N-乙酰半胱氨酸通过AMPK/SIRT1途径抑制缺氧诱导的大鼠脑血管内皮细胞损伤

目的研究N-乙酰半胱氨酸(NAC)对缺氧诱导脑血管内皮细胞损伤的调节作用及分子机制。方法选择SD大鼠分离培养脑血管内皮细胞,分为常氧组、缺氧组、0. 5 NAC组(缺氧+0. 5 mol/L NAC)、1. 0 NAC组(缺氧+1. 0 mol/L NAC)、NAC+8-bAMP组(缺氧+1. 0 mol/L NAC+1. 0 mol/L 8-bAMP)。采用MTS法检测细胞增殖活力,采用TUNEL染色检测凋亡率,采用试剂盒检测氧化应激指标,采用Western blot检测凋亡基因、AMPK/SIRT1通路分子的表达量。结果缺氧组细胞OD490值、T-AOC含量及B淋巴细胞瘤2(Bcl-2)、p-AMP活化蛋白激酶(pAMPK)、去乙酰化酶Sirtuin1(SIRT1)表达量均明显低于常氧组;缺氧组细胞凋亡率、细胞中活性氧(ROS)、丙二醛(MDA)、8-羟基脱氧鸟苷(8-OHDG)含量及bcl-2相关X蛋白(bax)、细胞色素C(Cyt-C)、含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)的表达量均明显高于常氧组。0. 5 NAC组、1. 0 NAC组细胞OD490值、T-AOC量及Bcl-2、pAMPK、SIRT1表达量均明显高于缺氧组; 0. 5 NAC组、1. 0 NAC组细胞凋亡率、ROS、MDA、8-OHDG含量及Caspase-3、Cyt-C、Bax的表达量均明显低于缺氧组。NAC+8-bAMP组细胞OD490值、T-AOC及Bcl-2、p-AMPK、SIRT1表达量均明显低于1. 0 NAC组; NAC+8-bAMP组凋亡率、ROS、MDA、8-OHDG含量及Caspase-3、Cyt-C、Bax的表达量均明显高于1. 0 NAC组。结论 NAC能够通过激活AMPK/SIRT1通路来减轻氧化应激及线粒体凋亡介导的脑血管内皮细胞损伤。     

N-乙酰半胱氨酸对呼吸道病毒辅助治疗的研究进展和药学监护

目的:采用文献检索的方法对N-乙酰半胱氨酸辅助治疗呼吸道病毒的研究进行汇总分析,评价其有效性与安全性,对现阶段临床辅助治疗新型冠状病毒肺炎提供理论依据和临床证据。方法:以"乙酰半胱氨酸""N-acetylcysteine""流感病毒"为关键词,系统检索CNKI、万方、维普、SinoMed、Pubmed数据库,筛选文章,提取数据,进行分析。结果:共纳入16篇研究论文,包括动物试验、细胞试验以及案例报道,病毒涉及流感病毒、呼吸道合胞病毒以及腺病毒。N-乙酰半胱氨酸主要通过抑制NF-κB向细胞核的移位和MAPK p38的磷酸化两条途径发挥其抗氧化作用,进而抑制减轻肺组织炎症、肺水肿。结论:相关的细胞研究与动物研究证明N-乙酰半胱氨酸对呼吸道病毒有一定的抑制作用,能够减轻流感和流感样发作。并且由于其良好的祛痰作用,对于新冠肺炎患者症状可能有较好的改善作用。     

N-乙酰半胱氨酸对心肺转流下心脏直视手术患者肺功能的影响

目的观察N-乙酰半胱氨酸(N-acetylcysteine,NAC)对心肺转流(cardiopulmonary bypass,CPB)下心脏直视手术患者肺功能参数的影响。方法择期在CPB下行心脏瓣膜置换术的风湿性心脏病患者40例,性别不限,年龄40~65岁,体重45~80kg,ASAⅡ或Ⅲ级,心功能Ⅰ~Ⅲ级,随机均分为NAC组和对照组(C组)。NAC组:麻醉诱导后CPB前静脉输注NAC 100mg/kg,CPB开始后静脉持续输注NAC 40mg/kg至术毕。C组:等剂量用生理盐水作为安慰剂静脉输注。于麻醉诱导后(T0)、开胸后CPB前(T1)、术毕关胸后(T2)、术后5h(T3)、24h(T4)和48h(T5)检测呼吸指数(RI)、氧合指数(OI)、肺泡-动脉氧分压差(A-aDO2)和气道阻力(R)。结果与T0时比较,T2~T4时两组患者RI、A-aDO2明显升高(P0.05)、OI明显降低(P0.05)、T2和T3时两组患者气道阻力明显升高(P0.05)。与C组比较,T2~T4时NAC组RI和A-aDO2明显降低(P0.05)、OI明显升高(P0.05)、T2和T3时NAC组气道阻力明显降低(P0.05)。结论 N-乙酰半胱氨酸可以减轻CPB导致的肺功能损伤,对肺脏可能具有保护作用。     

N-乙酰半胱氨酸对脂多糖诱导的血管内皮细胞炎症损伤的影响

目的:探讨N-乙酰半胱氨酸(NAC)是否对脂多糖(LPS)刺激的血管内皮细胞具有保护作用,为NAC用于治疗种植体周围炎、牙周炎等提供理论基础。方法:通过细胞计数试剂盒(CCK-8)法检测不同浓度的LPS或NAC对人脐静脉血管内皮细胞(HUVECs)增殖的影响,以获得刺激HUVECs的最适药物浓度。添加最佳药物浓度的LPS和(或)NAC处理HUVECs 24 h,实时半定量聚合酶链反应(RT-qPCR)检测炎症因子白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)和细胞粘附分子-1(ICAM-1)的mRNA表达;酶联免疫吸附试验(ELISA)检测TNF-α和IL-8的蛋白表达;Western blot法检测ICAM-1和NF-κB信号通路的表达情况。结果:LPS刺激HUVECs过量表达炎症因子TNF-α、IL-8和ICAM-1。此外,LPS增加NF-κB通路的磷酸化P65(pP65)表达。然而,NAC预处理HUVECs后,显著抑制了LPS引起的TNF-α、IL-8和ICAM-1表达的增加及降低了pP65的分泌水平。结论:本结果表明NAC保护血管内皮细胞免受LPS介导的炎症损伤,从而减轻炎症反应,其潜在的机制可能与NF-κB信号通路有关。     

Involvement of Nrf2, JAK and COX pathways in acetaminophen-induced nephropathy: Role of some antioxidants

ObjectivesAcetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury.Design and methodRats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP.ResultsTreatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree.ConclusionThe combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.     

N-乙酰半胱氨酸对重症急性胰腺炎大鼠肠屏障保护作用机理的实验研究

目的观察N-乙酰半胱氨酸（NAC）对重症急性胰腺炎（SAP）大鼠肠屏障功能的保护作用及其可能机理。方法将80只Wistar大鼠随机（随机数字表法）分为正常对照组（CON组,n=8）、假手术组（SO组,n=24）、SAP组（n=24）及NAC组（n=24）,后3组再随机（随机数字表法）分为6、12及24 h 3个时间点组,每个时间点组8只大鼠。通过胰胆管逆行注射5%牛磺胆酸钠的方法制作大鼠SAP模型,SO组大鼠则通过胰胆管逆行注射生理盐水。NAC组大鼠于造模前1 h经腹腔注射NAC,而SO组和SAP组大鼠于相应时间点经腹腔注射生理盐水。CON组大鼠不做任何处理,麻醉后直接取右心室血5 mL及回肠组织约5 cm,余3组大鼠则于术后6、12及24 h麻醉后取材。检测血浆淀粉酶（AMY）、C-反应蛋白（CRP）、内毒素、D-乳酸及二胺氧化酶（DAO）含量;检测回肠组织总超氧化物歧化酶（T-SOD）、髓过氧化物酶（MPO）及丙二醛（MDA）含量;观察回肠上皮细胞的凋亡情况、回肠组织的病理学改变并对其进行评分;检测回肠组织bax和bcl-2 mRNA及其蛋白的表达水平。结果与同时相SAP组比较,NAC组大鼠各时相的血浆CRP水平均较低（P〈0.05）,而AMY水平在12 h和24 h时较低（P〈0.05）;NAC组大鼠的DAO、内毒素及D-乳酸水平在12 h和24 h时均较低（P〈0.05）,但DAO水平在6 h时高于SAP组（P〈0.05）;NAC组大鼠各时相回肠组织中的MPO及MDA水平均较低（P〈0.05）,而T-SOD水平则在12 h和24 h时较高（P〈0.05）;NAC组大鼠回肠上皮细胞的凋亡指数均较低（P〈0.01）,组织病理学评分在12 h及24 h时亦较低（P〈0.05）;NAC组大鼠回肠组织中bax mRNA及其蛋白的表达水平均较低（P〈0.05）,而bcl-2 mRNA及其蛋白的表达水平则均较高（P〈0.05）。结论 NAC对SAP大鼠的肠屏障功能具有保护作用,其机理除了抗氧化作用外,还可能与其抗凋亡作用有关。     

Propofol with N-Acetylcysteine Reduces Global Myocardial Ischemic Reperfusion Injury More than Ketamine in a Rat Model

Objective: We examined the cardioprotective effects of propofol and ketamine with and without N-acetylcysteine (NAC). Methods: 60 rats were divided into six groups of 10 rats each. Anesthesia induction was produced with an intraperitonal injection of ketamine in Groups 1–3 and propofol in Groups 4–6. NAC (200 mg kg^{? 1}) was given intraperitonally during anesthesia induction in Groups 3 and 6. Groups 2, 3, 5, and 6 were subjected to 90 s of myocardial ischemia by clamping the ascending aorta, and then reperfusion was begun by unclamping the ascending aorta. After 60 min of reperfusion, blood samples were taken from the ascending aorta for biochemical analyses, and heart tissue samples were taken for biochemical and histopathological analyses. Results: Creatine kinase (CK), myocardial band of creatine kinase (CK-MB), and troponin-I (Tn-I) levels were significantly higher in the ischemia–reperfusion groups (2, 3, 5, 6) compared to the nonischemic groups (1, 4). CK, CK-MB, and Tn-I levels did not differ significantly between the ketamine groups (1–3) and the propofol groups (4–6) p >. 05). Malondialdehyde levels were significantly higher in Groups 2 and 3 than in Group 1 and were significantly lower in Groups 4 and 6 than in Group 5 (p <. 05). Malondialdehyde levels in the propofol groups (4–6) were significantly lower than in the ketamine groups (1–3; p <. 05). Catalase levels in propofol groups were higher than ketamine groups. Superoxide dismutase levels were significantly higher in Group 6 than in Group 3 (p <. 05). Conclusions: In this rat model of global cardiac ischemia, propofol with NAC attenuates myocardial injury more than ketamine (with or without NAC).     

甲基苯丙胺与HIV-Tat蛋白协同改变大鼠血脑屏障通透性的氧化应激作用机制

目的 观察甲基苯丙胺与HIV-Tat蛋白协同对大鼠血脑屏障的作用机制.方法 雄性SD大鼠每天2次腹腔注射给予MA10 mg/kg的同时尾静脉注射给予HIV-Tat 400 ng/kg,连续7d,给药结束24 h后随机取10只大鼠尾静脉注射伊文思蓝检测脑组织EB含量,随机取5只大鼠断颈取脑,用于SOD活力、GSH和MDA含量的测定.余下2只大鼠快速断颈取脑,戊二醛-锇酸溶液固定前额叶皮质部分,透射电镜观察结构变化.结果 与正常对照组相比,实验组脑组织中EB含量不同程度增加,提示实验组血脑屏障通透性增加(P＜0.05);MDA含量升高、SOD活力和GSH含量不同程度降低,提示实验组氧化应激反应增强(P＜0.05).MA+Tat组与MA组、Tat组相比,EB含量升高明显,提示MA与HIV-Tat蛋白联用能协同增加血脑屏障通透性;MDA含量显著升高,SOD活力、GSH含量明显下降,提示MA与HIV-Tat蛋白联用能协同增强大鼠脑组织氧化应激反应(P＜0.01);NAC+MA+Tat组与MA+Tat组相比,EB含量降低,提示NAC能一定程度拮抗MA与HIV-Tat蛋白对血脑屏障通透性的影响(P＜0.01);MDA含量下降,SOD活力、GSH含量明显升高,反映NAC能在一定程度拮抗MA与HIV-Tat蛋白对大鼠脑内氧化应激反应增强作用(P＜0.01).各实验组在电镜下观察到血脑屏障一系列超微结构改变,如脑微血管内皮细胞肿胀变薄,血管周围胶质细胞和星形胶质细胞肿胀,胞饮小泡增加等,这些改变以MA+Tat组最为显著.结论 MA和HIV-Tat蛋白能改变血脑屏障通透性,两者具有协同作用,协同作用机制可能与氧化应激有关.     

N-乙酰半胱氨酸对游离脂肪酸诱导的胰岛素抵抗的影响

目的验证游离脂肪酸(FFA)诱导胰岛素抵抗,探讨抗氧化剂N-乙酰半胱氨酸(NAC)对FFA诱导的胰岛素抵抗的影响。方法2004年8月至2005年1月在中国医科大学附属盛京医院将24只正常Wistar大鼠随机分为4组,每组6只,分别静脉输注脂肪乳(IH)、NAC、IH NAC和生理盐水。清醒状态下行高胰岛素-正血糖钳夹,并测定血糖、FFA、胰岛素和丙二醛(MDA),计算胰岛素敏感指数(ISI)及葡萄糖输注率(GIR)。结果IH组FFA和MDA较其他3组显著增高,ISI及GIR显著降低。IH NAC组FFA和MDA显著降低,GIR显著增高。结论FFA浓度增高可诱导胰岛素抵抗,NAC可显著降低FFA和MDA浓度,改善胰岛素抵抗。