N-乙酰半胱氨酸对体外循环所致大鼠肺损伤的影响及机制研究

目的 探讨N-乙酰半胱氨酸(N-acetyl cysteine, NAC)对体外循环(Cardiopulmonary bypass, CPB)所致大鼠肺损伤的影响及可能机制。方法 将24只清洁级健康成年雄性SD大鼠按随机数字表法分为假手术组(Control组)、CPB组、NAC+CPB组,每组各8只。观察各组大鼠肺组织病理学变化并进行肺损伤评分。采用酶联免疫吸附法检测肺组织中肿瘤坏死因子(TNF-α)、白细胞介素(IL-6)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平。采用蛋白免疫印迹法检测肺组织紧密连接蛋白claudin-4的表达情况。结果 光镜下,Control组肺组织结构清晰完整,未见明显异常,CPB组和NAC+CPB组大鼠的肺泡、肺泡腔、肺泡间隔均有不同程度的损伤。CPB组和NAC+CPB组的肺损伤评分、湿/干重比值、呼吸指数(RI)、TNF-α、IL-6、MDA高于Control组,且NAC+CPB组均低于CPB组,差异有统计学意义(P<0.05)。CPB组和NAC+CPB组氧合指数(OI)、SOD低于Control组,且NAC+CPB组高于CPB组,差异均有统计学...     

N-乙酰半胱氨酸对糖尿病模型小鼠氧化应激的影响研究

目的:探讨N-乙酰半胱氨酸(NAC)对糖尿病模型小鼠氧化应激的影响。方法:取小鼠腹腔注射链脲佐菌素建立糖尿病模型,建模成功8周后随机分为非治疗组和NAC治疗组(200mg·kg-1.d-1),每组6只,腹腔注射相应药物,每日1次,连续4周,另设正常对照组进行比较。检测各组小鼠给药前后体重、血糖水平及给药后尿液中脂质过氧化标志物8-异前列腺素(8-Isoprostane)浓度。结果:与正常对照组比较,非治疗组和NAC治疗组小鼠给药前后体重均明显降低,血糖均明显升高(P<0.001),但2组间比较无显著性差异;与非治疗组比较,NAC治疗组小鼠尿液中8-Isoprostane浓度明显降低(P<0.01),且与正常对照组比较无显著性差异。结论:NAC可有效改善糖尿病模型小鼠的氧化应激状态。     

N-乙酰半胱氨酸对急性坏死性胰腺炎肺损伤的治疗作用

目的 通过分析急性坏死性胰腺炎时肺中IL-18,IL-8,MPO的表达及血清钙的水平,研究N-乙酰半胱氨酸(NAC)对肺损伤的保护作用.方法 使用随机数字表将72只Wistar大鼠分成3组,分别为对照组(ANP组),治疗组(NAC组),假手术组(SO组).6 h,12 h,18 h取各组大鼠胰及肺组织、静脉血供实验用.免疫组化法测定肺中IL-18,IL-8的表达;比色法测定肺中MPO的水平;胰、肺组织在光镜下行病理学检查.结果 ANP组肺组织IL-18,IL-8,MPO的水平随时间升高,同时血钙浓度降低,与SO组相比各时间点均有显著差异.NAC组IL-18,IL-8在各时间点均显著低于ANP组,MPO在12 h时降低,血钙浓度各时点均明显升高.结论 发生ANP后,肺组织中 IL-18、IL-8、MPO水平升高,血清钙降低,炎症加重.NAC能够抑制炎症因子的表达,减轻肺损伤.     

N-乙酰半胱氨酸在急性肺损伤中的保护作用

目的观察N-乙酰半胱氨酸(NAC)在急性肺损伤(ALI)中的保护作用。方法建立脂多糖(LPS)诱导的大鼠急性肺损伤模型,将24只大鼠随机分为空白对照组、LPS组和NAC组,测定各组肺含水量、湿/干质量比值,对支气管肺泡灌洗液(BALF)中白细胞计数,并用ELISA法测定肿瘤坏死因子(TNF-α)的量。结果NAC组大鼠肺含水量、湿/干质量比值、TNF-α含量、白细胞计数均少于LPS组(P<0.05)。结论N-乙酰半胱氨酸能通过阻断细胞因子和炎性介质的释放来抑制大鼠急性肺损伤的肺部炎症反应。     

N-乙酰半胱氨酸对急性肺损伤大鼠环氧合酶-2的影响

目的:探讨N-乙酰半胱氨酸(NAC)对急性肺损伤(ALI)大鼠环氧合酶-2(COX-2)的影响,进一步研究N-乙酰半胱氨酸对急性肺损伤(ALI)肺组织的保护作用。方法:应用脂多糖(LPS)诱导大鼠急性肺损伤(ALI)模型,然后应用N-乙酰半胱氨酸进行干预。实验设对照组、模型组、N-乙酰半胱氨酸组,在肺损伤模型成功后24 h处死大鼠,取左叶肺组织。采用免疫组化染色,检测N-乙酰半胱氨酸对急性肺损伤大鼠肺组织中COX-2的表达,利用HPIAS-2000图像分析系统测定COX-2在以上各组中表达的平均光密度和平均阳性面积率。结果:实验对照组肺组织中COX-2的表达较低;模型组肺组织中COX-2的表达高;N-乙酰半胱氨酸组肺组织中COX-2表达较低。经q检验,实验对照组与模型组之间,COX-2的平均光密度及阳性面积率有显著性差异(P<0.01?,实验对照组与N-乙酰半胱氨酸组之间,COX-2的平均光密度及阳性面积率差异无显著性(P>0.05)。结论:N-乙酰半胱氨酸可以减轻肺损伤的程度,对急性肺损伤组织具有重要的保护作用。     

N-乙酰半胱氨酸对急性肺损伤大鼠肺组织水通道蛋白表达的研究

目的:观察N-乙酰半胱氨酸(NAC)对急性肺损伤(ALI)肺组织水通道蛋白-1的表达,进一步探讨N-乙酰半胱氨酸对急性肺损伤(ALI)肺组织的保护作用。方法:应用脂多糖(LPS)诱导大鼠急性肺损伤(ALI)模型,然后应用N-乙酰半胱氨酸进行干预。实验设对照组、模型组、N-乙酰半胱氨酸组,在肺损伤模型成功后24 h处死大鼠,取左叶肺组织。采用免疫组化染色,检测N-乙酰半胱氨酸对急性肺损伤大鼠肺组织中水通道蛋白-1(AQP-1)的表达,利用HPIAS-2000图像分析系统测定水通道蛋白-1在以上各组中表达的平均光密度和平均阳性面积率。结果:实验对照组肺组织表达高水平AQP-1;模型组肺组织呈浅黄色染色,AQP-1表达较低;N-乙酰半胱氨酸组肺组织表达高水平AQP-1。经q检验,实验对照组与模型组之间,AQP-1的平均光密度及阳性面积率有显著性差异(P<0.01?,实验对照组与N-乙酰半胱氨酸组之间,AQP-1的平均光密度及阳性面积率差异无显著性(P>0.05)。结论:N-乙酰半胱氨酸能使急性肺损伤组织中AQP-1呈高表达,对急性肺损伤组织有重要的保护作用。     

N-乙酰半胱氨酸对甲基苯丙胺中毒大鼠行为改变的影响

目的:探讨N-乙酰半胱氨酸(NAC)对甲基苯丙胺(METH)引起中毒大鼠模型行为改变的保护性作用机制。方法:制备大鼠中毒模型,在METH注射前30min腹腔注射NAC,应用二氯荧光乙酰乙酸盐(DCFH)作为荧光指标检测大鼠纹状体ROS的含量,以紫外分光光度计检测NOS的活性,以Sams-Dodd的方法给大鼠刻板行为评分,并计算不同组大鼠评分之间的差异。结果:NAC预处理能降低纹状体内ROS的含量(P<0.001)及NOS的活性(P<0.001),减轻METH中毒大鼠精神行为改变,降低了中毒大鼠的刻板行为评分(P<0.001)。结论:NAC可能通过逆转METH诱导大鼠纹状体区的氧化失衡状态,减轻氧化应激诱导的精神行为异常改变,产生保护性作用。     

N-乙酰半胱氨酸在呼吸系统疾病中的应用

目的:评价N-乙酰半胱氨酸(NAC)在呼吸系统疾病中的应用。方法:通过查阅国外近期相关文献进行综述。结果:(1)NAC能减少COPD患者急性发作的发生率,改善临床症状,可能有助于肺功能的改善;(2)初步临床试验结果表明,长时间大剂量的NAC治疗有助于肺间质纤维化患者肺功能的改善;(3)NAC可以通过抗氧化作用,保护急性肺损伤及ARDS肺组织免受氧化作用损伤,从而减轻临床症状,改善氧合。结论:NAC是一种具有广泛前景的治疗急性和慢性呼吸道疾病的药物。     

P选择素在油酸诱导急性肺损伤大鼠肺组织中的表达及N-乙酰半胱氨酸对其影响的研究

目的探讨油酸(Olic Acid,OA)诱导的急性肺损伤(Acute Lung Injury,ALI)大鼠肺血管内皮P-选择素(P-selectin,Ps)表达的变化及N-乙酰半胱氨酸(N-acetylcysteine,NAC)的保护作用。方法成年雄性SD大鼠42只按随机化原则分为3组:油酸组(OA组n=18);对照组(n=6); N-乙酰半胱氨酸 油酸组(NAC组,n=18);按注射油酸后不同时间随机分为3组,1小时、3小时、6 小时组,行P选择素免疫组织化学染色及光密度测值,并检测肺组织匀浆髓过氧化物酶(MPO)、超氧化物岐化酶(SOD)、丙二醛(MDA)。结果Ps在OA诱导的ALI大鼠肺血管内皮1小时出现表达,3 小时表达达高峰,持续表达6小时(P<0．01);OA组各时点MPO、MDA升高,与对照组比较差异均有显著性(P<0．01),NAC组各时点MPO、MDA均低于相应时点OA组(P<0．01),但均高于对照组(P<0．01);OA组SOD明显降低,与对照组比较差异明显(P<0．01),NAC组各时点SOD均高于相应时点OA组(P<0．01),但均低于对照组(P<0．01);Ps表达与MPO、MDA成正相关(r=0．793, 0．886;P<0．01)。结论Ps在OA诱导的ALI大鼠肺血管内皮表达1小时升高,3小时表达达高峰, 持续表达6小时;NAC通过清除氧自由基抑制Ps在肺血管内皮的表达,对OA诱导ALI大鼠起保护作用。     

Prophylactic effect of N-acetylcysteine against sodium fluoride-induced blood oxidative stress in mice

Ninety female Balb/c mice were used. The animals were allocated to evenly six groups. While the first group was maintained as control, Groups 3, 4, 5, and 6 were administered 750 ppm, 1500 ppm, 3000 ppm, and 6000 ppm of N-acetylcysteine, respectively, for a period of 15 days. After day 15, Groups 2–6 were administered sodium fluoride, containing 100 ppm fluoride in drinking water, for another 15 days. Plasma malondialdehyde (MDA) levels and erythrocyte superoksid dismutase (SOD) and catalase (CAT) activities were determined at the beginning of the trial and on days 15 and 30. According to the data obtained in the present study, N-acetylcysteine, when administered at the indicated doses, did not produce a significant alteration in any of the three parameters investigated. On the other hand, while the plasma MDA level was determined to have increased significantly, erythrocyte SOD and CAT activities were ascertained to have decreased significantly in the group, which was administered sodium fluoride alone on day 30. In the groups, which were administered N-acetylcysteine prior to sodium fluoride, however, it was observed that, after sodium fluoride administration, plasma MDA levels and erythrocyte SOD and CAT activities drew closer to the values of the control group.     

人脐带间充质干细胞对急性肺损伤氧化应激的影响

目的探讨人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HUMSCs)对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)氧化应激失衡的作用。方法人脐带间充质干细胞的分离,培养和鉴定。将30只Wistar大鼠随机分为生理盐水(NS)对照组(A组)、LPS模型组(B组)和HUC-MSCs移植组(C组),每组10只。移植6h后,处死各组大鼠,取肺组织行病理学观察,肺湿/干重比测定,丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性检测。结果流式细胞术结果显示,纺锤样细胞高表达CD29、CD44和CD105,极低表达CD34,符合HUMSCs的特征。与A组比较,B组W/D和MDA含量明显升高(P<0.05),SOD活性明显降低(P<0.05)。与B组比较,C组W/D和MDA含量明显降低(P<0.05),SOD活性明显升高(P<0.05)。结论在大鼠模型中人脐带间充质干细胞移植能减轻肺损伤,并能降低肺组织MDA含量和提高SOD活性。     

葛根素对油酸致急性肺损伤大鼠的保护作用

目的探讨葛根素对油酸致急性肺损伤大鼠的保护作用。方法24只健康雄性SD大鼠,完全随机分为5组：正常对照组,油酸组和葛根素干预组,各8只。通过静脉注射油酸建立大鼠急性肺损伤模型。正常对照组：大鼠静脉注射0．9％氯化钠溶液0．1ml／kg;油酸组：大鼠静脉注射油酸0．1ml／kg;葛根素干预组：大鼠在注射油酸前30min腹腔注射葛根素30mg／kg。光镜下观察大鼠肺组织形态学改变;检测血清中肿瘤坏死因子α（TNF-α）含量,肺组织中超氧化物歧化酶（SOD）活性和丙二醛含量。结果肺组织形态学变化提示葛根素干预组大鼠肺组织炎症反应较油酸组减轻。油酸组和葛概素干预组均较正常对照组大鼠血清中TNF—α含量增加、肺组织中SOD活性降低、丙二醛含量增加[分别为（41．7±3．4）、（19．0±1．3）ng／L比（5．8±0．8）ng／L;（78±6）、（93±7）U／mg比（113±9）U／mg;（11．89±0．64）、（7．87±0．81）μmol／g比（2．49±0．28）μmol／g]（均P〈0．05）;但葛根素干预组上述3项指标均优于油酸组（均P〈0．05）。结论葛根素对油酸致急性肺损伤大鼠具有一定的保护作用,其机制可能与提高大鼠抗氧化能力、降低血清中TNF—α含量有关。     

N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5 mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50 mg/kg b.w.; p.o.) for 7 days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.     

N-acetylcysteine protects against fluoride-induced oxidative damage in primary rat hepatocytes

Fluoride induces the overproduction of free radicals, which might in turn affect various biochemical parameters. Therefore, the aim of this study was to elucidate the role of N-acetylcysteine (NAC) in decreasing fluoride-induced oxidative stress. The fluoride intoxicated (0.002; 0.082; 0.164 mmol/l) rat hepatocytes was pre-treated (60 min) and simultaneously treated with NAC (1 mmol/l). The resulting levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and intracellular reduced glutathione (GSH) were measured along with the total antioxidant status (TAS) to determine whether NAC treatment reduced cell damage and/or the antioxidant state. These results suggest that NAC pre-treatment provides protection against fluoride-induced oxidative stress in hepatocytes.     

谷氨酰胺对内毒素诱导大鼠肺组织氧化应激反应的影响

目的探讨谷氨酰胺对内毒素(LPS)诱导大鼠肺组织氧化应激反应的影响。方法雄性SD大鼠50只,随机分为5组(n=10):对照组(A组);LPS组(B组),股静脉注射LPS 5 mg/kg;C、D、E组为谷氨酰胺+LPS组,分别于LPS注入前1 h时,LPS注入同时,LPS注入后1 h时,均静脉注射谷氨酰胺0.75 g/kg。于注射LPS后4 h时处死大鼠,测定肺组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)、一氧化氮(NO)、总一氧化氮合酶(tNOS)水平,诱导型一氧化氮合酶(iNOS)活性及iNOS mRNA表达。结果与A组比较,B组肺组织SOD活性下降,MDA、NO、tNOS水平、iNOS活性及iNOS mRNA表达均升高(P<0.05及P<0.01);与B组比较,C、D组肺组织SOD活性升高,MDA、NO、tNOS水平、iNOS活性及iNOS mRNA表达降低(P<0.05及P<0.01),E组上述各项指标比较差异无统计学意义(P>0.05)。结论谷氨酰胺早期给药可减轻LPS诱导肺组织氧化应激反应。     

N-乙酰半胱氨酸对大鼠急性脊髓损伤后继发性脊髓损伤的保护作用

目的 探讨N-乙酰半胱氨酸(NAC)对大鼠脊髓急性损伤后继发性脊髓损伤的保护机制.方法 成年SD大鼠18只随机均分成单纯椎板切除(对照组)、急性脊髓损伤(损伤组)和急性脊髓损伤后NAC治疗(治疗组)三组.用30 g力量动脉瘤夹从两侧夹闭脊髓30 s建立脊髓损伤模型.治疗组术后15 min、1、2和3d分别予NAC 150 mg/kg腹腔注射;对照组和损伤组腹腔注射等量生理盐水.所有动物于术后3d处死取材,用凝胶电泳迁移率分析和免疫组化检测脊髓组织中核因子κB(NF-κB),ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)和IL-6表达.结果 损伤组脊髓组织中NF-κB、TNF-α、IL-1β和IL-6水平均比对照组升高(P＜0.05),治疗组脊髓组织中各因子水平均比损伤组显著降低(P＜0.05).结论 NAC可以通过抑制大鼠急性脊髓损伤后NF-κB的活性,进一步下调TNF-α、IL-1β和IL-6的表达,从而减轻继发性炎症反应所导致的脊髓损伤.     

氧化应激在利福平所致大鼠肝损伤适应性模型中的作用

目的 探讨利福平致大鼠肝损伤适应性现象及氧化应激可能涉及的参与过程。方法 将正常对照组和利福平实验组大鼠各16只分别予以生理盐水10 mL/（kg·d）和利福平混悬液100 mg/（kg·d）每日一次空腹灌胃,共持续7周,动态监测大鼠灌胃当天、第14天、第28天和第49天血清转氨酶、胆红素和碱性磷酸酶水平。于第14天处死两组各4只大鼠,第49天处死剩余大鼠,检测肝脏超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽-过氧化物酶（GSH-PX）活性,并观察其肝组织病理学改变。结果 与正常组相比,利福平实验组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TB）、直接胆红素（DB）水平在第14天达高峰,之后呈缓慢下降趋势（P<0.05）,至第49天时,与正常组相比差异无统计学意义（P>0.05）。相较正常组,利福平实验组大鼠MDA水平偏高,而SOD与GPX活性偏低（P<0.05）。大体标本可见利福平实验组大鼠肝脏黄染,光镜下可见肝组织存在脂肪变性、轻度坏死和炎症。结论 利福平可导致大鼠肝损伤适应性现象,且氧化应激在一定程度上参与了上述过程。     

氨溴索对高浓度氧和通气机联合所致大鼠急性肺损伤的防护作用

目的:研究氨溴索对高浓度氧和通气机联合所致大鼠急性肺损伤的防护作用。方法:将36只雄性SD大鼠随机分为3组。A组实施空气大潮气量通气,B组实施高氧大潮气量通气,C组为氨溴索干预组。测定左肺W/D值,BALF中性粒细胞计数、TNF-α、IL-1β、MIP-2含量以及肺组织MDA、SOD水平。结果:C组大鼠左肺W/D值、BALF中性粒细胞计数、TNF-α、IL-1β、MIP-2含量、肺组织MDA水平较B组显著下降,而SOD水平较B组显著增加。结论:氨溴索对高浓度氧和通气机联合所致大鼠急性肺损伤有较明显的防护作用。     

Effects of vitamin B-6 supplementation on oxidative stress and inflammatory response in neonatal rats receiving hyperoxia therapy

Hyperoxia is often used in the treatment of neonates. However, protracted use of hyperoxia leads to significant morbidity. The purpose of this study was to evaluate the effects of vitamin B-6 supplementation on oxidative stress and inflammatory responses in neonatal rats undergoing hyperoxia therapy. The study consisted of 2 parts: a survival study and a vitamin B-6 efficacy study for 16 days. Neonatal rats were randomly divided into either the control group, B-6 group (subcutaneously injected with 90 mg/kg/d of pyridoxal 5′-phosphate [PLP]), O₂ group (treated with 85% oxygen), or O₂ + B-6 group (simultaneously treated with 85% oxygen and 90 mg/kg/d PLP). After the survival study was done, the vitamin B-6 efficacy study was performed with duplicate neonatal rats sacrificed on the 3rd, 6th, 9th, and 16th day. Serum inflammatory cytokines, tissue pathology, and malondialdehyde (MDA) levels were measured. In the survival study, the survival rate of neonatal rats in the control, B-6, O₂, and O₂ + B-6 group on the 16th day were 100%, 100%, 25%, and 62.50%, respectively. The efficacy study showed lung polymorphonuclear granulocyte (PMN) and macrophage infiltration, increased liver hemopoiesis, and higher MDA levels in liver homogenates at days 3 through 16 in the O₂ group. Vitamin B-6 supplementation considerably increased serum inflammatory cytokines in either the 6th or 9th day and decreased liver MDA level before the 6th day. These results indicate that neonatal rats receiving hyperoxia treatment suffered divergent serum inflammatory responses and were in increased liver oxidative stress. Vitamin B-6 supplementation seemed to improve survival rates, change systemic inflammatory response, and decrease liver oxidative stress while neonatal rats were under hyperoxia treatment.