还原型谷胱甘肽治疗药物性肝损伤的疗效观察

目的观察还原型谷胱甘肽(GSH)对药物性肝损伤(drug-indnced liver injury DILI)的疗效,进而探讨作用机制.方法 74例药物性肝损伤患者随即分为治疗组(37例)和对照组(37例),两组均采用常规护肝治疗,治疗组在护肝治疗基础上GSH1.8g静脉滴注,每日1次,治疗4周.观察两组治疗前后临床症状,体征、实验室检查指标的变化.结果 治疗组患者的各项观察指标是优于对照组,两组效果差异具有统计学意义.结论 治疗组还原型谷胱甘肽对治疗药物性肝损伤疗效显著,其作用机制为通过抗氧化作用,减轻肝细胞线粒体损伤,从而促进肝细胞修复及肝功能恢复.     

还原型谷胱甘肽的临床应用

谷胱甘肽是人类细胞中自然合成的一种肽，还原型谷胱甘肽（CSH）是主要的活性状态，GSH作为细胞内的自然抗氧化剂发挥作用，病理状态下的内源性GSH减少时，适时补充外源性GSH可以预防、减轻、中止组织细胞的损伤。近年来，随着GSH的临床应用日益广泛，在各种原因引起的肝肾损害，对肿瘤患者的辅助治疗、糖尿病肾病、急性酒精中毒、帕金森病等疾病的治疗中，都取得了较好的临床疗效，随着GSH研究的逐步深入，其在临床应用方面必将取得更进一步的发展。     

谷胱甘肽对内毒素致大鼠急性肺损伤的保护作用

目的 观察谷胱甘肽(GSH)在急性肺损伤(ALI)治疗中的保护作用,并探讨损伤与凋亡相关基因bcl-2及fas的可能机制.方法 动物随机分对照组、损伤纽、还原型谷胱甘肽干预组,每组6只;对照组及损伤组分别从股静脉注射生理盐水及脂多糖(LPS),并于注射前及后30,60,120 min时采集血样及肺组织样品;还原型谷胱甘肽干预组:注射LPS前1 h、即刻及后30 min股静脉注射还原型谷胱甘肽,余同内毒素组.检测各肺损伤指标,观察病理形态并作免疫组化染色.结果 各项指标干预组均较损伤组减轻;且越早应用GSH对肺脏的保护作用越强;肺组织匀浆中的GSH含量增高(P＜0.01).正常肺组织bcl-2及fas均有基础低表达,LPS致伤后较正常组表达增高,经GSH处理后表达减弱.结论 谷胱甘肽可能通过诱导bcl-2基因表达增高(P＜0.01)及抑制fas基因使其表达减少(P＜0.05),从而逆转凋亡,保护肺组织.     

还原型谷胱甘肽在重型肝炎治疗中的作用

目的 :探讨还原型谷胱甘肽 (GSH)抗氧自由基作用在重型肝炎治疗中的应用价值及地位。方法 :52例重型肝炎患者随机分成两组 :GSH治疗组和非GSH治疗组 ,每组 2 6例 ,观察两组在临床症状、体征、肝功能 ,血清总胆红素 (TBIL)及凝血酶原活动度 (PTA)的改善情况 ,并进行统计学处理。结果 :GSH治疗组出院好转率明显高于非GSH治疗组 (P <0 .0 5)。治疗 6周后 ,GSH治疗组的TBIL及PTA均值较本组治疗前的TBIL及PTA均值有显著改善 ,基本达到控制病情的目的 ,而非GSH治疗组的TBIL及PTA均值在治疗前后无改善 ,病情未得到控制。结论 :还原型谷胱甘肽的抗氧自由基作用在治疗重型肝炎中有重要的临床应用价值。     

还原型谷胱甘肽合用粉防己碱对帕金森病大鼠脑线粒体酶复合体I及活性氧的影响

目的 观察还原型谷胱甘肽(GSH)合用粉防己碱(Tet)对帕金森病(PD)大鼠氧化应激水平的影响并探讨其作用机制.方法 应用6-羟基多巴立体定向注射制作PD大鼠模型,将成功大鼠模型随机分为模型组、GSH组、GSH Tet组、左旋多巴组,另设正常对照组,给药50d后测定鼠脑黑质线粒体酶复合体I活性及纹状体活性氧(ROS)含量.结果 GSH Tet对PD大鼠黑质线粒体酶复合体I有保护作用,GSH Tet能明显降低PD大鼠纹状体活性氧(ROS)水平.结论 GSH Tet能减轻PD大鼠黑质及纹状体氧化应激损伤,并对线粒体呼吸链有一定保护作用.     

还原型谷胱甘肽保护线粒体并减轻大鼠肝脏缺血再灌注损伤

【】 目的 探讨还原型谷胱甘肽(GSH)减轻肝脏缺血再灌注(IR)损伤的作用及机制。方法 将成年SD大鼠分为假手术组、I/R组和GSH组。除假手术组外,其余组建立70%大鼠肝IR损伤模型,肝脏缺血时间为60 min。GSH组于缺血前5 min经大鼠股静脉注射5mg/kg的GSH。再灌注24h后通过血清学和组织学指标观察肝损伤情况,TUNEL染色评价肝细胞凋亡。比较各组组织GSH/GSSG率,检测各组肝细胞线粒体钙容纳力(CRC)。结果 与I/R组比较,再灌注后GSH组血清AST和ALT均明显降低(P＜0.05)。再灌注24 h,与I/R组比较, GSH组肝组织损伤明显减轻,凋亡细胞数显著减少(P＜0.05);同时,肝组织GSH/GSSG比值明显增加(P＜0.05);再灌注后24 h,与I/R组比较,GSH组肝细胞线粒体钙容纳力明显增加。结论 GSH预处理能减轻大鼠肝脏I/R损伤,该作用可能与减少氧化应激,从而抑制mPTP开放有关。     

还原型谷胱甘肽引起肝损伤68例疗效观察

肝损伤是肺结核病人应用抗结核药物治疗过程中常见的不良反应。目前临床上对抗结核药物引起的肝损伤预防多采用初期联合口服肌酐片、维生素等,但疗效不好。还原型谷胱甘肽（GSH）可以改善药物性肝损伤,促进受损的肝细胞修复。我们应用GSH治疗抗结核药物导致的药物性肝损伤，取得良好效果，现报告如下。     

肝细胞刺激因子对环磷酰胺致小鼠肝细胞损伤的保护作用

目的 研究环磷酰胺(CTX)对肝细胞的损伤及肝细胞刺激因子(HSS)对该损伤的保护作用。方法 应用原代小鼠肝细胞混悬培养，检测肝细胞培养液中乳酸脱氢酶(LDH)活性和肝细胞谷胱甘肽(GSH)、丙二醛(MDA)含量变化。结果 CTX可使LDH漏出增多，同时肝细胞GSH含量减少，MDA含量增加，HSS可部分逆转上述变化。结论 CTX可致肝细胞损伤，HSS降低肝细胞MDA含量可能是其保肝机制之一。     

还原型谷胱甘肽在抗结核药物引起的肝损害中的应用

本文就还原型谷胱甘肽治疗抗结核药物引起肝损害进行论述。还原型谷胱甘肽对防止肝细胞的破坏、保护肝细胞、清除自由基有非常重要的作用,并通过还原型谷胱甘肽与复方甘草酸单胺、肝太乐以及单用还原型谷胱甘肽等保肝治疗之比较研究,证明还原型谷胱甘肽在抗结核药引起的肝损害中疗效确切。     

72小时睡眠剥夺大鼠的氧化应激

目的 观察72h睡眠剥夺大鼠的氧化应激状态。方法 参照Everson等的方法，将SD大鼠予以72h剥夺睡眠处理后，断头取血，比色法测定血浆丙二醛(MDA)和还原型谷胱甘肽(GSH)的含量以及谷胱甘肽过氧化物酶(GSH—Px)、谷胱甘肽还原酶(GSH—R)和超氧化物岐化酶(SOD)的活性。结果 与对照组相比，睡眠剥夺大鼠血浆MDA的含量增高，GSH含量降低，GSH—Px和GSH—R活性降低，SOD活性有降低趋势。结论 72h睡眠剥夺大鼠处于氧化应激状态，氧化应激可能是睡眠剥夺引起病理变化的机制之一。     

Exposure to static magnetic field of pregnant rats induces hepatic GSH elevation but not oxidative DNA damage in liver and kidney

BACKGROUND: The present investigation was designed to evaluate the effects of subacute exposure to static magnetic field (SMF) on some parameters indicative of oxidative stress and on oxidative DNA damage in pregnant rat. METHODS: Females rats (n = 6) were exposed to a SMF (128 mT; 1 h/day) from day 6 to day 19 of pregnancy and were allowed to deliver normally. The control group (n = 6) was not exposed to SMF. Dams were sacrificed 3 days after delivery. The effects of subacute exposure to SMF on oxidative states were assessed on the measurements of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH) and catalase (CAT). The level of 8-oxo-dG was measured using high-performance liquid chromatography coupled to electrochemical detection. RESULTS: Subacute exposure to SMF failed to alter plasma GPx, MDA, CAT and SOD respectively in liver and kidney. By contrast, SMF increased total GSH (+56%, p <0.05) and reduced GSH (+108%, p <0.05) in liver. Our results showed that the exposure to SMF did not induce oxidative DNA lesions in liver and kidney. CONCLUSIONS: The data do not provide evidence that subacute SMF exposure causes DNA damage in liver and kidney in pregnant rats. The present results suggest that hepatic GSH plays an important role in protection against SMF during pregnancy. These changes in antioxidant status (GSH) lead to some adaptive responses due to activation of systems controlling the body oxidative mechanism balance.     

单壁碳纳米管的肺毒性及氧化应激机制

目的 研究单壁碳纳米管(single-wall carbon nanotubes,SWCNTs)的肺毒性,并探讨其毒性机制,为安全生产和应用SWCNTs提供实验依据.方法 A549细胞用质量浓度为0、25、50、100、150、200 μg/mL的SWCNTs溶液孵育24 h,用CCK-8和乳酸脱氢酶(lactate dehydrogenase,LDH)试剂盒分别检测SWCNTs对A549细胞活性和细胞膜的影响,Hoechst 33342和PI荧光双染法检测细胞死亡情况,透射电镜(TEM)观察细胞超微结构变化,并检测细胞内活性氧(reactive oxygen species,ROS)水平、谷胱甘肽(glutathione,GSH)浓度和超氧化物歧化酶(superoxide dismutase,SOD)活力以评估氧化应激情况.分别将0.5 mg/mL和1 mg/mL的SWCNTs溶液通过气管灌流的方法使大鼠肺部染毒,3d后取大鼠肺脏,常规H-E染色,检测肺组织病理学变化.结果SWCNTs对A549细胞表现出明显毒性,使细胞活性降低,死亡细胞增多,细胞膜和细胞结构损伤严重,细胞内ROS水平升高,GSH浓度和SOD活力降低.体内毒性检测结果表明SWCNTs在大鼠肺组织内积累,造成肺泡壁水肿增厚.结论 体外细胞毒性检测和动物毒性检测结果表明SWCNTs具有较大的肺毒性,其主要毒性机制是氧化应激反应.     

Chelation therapy with desferrioxamine does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients

Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in beta-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.     

Lead Induced Oxidative Stress： Beneficial Effects of Kombucha Tea

Objective To evaluate the effect of oral administration of Kombucha tea (K-tea) on lead induced oxidative stress. Methods Sprague Dawley rats were administered 1mL of 3.8% lead acetate solution daily alone or in combination with K-tea orally for 45d, and the antioxidant status and lipid peroxidation were evaluated. Results Oral administration of lead acetate to rats enhanced lipid peroxidation and release of creatine phosphokinase and decreased levels of reduced glutathione (GSH) and andoxidant enzymes (superoxide dismutase, SOD and glutathione peroxidase, GPx). Lead treatment did not alter humoral immunity, but inhibited DTH response when compared to the control.Lead administration also increased DNA fragmentation in liver. Oral administration of Kombucha tea to rats exposed to lead decreased lipid peroxidation and DNA damage with a concomitant increase in the reduced glutathione level and GPx activity. Kombucha tea supplementation relieved the lead induced immunosuppression to appreciable levels. Conclusion The results suggest that K-tea has potent antioxidant and immunomodulating properties.     

顺势疗法药物山金车30C通过上调核苷酸切除修复基因的表达减少紫外线照射后大肠杆菌的DNA损伤

目的：检测高度稀释的顺势疗法药物山金车30C是否能够调节暴露于紫外线照射下的大肠杆菌的核苷酸切除修复基因的表达。方法：大肠杆菌在标准培养基中培养至对数阶段,然后接受亚致死剂量的紫外线照射（25和50J／m。分别照射22．5和45s）。接受不同剂量紫外线照射的大肠杆菌分别与山金车30C及安慰剂30C共同培养,90min后检测其DNA损伤情况及氧化应激状态。采用多种方法及指标如彗星实验、梯度凝胶电泳、细胞内活性氧生成及测量其他生物活性指标如过氧化物歧化酶、过氧化氢酶及谷胱甘肽衡量DNA损伤情况及细胞氧化应激状态。逆转录聚合酶链反应检测大肠杆菌细胞紫外线损伤修复基因uvrA、B、c（核苷酸切除修复基因）mRNA的表达情况。结果：接受照射后的大肠杆菌出现了DNA损伤及氧化应激反应,表现为细胞内活性氧生成增加及过氧化物歧化酶、过氧化氢酶和谷胱甘肽活性降低。与安慰剂组相比,山金车30C降低了大肠杆菌的DNA损伤及氧化应激反应,表现为细胞内活性氧生成减少及过氧化物歧化酶、过氧化氢酶和谷胱甘肽活性增强。与对照组相比,山金车30C上调了大肠杆菌细胞紫外线损伤修复基因的表达。结论：山金车30C能够通过上调紫外线损伤修复基因的表达修复紫外线引起的大肠杆菌细胞的DNA损伤,并通过减少细胞内活性氧的生成及调节抗氧化酶活性降低细胞的氧化应激反应。     

根皮素抑制LPS诱导的BV2小胶质细胞氧化应激反应

目的 探讨根皮素(phloretin, PHL)对脂多糖(lipopolysaccharide, LPS)导致的BV2小胶质细胞的氧化应激损伤的抑制作用及可能的分子机制。方法 利用LPS建立BV2小胶质细胞的氧化应激损伤模型,对该模型予以不同浓度的PHL 预处理。利用MTS方法检测细胞活力。ELISA法检测氧化应激相关产物一氧化氮(nitric oxide,NO)、丙二醛(malondialdehyde,MDA)、谷胱甘肽(glutathione,GSH)含量及超氧化物歧化酶(superoxide dismutase,SOD)的活性。双荧光素酶活性检验方法检测抗氧化响应元件荧光素酶报告基因质粒(antioxidant reaction element luciferase reporter plasmid,ARE-LUC)报告基因转录活性。Western blotting法检测磷酸化核因子-E2相关因子2(nuclear factor E2-related factor 2,Nrf2)和血红蛋白加氧酶-1(heme oxygenase-1,HO-1)蛋白表达。结果 与对照组相比,LPS处理后的BV2小胶质细胞活力显著降低,氧化应激产物NO和MDA水平明显升高,GSH含量和SOD活性明显下降,但Nrf2磷酸化水平、ARE-LUC报告基因转录活性和HO-1蛋白表达略有增高。与模型组比较,高剂量PHL(20 μmol/L)预处理明显改善了LPS导致的BV2小胶质细胞活力下降,降低NO和MDA的含量,增高GSH的含量和SOD的活性,且进一步增加了Nrf2的磷酸化水平,上调ARE-LUC的转录活性和HO-1蛋白的表达。结论 PHL可以显著抑制LPS导致的BV2小胶质细胞的氧化应激损伤,Nrf2/ARE通路可能是根皮素发挥抑制BV2小胶质细胞氧化应激损伤作用的途径之一。     

Elevated peroxidative glutathione redox status in atherosclerotic patients with increased thickness of carotid intima media

Background Atherosclerosis is a chronic inflammatory disease. Accumulated evidences suggest a deep involvement of oxidative damage in the development of atherosclerosis, but little is discussed over the relationship between plasma glutathione redox status as the most important intrinsic antioxidant defensive mechanism and the atherosclerosis. Methods A total of 132 patients suspected with atherosclerosis were assigned to three groups by high frequency ultrasonic examination of the carotid artery. With the thickness of intima of the carotid artery as an index of degree of atherosclerosis progression, 56 were included in plaque-forming group （A）, 42 in carotid artery intima-thickening group （B）, and 34 in normal carotid artery intima-thickness group （C）. All patients were subjected to the measurement of plasma glutathione （GSH） （reduced form GSH and oxidized form GSSG）, nicotinamide adenine dinucleotide phosphate （NADP） （reduced form NADPH and oxidized form NADP^＋）, oxidized low density lipoprotein （oxLDL）, and malondialdehyde （MDA） The GSH/GSSG and NADPH/NADP^＋ redox potentials were calculated according to the Nernst equation, and their correlation with intima thickness and oxLDL was analyzed. Results With the thickening of artery intima （from group C to A）, GSH concentration and the ratio of GSH/GSSG gradually reduced, and GSSG and GSH/GSSG redox potential gradually increased （more positive） （P 〈0.05）. The NADPH and NADPH/NADP^＋ redox status also showed similar but milder changes. The products of oxidative stress oxLDL and MDA increased significantly along with the thickening of artery intima （P 〈0.05）. The analysis of the relationship between GSH/GSSG redox potential, intima thickness, and oxLDL showed positive correlations （P 〈0.05）. The plasma GSH/GSSG redox status was positively correlated with the intima thickness of the carotid artery and the oxidized injury of LDL. The redox status shifted to oxidizing direction along with the intima thickening and plaque-forming. Conclusion Elevated peroxidative glutathione redox status was deeply implicated in atherosclerosis progressing, and it may be a sensitive and reliable index for monitoring oxidative status in atherosclerosis.     

HPLC法同时检测血浆中半胱氨酸/胱氨酸和还原型谷胱甘肽/氧化型谷胱甘肽的氧化还原电势

目的本研究拟探讨一种比较敏感、能同时检测血浆中半胱氨酸(cysteine,Cys)/胱氨酸(cystine,CySS)和还原型谷胱甘肽(reduced glutathione,GSH)/氧化型谷胱甘肽(oxidized glutathione,GSSG)含量及相应的氧化还原电势(Eh)的方法。方法取大鼠全血,去除红细胞及蛋白后用碘乙酸封闭自由的巯基,通过丹磺酰氯衍生化后,利用高效液相色谱(highperformance liquid chromatography,HPLC)进行分离,根据能斯特方程计算相应的氧化还原电势。结果本方法可同时测定体内GSH/GSSG和Cys/CySS的含量及相应的氧化还原电势,灵敏度高、准确性强。结论本研究提供了一种简便有效地检测血浆中氧化还原状态的方法,可能为诊断与氧化应激相关疾病提供新的依据。     

阿拓莫兰对儿童肝损害多项指标及病程影响的临床观察

目的:观察阿拓莫兰(还原型谷胱甘肽)对儿童肝损害多项指标及病程的影响。方法:应用阿拓莫兰治疗儿童肝损害89例,对照组83例。观察其对肝损害多项指标及病程的影响。结果:疗程结束后两组患者的谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、白蛋白(ALB)和胆红素(TBI)均较治疗前有明显改善;治疗后两组患者在乏力的改变方面有显著性差异,在食欲不振、腹胀、肝区叩击痛的改善方面有非常显著性差异;治疗结束后两组患者食欲不振、腹胀、肝区叩击痛及肝压痛的总改善率也有非常显著性差异。结论:阿拓莫兰对儿童肝病症状、体征及肝功能指标改善效果好,疗程短,速度快,同时对伴有高脂血症的患者具有降低血脂的作用。值得作为一种常规儿童肝损害药物在临床中应用。