄性小鼠诱发急性酒精性肝损伤,实验连续10 d后测定小鼠血液和肝脏组织的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、丙二醛(MDA)、甘油三酯(TG)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)等生化指标,测定肝脏组织的乙醇脱氢酶(ADH)、乙醛脱氢酶(ALDH)和细胞色素氧化酶系(CYP2E1)的活性。结果模型组小鼠血液与肝脏的ALT、AST水平比较空白对照组和Gen试剂对照组明显升高,差异显著(P<0.05=;Gen预防组与治疗组小鼠血液与肝脏的ALT、AST水平比较模型组显著降低,显示有剂量效应,MDA、TG比较模型组显著降低,GSH、SOD比较模型组显著升高,差异显著(P<0.05);Gen预防组与治疗组小鼠血液与肝脏的ADH、ALDH与模型组比较酶活性显著升高,CYP2E1酶活性显著降低;Gen对照组与空白对照组之间各项检测结果无显著差异。结论 Gen对急性酒精性肝损伤有预防保护效果,有影响乙醇代谢酶活性作用,缓解乙醇代谢产生的氧化应激。     

几种抗氧化剂拮抗染砷小鼠毒作用的实验研究

目的 :研究锌、维生素 C、维生素 E、二巯基化合物这几类抗氧化剂对砷染毒小鼠毒作用的拮抗作用。方法 :昆明种小鼠饮用含砷水同时通过灌胃给予不同种类的抗氧化剂 ,8周后 ,测定小鼠肝脏超氧化物岐化酶 (SOD)活性及丙二醛 (MDA)含量。结果 :干预后 ,与砷染毒对照组比较 :维生素 C组、维生素 E组、巯基组的 SOD活性升高 ,MDA含量下降 (P<0 .0 5 )。锌制剂组仅 SOD活性升高 ;与正常对照组比较 :维生素 C组、维生素 E组的 SOD活性和 MDA含量达到正常对照组水平 ,锌制剂组的 SOD活性与巯基组的 MDA含量分别达到正常对照组水平 (P>0 .0 5 )。结论 :一定剂量的锌制剂、维生素 C、维生素 E、二巯基化合物对砷染毒小鼠毒作用有拮抗作用。其中维生素 C、维生素 E的拮抗作用强 ,能完全纠正染砷小鼠的脂质过氧化的损伤 ,而锌制剂与二巯基化合物有一定的拮抗作用。     

姜精油对小鼠急性酒精性肝损伤的辅助保护作用

目的研究姜精油对小鼠急性酒精性肝损伤是否具有辅助保护作用。方法将70只BALB/C小鼠随机分为空白对照组,急性酒精性肝损伤模型组,姜精油超低剂量组(62.5mg/kg)、极低剂量组(125mg/kg)、低剂量组(250mg/kg)、中剂量组(500mg/kg)和高剂量组(1000mg/kg)7组,每组10只。常规喂养,每日灌胃给药1次,连续给药30天,第31天采用50%无水乙醇溶液进行一次性灌胃后断头处死。检测各组小鼠肝匀浆中的甘油三酯(TG)、丙二醛(MDA)和谷胱甘肽(GSH)水平,并进行肝脏病理组织学检查。结果随姜精油剂量的增加,小鼠肝组织匀浆的中TG值呈下降趋势,其中中剂量组和高剂量组与急性酒精性肝损伤模型组间存在显著差异(P<0.05);各剂量组的MDA值均明显低于急性酒精性肝损伤模型组(P<0.01),其中低剂量组的MDA值最低;极低剂量组和低剂量组的GSH值明显高于急性酒精性肝损伤模型组(P<0.05,P<0.01);低剂量组、中剂量组和高剂量组的肝脏病理组织检查评分明显低于急性酒精性肝损伤模型组(P<0.01)。结论姜精油对酒精性肝损伤具有辅助保护作用。     

Amelioration of ethanol-induced liver injury in rats by nanogold flakes

The purpose of this study was to investigate the protective effects of nanogold flakes against alcoholic liver disease. Six-week-old male Wistar rats were divided into 6 groups: C (control liquid diet), CLF (control liquid diet with gold flakes at 1.03 mg/kg body weight [BW]/day), CHF (control liquid diet with gold flakes at 5.15 mg/kg BW/day), E (ethanol liquid diet), ELF (ethanol liquid diet with gold flakes at 1.03 mg/kg BW/day), and EHF (ethanol liquid diet with gold flakes at 5.15 mg/kg BW/day). The liquid diets were prepared daily. Gold flakes were added to the ethanol 1 h before preparing the ethanol liquid diets, as an aging process. After 10 weeks, rats in group E showed significantly higher plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities than those in group C. A significantly increased concentration of hepatic triglyceride (TG) was found in group E. Furthermore, higher hepatic glutathione reductase (GRD), superoxide dismutase (SOD), and catalase (CAT) activities together with higher tumor necrosis factor (TNF)-α concentration and higher hepatic cytochrome (CYP2E1) protein expression were also observed in group E. In contrast, the hepatic TG concentration in group EHF was significantly lower than that of group E. In addition, hepatic glutathione peroxidase (GPX), SOD, and CAT activities together with TNF-α concentration and hepatic CYP2E1 protein expression in group EHF were significantly lower than those in group E. We concluded that nanogold flakes might ameliorate alcohol-induced liver injury by maintaining the hepatic antioxidative status. In addition, nanogold flakes may reduce fat accumulation caused by chronic ethanol feeding via decreasing hepatic TNF-α.     

大豆、枸杞子、山楂复合提取物对小鼠化学性肝损伤的保护作用

目的 :　研究大豆、枸杞子、山楂复合提取物对小鼠化学性肝损伤的保护作用。方法 :　设立空白对照、肝损伤对照和 0 .0 6、0 .2 0、0 .60 g/( kg· bw)复合提取物五组 ,分别建立小鼠CCl4 肝损伤模型和乙醇肝损伤模型 ,4w后 ,前者测定血清中丙氨酸氨基转移酶 ( ALT)及天门冬氨酸氨基转移酶 ( AST)活性 ,同时观察肝脏组织病理 ;后者测定肝匀浆中丙二醛 ( MDA)、谷胱甘肽( GSH)和甘油三酯 ( TG)含量 ,同时观察肝脏病理。结果 :　 CCl4 肝损伤模型 :复合提取物中剂量组的血清 ALT及中、高剂量组的血清 AST水平均较 CCl4 对照组降低 ,低剂量组发生肝细胞坏死和中、高剂量组发生炎症细胞浸润的程度明显较 CCl4 对照组轻。乙醇肝损伤模型 :低、高剂量组MDA和各剂量组 TG含量以及低、中剂量组脂肪变性评分均明显低于乙醇对照组。结论 :　大豆、枸杞子、山楂复合提取物对 CCl4 和乙醇诱导的小鼠化学性肝损伤有保护作用。     

枳实提取物对实验性糖尿病小鼠肝脏抗氧化防御功能的影响

目的研究枳实提取物对试验性糖尿病小鼠肝脏抗氧化能力的影响。方法用高、中、低剂量的枳实提取物治疗糖尿病小鼠5周后,观察其一般状况、肝脏的抗氧化能力及肝脏组织形态学变化。结果枳实提取物治疗组,与糖尿病模型组比较,血糖水平显著降低(P<0.05),谷胱甘肽含量(GSH)显著增加(P<0.05),谷胱甘肽过氧化物酶活性、丙二醛和NO含量显著降低(P<0.01),超过氧化物歧化酶活性有所增加。光镜下枳实提取物治疗组肝组织细胞损伤较糖尿病组降低。结论枳实提取物具有增强肝脏的抗氧化能力,降低肝细胞损伤作用。     

茵陈蒿汤对代谢综合征-脂肪肝大鼠增强胰岛素敏感性及抗脂肪肝作用

目的观察茵陈蒿汤(capillaris decoction)对高脂-高糖诱导代谢综合征(metabolic syndrome,MetS)-脂肪肝(fattyliver,FL)大鼠的防治作用及机制。方法 SD大鼠,雌雄各半,除空白对照组食用标准饲料和饮用蒸馏水外,其余动物随机喂饲富含高脂肪(25%)饲料和高蔗糖(10%)饮水,造模8周;然后将大鼠随机分为模型对照、silibinin150mg.kg-1以及茵陈蒿汤5.0g.kg-1及2.5g.kg-1两个剂量组;分别灌胃给药或蒸馏水,qd×4w,测定大鼠空腹血清胰岛素(Fins)、血糖(FBG)、三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、脂联素,天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱酯酶(ChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)和一氧化氮(NO),并计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(IRI)及肝指数;光学显微镜下观察肝脏组织的病理学改变。结果 MetS-FL大鼠TC、FFA、TG、LDL-C、MDA、FBG和Fins含量升高,HDL-C、NO和脂联素含量下降,AST、ALT、ChE活性升高,NOS和SOD活性降低,ISI减弱,肝指数升高并呈脂肪肝组织病理改变,与正常对照组比较,差异有显著性(P<0.05或P<0.01)。茵陈蒿汤5.0g.kg-1及2.5g.kg-1以及silibinin150mg.kg-1处理MetS-FL大鼠后,不同程度地降低MetS-FL大鼠TC、FFA、TG、LDL-C、MDA、FBG、Fins含量和AST、ALT、ChE活性,升高HDL-C、NO和脂联素含量,增强ISI,肝指数下降并改善脂肪肝组织病理改变,差异有显著性(P<0.05或P<0.01)。结论茵陈蒿汤对抗MetS-FL大鼠IR、增强胰岛素敏感性、纠正高胰岛素血症,改善血糖-脂代谢紊乱,抑制氧化应激反应和肝细胞损伤,降低氨基转移酶和ChE活性,以及不同程度地改善脂肪肝组织的病理改变,是茵陈蒿汤拮抗代谢综合征-脂肪肝的部分作用机制。茵陈蒿汤抗脂肪肝效应显示量效关系。     

银杏叶提取物预防大鼠酒精性肝损伤的机制研究

目的:观察银杏叶提取物(EGB)对大鼠酒精性肝损伤的预防作用,并研究其可能的分子机制。方法:无水乙醇灌胃13w,EGB采用预防性给药的方法,检测大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)活性;肝组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和谷胱甘肽(GSH)、丙二醛(MDA)的含量;采用RT-PCR检测肝组织中血红素氧化酶-1(HO-1)mRNA表达水平。结果:与酒精组相比,EGB组ALT、AST活性均显著降低(P<0.05),MDA含量非常显著降低(P<0.01);SOD、GSH-Px活性和GSH含量较酒精组均显著升高(P<0.05);此外,EGB可以诱导HO-1mRNA高表达。结论:EGB通过减少酒精所致GSH的耗竭,增加抗氧化物质活性或含量,抑制脂质过氧化反应从而预防酒精性肝损伤,其机制可能与诱导HO-1表达有关。     

Gender-related differences in mouse hepatic ethanol metabolism

The effect of an acute oral load of 2 g ethanol/kg body weight was studied in a group of male and female 10-wk-old C3H/HeNCrj (C3H/He) mice to investigate gender change throughout differences of the hepatic ethanol metabolism of mice. The following parameters were measured in the serum from 0 h to 3 h after the start of the experiment: ethanol, acetaldehyde, and acetate. Their concentrations in the serum in female mice tended to show lower levels than in male mice. In female mice, the concentration of ethanol at 1 h and the concentration of acetate at 1 h, 2 h, and 3 h after ethanol administration showed significantly lower levels than in male mice. Ten-week-old male and female C3H/He mice were subcutaneously injected 50 microg/kg body weight beta-estradiol and 1.45 mmol/kg body weight testosterone propionate (testosterone) in olive oil, respectively, and changes in the activity of enzymes related to the hepatic ethanol metabolism of mice were examined at 24 h after the administration of sex hormones. The activity of the cytosolic alcohol dehydrogenase (ADH) and microsomal aniline hydroxylase (ANH) and the low Km, high Km and total aldehyde dehydrogenase (AlDH) activities in the mitochondrial, the cytosolic, and the microsomal fraction of the liver were higher. Moreover, the density of the band of CYP2E1 in the microsome in female mice was stronger than in male mice, and in the microsomal fraction of the liver, the total content of cytochrome P-450 (CYP) and ethoxyresorufin O-dealkylase (EROD) activity in male mice showed significantly higher values than in female mice. The density of the band of CYP2E1 and the three activities of AlDH in the hepatic mitochondrial fraction of male mice increased significantly under treatment with beta-estradiol. The three activities of AlDH of the cytosolic fraction of the liver in female mice significantly decreased under treatment with testosterone. The present findings suggested that in C3H/He mice livers, the rate of ethanol metabolism is faster in females than in males, and the enzymes related to ethanol metabolism are controlled by testosterone or beta-estradiol. It is suggested that ethanol and its metabolite disappear faster from the serum of female mice than from the serum of male mice because the activities of hepatic enzymes related to ethanol metabolism are higher in female mice than in male mice. C3H/He mice, hepatic ethanol metabolism, gender different, ADH, AlDH     

维生素Ｅ对1，2-二氯乙烷中毒性脑水肿保护作用的研究

目的探讨维生素E (vitamin E,Vit E)对1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒性脑水肿的保护作用。方法将雌性昆明种小鼠随机分为空白对照组、Vit E对照组、1,2-DCE单纯染毒组及Vit E低、中和高剂量干预组。连续给予药物灌胃4 d后,采取静式吸入方式染毒3. 5 h/d,持续3 d。结果与空白对照组相比,单纯染毒组小鼠脑组织呈现明显脑水肿病理改变,脑含水量、脑组织中丙二醛(malondialdehyde,MDA)含量及细胞色素P450 2E1 (cytochrome P450 2E1,CYP2E1)蛋白和mRNA表达水平显著升高,脑组织中还原型谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase assay kit,CAT)活性、Occludin蛋白和mRNA及Claudin 5蛋白表达水平显著降低。与单纯染毒组相比,各干预组小鼠的脑含水量、脑组织MDA含量、CYP2E1蛋白和mRNA表达水平显著降低,GSH含量、Occludin蛋白及mRNA水平显著升高;中和高剂量干预组的小鼠脑组织中SOD和CAT活性及Claudin 5蛋白表达水平亦显著升高(P0. 05)。结论单纯1,2-DCE染毒可引起小鼠脑水肿,诱导脑组织中CYP2E1的表达,诱发脑组织氧化损伤,破坏紧密连接蛋白,并抑制Occludin和Claudin 5的表达;而Vit E干预可显著抑制CYP2E1的表达,缓解CYP2E1介导的氧化损伤,有效预防1,2-DCE引起的中毒性脑水肿。