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-乙酰半胱氨酸对急慢性吸烟大鼠气道炎症的影响

目的 探讨抗氧化剂Ｎ－乙酰半胱氨酸（ＮＡＣ）对急慢性吸烟大鼠气道炎症的影响。方法 将Ｗｉｓｔａｒ大鼠随机分成：①吸烟组，②干预（吸烟＋ＮＡＣ）组，③对照组。其中吸烟组和干预组中动物均动态观察第１，２，７，１４，６０天的气道炎症反应，包括肺组织病理变化，肺泡灌洗液（ＢＡＬＦ）中细胞计数和分类，同时测定ＢＡＬＦ中ＩＬ－８含量。结果 急慢性吸烟大鼠的支气管周围和肺间质均有大量炎症细胞浸润，ＢＡＬＦ中白细     

Lipopolysaccharide treatment reduces rat platelet aggregation independent of intracellular reactive-oxygen species generation

High production of reactive-oxygen species (ROS) by blood cells is involved in damage of the vascular endothelium and multiple organ dysfunction in sepsis. However, little is known about the intraplatelet ROS production in sepsis and its consequences on platelet reactivity. In this study, we evaluated whether the treatment of rats with lipopolysaccharide (LPS) affects platelet aggregation through intraplatelet ROS generation. Rats were injected with LPS (1?mg/kg, i.p.), and at 2 to 72?h thereafter, adenosine diphosphate (ADP) (3–10?µM) induced platelet aggregation was evaluated. Production of ROS in platelets was measured by flow cytometry using 2′,7′-dichlorofluorescein diacetate (DCFH-DA). Treatment of rats with LPS time-dependently inhibited ADP-induced platelet aggregation within 72?h. The inhibitory effect of LPS on platelet aggregation was further increased when the platelets were incubated with polyethylene glycol-superoxide dismutase (PEG-SOD; 30?U/mL), polyethylene glycol-catalase (PEG-CAT; 1000?U/mL) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI; 10?µM). The ROS production in non-stimulated platelets did not differ between control and LPS-treated rats. However, in ADP-activated platelets, generation of ROS was increased by 3.0- and 7.0-fold, as evaluated at 8 and 48?h after LPS injection, respectively. This increased ROS production was significantly reduced when platelets were incubated in vitro with DPI, PEG-SOD or PEG-CAT. In contrast, treatment of rats with N-acetylcysteine (150?mg/kg, i.p.) significantly reduced the inhibitory effect of LPS on platelet aggregation, and prevented the increased ROS production by in vivo LPS. Our results indicate that the increased intraplatelet ROS production does not contribute to the inhibitory effect of LPS on platelet aggregation; however, the maintenance of redox balance in LPS-treated rats is fundamental to restore the normal platelet response in these animals.     

N-acetylcysteine attenuates renal alterations induced by senescence in the rat

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n = 6) or not (n = 6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.     

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。     

N-乙酰半胱氨酸对大鼠肺缺血再灌注损伤的保护作用

目的探讨N-乙酰半胱氨酸(NAC)对大鼠在体肺缺血再灌注(I/R)损伤的保护作用。方法建立大鼠在体肺缺血再灌注模型,将30只SD大鼠随机分成假手术对照组,缺血再灌注组(I/R组)和N-乙酰半胱氨酸组(NAC组),NAC组缺血前1 h给予腹腔注射N-乙酰半胱氨酸200 mg/kg。再灌注2 h后摘取左肺,分别对各组进行以下检测:肺湿/干比(W/D)、超氧化物歧化酶(SOD)活力、髓过氧化物酶(MPO)活性、丙二醛(MDA)含量并进行病理学检查及肺组织损伤定量评价(IQA)。结果I/R组肺W/D和IQA显著高于假手术组(P0.01),NAC组上述指标明显降低(P0.01)。病理学结果显示三组动物肺组织结构基本正常,假手术组无充血;与NAC组比较,I/R组肺组织充血明显、白细胞浸润更严重及肺间质高度淤血水肿。I/R组MDA含量和MPO活性较假手术组明显升高(P0.01),SOD活性显著下降(P0.01)。NAC能明显减少MDA含量和降低MPO活性,提高SOD活性(P0.01)。结论N-乙酰半胱氨酸对肺缺血再灌注损伤具有保护作用,可能与其抗氧化作用和抑制中性粒细胞激活有关。     

NAC对大鼠脑缺血再灌注引起胃黏膜损伤的影响

目的研究N-乙酰-L-半胱氨酸（N-acetylcysteine,NAC）对大鼠脑缺血再灌注引起应激性胃损伤的影响。方法采用四动脉结扎法建立大鼠全脑缺血模型,缺血后静脉注射NAC（150 mg/kg）,取胃后计数胃黏膜损伤指数（gastric mucosal damage index,GMDI）,测定胃黏膜组织中丙二醛（malonaldehyde,MDA）含量、超氧化物歧化酶（superoxide dismutase,SOD）活性,采用原位检测（TUNEL）法检测胃黏膜细胞凋亡情况。结果 NAC可以降低大鼠脑缺血再灌注引起应激性胃损伤时的胃黏膜损伤指数,使胃黏膜组织中MDA含量减少、SOD活性增强,抑制胃黏膜细胞凋亡。结论 NAC对大鼠脑缺血再灌注引起的应激性胃损伤具有保护作用,这种保护作用是通过抑制氧化应激、减少胃黏膜细胞凋亡而实现的。     

N-乙酰半胱氨酸联合维生素E对大鼠急性出血坏死性胰腺炎NF-κB的作用研究

目的 研究抗氧化剂N-乙酰半胱氨酸(NAC)联合维生素E(VitE)对大鼠急性胰腺炎动物模型胰腺组织NF-κB的作用,探讨两药的联合使用对急性胰腺炎的影响.方法 40只SD大鼠随机分为假手术(SO)组、出血坏死性胰腺炎(AHNP)组、NAC治疗组、NAC+ VitE治疗组,4组各10只.造模后12h取材,同时观察大鼠胰腺病理评分、血清淀粉酶(AMY)、丙二醛(MDA)、胰腺组织髓过氧化物酶(MPO)及胰腺组织中核因子-κB(NF-κB)的表达.结果 AHNP组胰腺病理评分、AMY、丙二醛、MPO及胰腺组织NF-κB的表达明显高于其他组(P＜0.01),NAC治疗组上述指标均低于AHNP组(P＜0.01),但仍高于SO组(P＜0.01),NAC+ VitE治疗组上述指标均低于AHNP组(P＜0.01)及NAC治疗组(P＜0.01),高于SO组(P＜0.01).结论 在AHNP时应用NAC+ VitE能明显减轻胰腺组织病理损伤,降低胰腺炎时血清AMY、丙二醛的浓度和胰腺组织MPO的活性,抑制胰腺组织中核因子-κB(NF-κB)的表达.     

Central antioxidant therapy inhibits parasympathetic baroreflex control in conscious rats

Baroreceptor reflex is an important system for neural control of blood pressure. Recently, reactive oxygen species (ROS) have been shown to play an important role in neuronal activity of central areas related to blood pressure control. The aim of this study was to investigate the effects elicited by ascorbic acid (AAC) and N-acetylcysteine (NAC) injections into the 4thV on the parasympathetic component of the baroreflex. Male Wistar rats were implanted with a stainless steel guide cannula into the 4thV. One day prior to the experiments, the femoral artery and vein were cannulated for pulsatile arterial pressure, mean arterial pressure and heart rate measurements and drug administration, respectively. After baseline recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 3 μg/kg, i.v.) and a depressor dose of sodium nitroprusside (SNP, 30 μg/kg, i.v.) before (control) and 5, 15, 30 and 60 min after AAC or NAC into the 4thV. Control PHE injection induced baroreflex-mediated bradycardia (-93 ± 13 bpm, n=7). Interestingly, after AAC injection into the 4thV, PHE injection produced a transient tachycardia at 5 (40 ± 23 bpm), 15 (26 ± 22 bpm) and 30 min (59 ± 21 bpm). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after AAC injection on 4thV (control: 151 ± 23bpm vs. 135 ± 18 bpm at 5 min after AAC, n=7). In the NAC treated group, PHE induced a reduction in reflex bradycardia at 5 min when compared to control (-11 ± 17 bpm vs. -83 ± 15 bpm, n=7). No changes were observed in baroreflex-mediated tachycardia evoked by SNP after NAC injection on 4thV. The antioxidants AAC and NAC may act in the central nervous system affecting the parasympathetic component of the cardiac baroreflex.     

N-乙酰半胱氨酸对重症急性胰腺炎大鼠肺损伤作用的实验研究

目的:探讨N-乙酰半胱氨酸(NAC)对重症急性胰腺炎(SAP)大鼠肺损伤的作用。方法:雄性SD大鼠30只,随机分为假手术组(SO组)、SAP组、NAC组。胆胰管逆行注射5%牛磺胆酸钠制备SAP模型,造模后30min腹腔注射5%NAC(0.2ml/100g)干预SAP模型,12h后处死大鼠。检测各组血清淀粉酶(AMY)、肺组织髓过氧化物酶(MPO)、胰腺和肺组织病理学评分、肺组织肿瘤坏死因子-α(TNF-α)和细胞间粘附分子-1(ICAM-1)mRNA表达的变化。结果:与SO组比较,SAP组AMY、MPO、胰腺和肺组织病理学评分明显升高(P<0.01),TNF-α和ICAM-1mRNA表达明显增强(P<0.01);应用NAC处理后,AMY和MPO水平下降,胰腺和肺组织损伤缓解,TNF-α和ICAM-1mRNA表达减弱,与SAP组有明显差异(P<0.01)。结论:NAC对SAP大鼠肺损伤具有保护作用,其机制可能与抑制肺组织TNF-α和ICAM-1mRNA的表达有关。