N-乙酰半胱氨酸防治内毒素所致肝损伤的实验研究

目的　探讨N 乙酰半胱氨酸 (NAC)可否对内毒素性肝损伤进行抑制及相应的细胞、分子机制。方法　健康雄性昆明种小鼠 30只随机分为肝损伤组、NAC组和对照组 ,不同给药后检测肝匀浆肿瘤坏死因子(TNF) α、丙二醛 (MDA)和还原型谷胱甘肽 (GSH)含量变化 ,并行聚丙烯酰胺凝胶电泳 ,分析NAC对核因子(NF) κBp6 5、IκBα的影响。 结果　NAC不但使肝组织TNF α、MDA含量降低 ,GSH含量升高 ,且抑制了内毒素诱导胞质IκBα降解和NF κBp6 5的表达。 结论　NAC可能通过调整库普弗细胞氧化还原平衡 ,影响NF κBp6 5活化 (核易位 ) ,从而抑制了TNF α等炎性因子基因的表达 ,减轻肝损伤。     

乙酰半胱氨酸对老年慢性阻塞性肺疾病患者炎性反应和氧化应激的影响

目的 探讨乙酰半胱氨酸对老年慢性阻塞性肺疾病(COPD)患者炎性反应和氧化应激的影响.方法 将60例COPD患者按机械抽样法随机分为治疗组和对照组,每组30例,对照组予以常规治疗,治疗组在此基础上加用乙酰半胱氨酸泡腾片治疗,疗程8周.两组患者在治疗前后均行血清肿瘤坏死因子α (TNF-α)、白细胞介素6(IL-6)、白细胞介素8(Ⅱ-8)、超氧化物歧化酶(SOD)和丙二醛(MDA)的检测.结果 治疗组治疗前后血清SOD、MDA分别为(51.08±7.80)、(75.09±8.03)μU/L和(7.13±0.89)、(4.51±0.61)μmol/L,对照组分别为(52.12±7.31)、(65.16±8.01)μU/L和(7.11±0.87)、(6.21±0.78)μmol/L,两组治疗后均较治疗前明显改善(P＜ 0.01或＜0.05),且两组治疗后比较差异亦有统计学意义(P＜0.05).治疗组治疗后血清IL- 6、IL-8、TNF-α均较治疗前下降[分别为( 18.25±7.24)ng/L比(29.02±6.70) ng/L、( 115.28±13.76) ng/L比(148.99±16.61)ng/L、(20.43±3.92) ng/L 比(32.32±8.18)ng/L](P＜0.05),对照组无明显改变[(25.25±7.55) ng/L比(28.82±7.54) ng/L、( 136.27±12.97) ng/L比(150.21±17.52) ng/L、(28.43±3.92) ng/L比(32.56±8.78) ng/L](P＞ 0.05);两组治疗后比较差异有统计学意义(P＜0.05).结论 乙酰半胱氨酸可改善COPD患者氧化/抗氧化失衡和减轻炎性反应,为COPD的治疗发挥作用.     

The Distribution Kinetics of Topical 14C‐Sulfur Mustard in Rabbit Ocular Tissues and the Effect of Acetylcysteine

Sulfur mustard (2,2‐dichlorodiethyl sulfide; HD), is a potent alkylating agent which in liquid or vapor form is capable of causing severe injuries to skin and respiratory tract, and was shown to cause short‐ and long‐term ocular injuries. N‐Acetylcysteine (NAC) may act as a mucolytic agent, changing the “wetting” and scavenging properties of the cornea and thus the adhesion of HD. Moreover, NAC is a scavenger of HD, an antioxidant and a glutathione precursor, which was shown to reduce HD toxicity in various systems. The ocular distribution of ¹⁴C, after topical application of liquid ¹⁴C‐sulfur mustard (¹⁴C‐HD) to the rabbit cornea, and the role of NAC in reducing HD retention and toxicity are presented in this study. Groups of rabbits were exposed to 0.4 µL of liquid ¹⁴C‐HD, placed at the center of the cornea, with or without NAC treatment. Fifty µL NAC (10% aqueous solution) was topically applied, 10 minutes before and 10 minutes after HD exposure. Three time points were evaluated: 1, 6, and 24 hr after HD exposure, six rabbits per time point. Evaluation consisted of clinical observation, measurement of biochemical parameters in aqueous humor (AQ), counting radioactivity concentration in ocular tissues, and histology of corneal sections. One hour after corneal exposure to liquid ¹⁴C‐HD, approximately 2% of total applied radioactivity was recovered. The highest ¹⁴C concentration was found in the cornea, followed by the tarsal section of eyelid, aqueous humor, nictitating membrane, and the frontal sclera (including conjunctiva). The rate of radioactivity decrease varied from one ocular tissue to the other, the highest rate was found in aqueous and vitreous humors, also in accordance with their higher turnover rates. The NAC treatment reduced the radioactivity in most ocular tissues. The HD exposure caused typical clinical and histological signs of HD intoxication, and increased the aqueous protein and prostaglandin (PGE) content. The NAC treatment lowered eyelid edema but had no effect on AQ protein or PGE content; however, there was some aggravating effect of the NAC treatment on corneal epithelial cells, seen at 1 and 6 hr after exposure.     

N-乙酰半胱氨酸防治放射性肺损伤疗效观察

目的：观察胸部肿瘤放射治疗期间应用N-乙酰半胱氨酸（NAC）对放射性肺损伤的保护作用。方法86例胸部肿瘤患者接受常规放射放疗,随机分成两组,设放疗＋N-乙酰半胱氨酸组（RT＋N）和单纯放疗组（ RT）,两组通过胸部CT进行放疗后观察,严重程度按RTOG放射性肺炎分级标准进行观察,放疗前和放疗4周后每2周观测血浆转化生长因子（TGF-β1）,白介素1（IL-1）、白介素4（IL-4）、肿瘤坏死因子（TNF）指标,在放疗8周结束后终止观察。结果86例患者放疗3个月,RT＋N组放射性肺炎≥2级者占23．3％而RT组≥2级者占53．5％。 RT＋N组放射性肺炎发生率低于RT组,两组差异有统计学意义（P＜0．01）;6、9、12个月时,肺纤维化的发生率（RT＋N）组为28．4％、25．4％、22．4％;RT组分别为58．4％、54.4％、52．4％,两组比较差异有统计学意义（ P＜0．05）。 TGF-β1、IL-1、IL-4、TNF水平,在放疗期间及8周后,RT组明显高于RT＋N组。结论 N-乙酰半胱氨酸在胸部肿瘤患者放射治疗时能够减少急慢性放射性肺损伤的发生率,同时也能降低TGF-β1、IL-1、IL-4、TNF的含量与表达。     

乙酰半胱氨酸镁盐治疗大鼠肝纤维化的实验研究

N-乙酰半胱氨酸(NAC)作为GSH的前体物,有强大的抗氧化能力.镁为缺电子原子,易与NAC形成稳定的盐,参与控制细胞的完整性和细胞的免疫功能稳定,因此镁原子有益作用不仅能改善NAC的给药屏障,并有助于NAC发挥更强的抗肝纤维化作用[1-2].     

基于乙酰半胱氨酸泡腾片对间质性肺疾病疗效观察

目的 总结分析乙酰半胱氨酸泡腾片治疗间质性肺疾病的临床疗效。方法 选取64例间质性肺疾病（ILD）患者作为研究对象,将其随机均分为2组（n=32）,对照组给予常规泼尼松治疗,观察组患者在常规治疗基础上,给予口服乙酰半胱氨酸泡腾片治疗。观察2组患者的临床症状缓解情况、肺功能变化、肺部病灶面积改变以及不良反应发生情况,对比2组的差异。结果 治疗后,2组患者的临床症状、肺功能改变情况以及肺部病灶变化均有所改善,对照组无效8例（25.00%）,有效24例（75.00%）,观察组无效3例（9.38%）,有效29例（90.63%）,观察组治疗效果显著优于对照组（P〈0.05）;观察组4例患者出现不良反应,对照组11例患者出现不良反应。结论 采用乙酰半胱氨酸泡腾片治疗间质性肺疾病疗效明显,使用方便,安全性高,是治疗间质性肺疾病的有效药物,值得临床推广使用。     

乙酰半胱氨酸对稳定期慢性阻塞性肺疾病患者急性加重率及生活质量的影响研究

目的观察乙酰半胱氨酸对稳定期慢性阻塞性肺疾病(COPD)患者急性加重率及生活质量的影响。方法选择2012年4月—2013年8月在鄂尔多斯市中心医院门诊就诊的稳定期COPD患者86例,随机分为治疗组43例和对照组43例。对照组给予常规治疗,治疗组在常规治疗的基础上加用乙酰半胱氨酸。观察两组患者肺功能指标、急性加重情况,并采用中文版COPD评估测试(CAT)问卷评价其生活质量。结果两组患者治疗前及治疗后6、12个月第一秒用力呼气容积(FEV1)、FEV1占预计值百分比(FEV1%)、FEV1/用力肺活量(FVC)比较,差异均无统计学意义(P0.05)。治疗前,两组患者中文版CAT问卷总分比较,差异无统计学意义(P0.05);治疗后6、12个月,治疗组患者中文版CAT问卷总分低于对照组,差异均有统计学意义(P0.05)。治疗前及治疗6个月后,两组患者急性加重率比较,差异均无统计学意义(P0.05);治疗12个月后,治疗组急性加重率低于对照组,差异有统计学意义(P0.05)。结论长期口服乙酰半胱氨酸可减少COPD患者急性加重率,改善其生活质量。     

乙酰半胱氨酸溶液联合特布他林治疗慢性阻塞性肺疾病急性加重期的临床研究

目的 探讨乙酰半胱氨酸溶液联合特布他林治疗慢性阻塞性肺疾病急性加重期（AECOPD）的临床效果。方法 选取2018年2月—2020年2月天津市第五中心医院（北京大学滨海医院）急诊留观病房收治的106例AECOPD患者,根据随机数字表法将其分为对照组（n=53）和治疗组（n=53）。对照组给予硫酸特布他林气雾剂吸入治疗,0.5 mg/次,3次/d。治疗组在对照组基础上给予吸入用乙酰半胱氨酸溶液雾化吸入,3 mL/次,2次/d。所有患者均连续治疗14 d。观察两组临床疗效及典型表现的缓解时间,比较治疗前后两组咳嗽和咳痰的评估问卷（CASA-Q）总分、慢性阻塞性肺疾病患者自我评估测试（CAT）问卷评分、第1秒用力呼气容积（FEV₁）与用力肺活量比值（FEV₁/FVC）、FEV₁占预计值、最大自主通气量（MVV）、深吸气量（IC）及血清和肽素（copeptin）、总抗氧化能力（TAC）、谷胱甘肽过氧化物酶（GSH-Px）、8-羟基脱氧鸟苷（8-OHdG）、内皮素-1（ET-1）水平。结果 治疗后,治疗组患者总有效率是94.3%,较对照组81.1%显著提高（P<0.05）。治疗组各项典型表现（喘息、咳痰、咳嗽、肺部哮鸣音）的缓解时间均显著短于对照组（P<0.05）。治疗后,两组CASA-Q总分均显著增加,CAT问卷评分则显著降低（P<0.05）;且治疗后,治疗组CASA-Q总分、CAT问卷评分改善优于对照组（P<0.05）。治疗后,两组FEV₁/FVC、FEV₁占预计值、MVV、IC值均较本组治疗前显著提高（P<0.05）;且治疗后,治疗组肺功能参数值的提高作用较同期对照组更显著（P<0.05）。治疗后,两组血清copeptin、8-OHdG及ET-1水平均较本组治疗前显著下降,但血清TAC、GSH-Px水平则均显著上升（P<0.05）;治疗后,治疗组血清学指标改善优于对照组（P<0.05）。结论 乙酰半胱氨酸溶液联合特布他林治疗AECOPD总体疗效确切,能安全有效且迅速地缓解患者呼吸道症状,改善患者肺功能及生活质量,可能与机体炎症及氧化应激反应的显著减轻有关。     

Hemolysis and Hemolytic Uremic Syndrome following Five-fold N-Acetylcysteine Overdose

Context. Intravenous acetylcysteine (Acetadote? in the US) is the treatment of choice for acute acetaminophen poisoning in most of the world. However, the complicated dosing regimen is prone to errors in preparation and administration. Case report. A 21 year-old woman (70 kg) took an overdose of acetaminophen and ethanol. Her serum acetaminophen concentration was > 200 mg/L. Acetylcysteine infusion was ordered. Due to misreading of the columns in the table in the Acetadote? package insert, she received a five-fold overdose of 52.5 g of acetylcysteine in 500 mL over 1 h and then 17.5 g of acetylcysteine in 500 mL to run over 4 h. The dose error was detected 20 min into the second infusion. Her acetaminophen concentration fell quickly, and her highest transaminase concentrations occurred day 2. Her hemoglobin and hematocrit quickly dropped from 14.8 g/dL and 44.0% on admission to 6.2 g/dL and 17.3% on day 7. Subsequently she developed hematuria and a rapidly rising serum creatinine. She was transferred to a tertiary care hospital, where she underwent hemodialysis every two days for two weeks, transfusions of packed red blood cells, and plasmapheresis until hematologic testing ruled out thrombotic thrombocytopenia purpura. Discussion. A five-fold overdose of acetylcysteine was followed by unexpected hemolysis and acute renal failure. The mechanism of hemolysis after acetylcysteine overdose is unclear. A simpler infusion regimen with standard concentrations would prevent a similar error.