乙酰肝素酶在肺癌侵袭转移及治疗中作用的研究进展

乙酰肝素酶是一种β-D-葡萄糖醛酸内切酶,为体内惟一能够降解硫酸乙酰肝素蛋白多糖的酶,可以在特定部位裂解硫酸乙酰肝素蛋白多糖,破坏细胞外基质及基底膜,并参与恶性肿瘤新生血管的形成,与恶性肿瘤的侵袭转移密切相关,乙酰肝素酶由此成为抗肿瘤作用的新靶点,其抑制剂有望成为临床抗肿瘤治疗的新途径.本文就乙酰肝素酶在肺癌侵袭转移及治疗中作用的研究作一综述.     

乙酰谷酰胺抗疲劳作用的研究

目的 探讨乙酰谷酰胺抗疲劳作用.方法 对小鼠灌胃乙酰谷酰胺200 mg/(kg·d),以负重游泳为运动模型,测定力竭游泳时间、血红蛋白(HB)、定量负荷后血乳酸和血尿素氮(BUN)及缺氧耐受时间.结果 乙酰谷酰胺能够增加机体HB的含量,延长小鼠力竭游泳时间和耐缺氧时间,降低定量负荷后血乳酸和BUN水平.结论 乙酰谷酰胺具有消除疲劳,提高运动能力的作用.     

乙酰硫酸肝素在造血系统及免疫系统中的作用

乙酰硫酸肝素是一种线性多糖,广泛存在于细胞表面和细胞外基质中,并在此与生长因子、生长因子结合蛋白、细胞外蛋白酶、蛋白酶抑制剂、化学物质和黏附蛋白相互作用.乙酰硫酸肝素在造血系统及免疫系统中的重要作用已引起了学者们的广泛重视,对乙酰硫酸肝素合成调控和功能研究有了很大进展.现将近年来对乙酰硫酸肝素在造血调控以及免疫学方面作用的研究进展综述如下.     

乙酰肝素酶与动脉粥样硬化

动脉粥样硬化是致死率较高的常见心血管疾病,乙酰肝素酶是能够裂解细胞外膜中硫酸乙酰蛋白多糖上侧链乙酰肝素的一种内切性β-D-葡萄糖醛酸糖苷酶,且其非酶活性也在许多正常生理活动或病理疾病中发挥作用.研究表明乙酰肝素酶与动脉粥样硬化的形成和进展有着紧密的联系.本文综述了乙酰肝素酶损伤内皮、促凝、诱导炎症因子及脂质聚集等作用,...     

蝇蛆壳聚糖对高脂血症大鼠的降脂保肝作用

目的 研究不同脱乙酰度的蝇蛆壳聚糖对实验性高脂血症大鼠的降脂保肝作用.方法　采用酸碱化学法制备不同脱乙酰度的蝇蛆壳聚糖,并用红外扫描鉴定其结构.取大鼠给高脂饲料造模的同时连续分别给予不同脱乙酰度的蝇蛆壳聚糖8 w,测定大鼠血清胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,测定肝脏指数和肝组织中TC含量,并对各组大鼠肝脏进行病理观察.结果 各脱乙酰度组蝇蛆壳聚糖均能显著降低血清TC、TG、LDL-C含量(P<0.01),显著升高HDL-C含量(P<0.01),降低大鼠的肝脏系数及肝组织TC含量(P<0.01),并能减轻肝细胞脂变程度.结论 不同脱乙酰度的蝇蛆壳聚糖能调节实验性高脂血症大鼠血脂代谢,抑制肝脏脂肪沉积,有良好的降脂保肝作用,其作用与脱乙酰程度呈正相关.     

乙酰紫草素对HCV复制的影响及其作用机制研究

目的探讨乙酰紫草素对HCV复制的影响及其作用机制。方法 (1)体外培养Huh7细胞,用不同浓度乙酰紫草素溶液与Huh7细胞进行共同培养,采用MTS法检测细胞的相对活力,观察乙酰紫草素对Huh7细胞的毒性作用。(2)采用JFH-1毒株感染Huh7细胞后,用不同浓度(0、0. 1、0. 2、0. 4、0. 8μM)的乙酰紫草素溶液进行处理,检测HCV RNA以及HCV core蛋白的表达水平,观察乙酰紫草素对Huh7细胞中HCV JFH-1复制的影响。(3)取JFH-1感染的Huh7细胞分为HCV组和HCV+乙酰紫草素组,HCV+乙酰紫草素组用0. 8μM乙酰紫草素处理,HCV组不处理;取未感染JFH-1的Huh7细胞,分为乙酰紫草素组和对照组,乙酰紫草素组用0. 8μM乙酰紫草素处理,对照组不处理。通过检测LC3 mRNA以及LC3B蛋白的表达水平,观察乙酰紫草素对细胞自噬标志因子LC3表达的影响。结果 (1)乙酰紫草素浓度在1. 0μM或更低时对Huh7细胞生长影响很小或没有影响,在2. 50μM以上时表现出明显的细胞毒性作用。(2)不同浓度乙酰紫草素(0. 1、0. 2、0. 4、0. 8μM)处理组细胞内HCV RNA水平均显著低于未用乙酰紫草素处理组,差异有统计学意义(P 0. 05),HCV core蛋白的表达量均显著低于未用乙酰紫草素处理组。(3)在基因水平上,LC3 mRNA的表达水平表现为HCV组对照组 HCV+乙酰紫草素组乙酰紫草素组,差异有统计学意义(P 0. 05);在蛋白水平上,LC3B蛋白的表达水平表现为HCV组对照组 HCV+乙酰紫草素组乙酰紫草素组。结论乙酰紫草素可以抑制HCV复制,同时下调自噬标志因子LC3的表达,可通过调节细胞自噬途径影响HCV病毒的复制。     

人肝脏内乙酰水扬酸酯酶活性的增龄变化

酯酶在药物代谢过程中起重要作用。通过生物转化,酯酶不仅能使许多药物失活,而且还使无活性药物转化成活性形式。酯酶中以乙酰水扬酸酯酶尤为重要,乙酰水扬酸类药物的药理效应取决于血浆中乙酰水扬酸酯酶的浓度大小。实验报告年龄对血浆中的乙酰水扬酸酯酶的活性没有影响,机体衰弱与乙酰水扬酸水解过程障碍有关,这是由于酶的含量减少并不是酶的活性改变。     

用乙酰半胱氨酸预防中度肾功能不全患者行选择性冠脉血管造影术后的肾功能急剧恶化

抗氧化剂乙酰半胱氨酸可用于预防有肾功能损害的患者行计算机体层摄影(CT)扫描时的急性造影剂肾毒性,然而,将它用于冠脉血管造影术的作用仍未明了。作者研究评估有中度肾功能不全的患者行选择性冠脉血管造影术时口服乙酰半胱氨酸预防肾功能急剧恶化的作用。     

N-乙酰半胱氨酸对自发性高血压大鼠血压及相关因素的影响

目的探讨应用NAC治疗对高血压的影响。方法雄性自发性高血压大鼠(n=30),随机分成N-乙酰半胱氨酸组、安慰剂组和基础组三组,基础组入选后即处死留取血标本检测。N-乙酰半胱氨酸组和安慰剂组测量实验前后收缩压,并检测大鼠血清NO含量及白细胞介素1含量。结果实验结束时N-乙酰半胱氨酸组血压明显低于安慰剂组(P<0.05)。N-乙酰半胱氨酸组血浆NO浓度明显高于安慰剂组(P<0.05)。N-乙酰半胱氨酸组白细胞介素1含量低于安慰剂组(P<0.05)。结论大鼠饮用含N-乙酰半胱氨酸(10g/L)自来水能降低血压,提高血浆NO和降低白细胞介素1含量,对大鼠心血管系统有保护作用。     

海舒必与乙酰谷酰胺存在配伍禁忌

海舒必（注射用头孢哌酮钠舒巴坦钠）主要成分为孢哌酮钠及舒巴坦钠，可抑制细菌细胞壁的合成，从而达到其杀菌的作用。乙酰谷酰胺为谷胺酰胺的乙酰化合物，有改善神经细胞代谢。维持神经应激能力及降低血氨，改善脑功能的作用.2005年7月第1版“318种静脉注射药物的药理表”中，头孢哌酮钠舒巴坦钠与乙酰谷酰胺之间无配伍禁忌。     

Inhibition of development of tolerance to nitroglycerin by preventive administration of N-acetylcysteine in rats

The efficacy of N-acetylcysteine in reversing nitrate tolerance has been controversial. This study examined whether continuous administration of N-acetylcysteine, a sulfhydryl compound, can prevent the development of tolerance to nitroglycerin; its acute effects on developed tolerance were also assessed. Rats were treated with subcutaneous injections of 1) 100 mg/kg nitroglycerin, 2) 100 mg/kg nitroglycerin and 700 mg/kg N-acetylcysteine, 3 times a day for 3 days. The sensitivity to nitroglycerin was studied in aortic preparations. The degree of developed tolerance to nitroglycerin was partially inhibited by simultaneous injection of N-acetylcysteine. Subsequent in vitro preincubation of aortic strips with nitroglycerin (10(-5) M) reduced the subsequent nitroglycerin sensitivity of vessels from rats treated with nitroglycerin and N-acetylcysteine; sensitivity returned to the initial control level after in vitro preincubation with N-acetylcysteine. The nitroglycerin sensitivity of vessels from rats treated only with nitroglycerin, though, was not affected by in vitro preincubation with N-acetylcysteine. In conclusion, N-acetylcysteine is not effective in reversing the high degree of tolerance developed to nitroglycerin. However, continuous administration of N-acetylcysteine is effective in preventing the development of nitroglycerin tolerance.     

Effects of N-acetylcysteine on oxidant-antioxidant balance in oleic acid-induced lung injury

The antioxidant and anti-inflammatory properties of N-acetylcysteine has been documented in many experimental lung injury models. Because intravenous injection of oleic acid induces histopathologic changes similar to those seen in human acute lung injury or acute respiratory distress syndrome, the authors evaluated the effects of N-acetylcysteine (NAC) on oxidative stress and lung damage in an oleic acid (OA)-induced lung injury model. Thirty-five rats were divided into 5 groups as sham, NAC, OA, pre-OA-NAC, and post-OA-NAC. Lung damage was induced by intravenous administration of oleic acid. Pre-OA-NACgroup received intravenous (IV) N-acetylcysteine 15 minutes before oleic acid infusion and post-OA-NAC group received IV N-acetylcysteine 2 hours after oleic acid infusion. In both of the N-acetylcysteine treatment groups, blood and tissue samples were collected 4 hours after oleic acid infusion, independent from the time of N-acetylcysteine infusion. In other groups, blood and tissue samples were collected 4 hours after ethanol, NAC, or OA infusions. Serum myeloperoxidase activity, total antioxidant capacity, malondialdehyde levels, and lung tissue Na+ - K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The administration of N-acetylcysteine significantly restored Na+ - K+ ATPase activity and total antioxidant capacity levels and ameliorated lung architecture. N-acetylcysteine has been shown to have some attenuating effects in experimental animal studies. However, further investigations are necessary to suggest N-acetylcysteine as a treatment agent in critically ill patients with lung injury.     

Nitrate tolerance in epicardial arteries or in the venous system is not reversed by N-acetylcysteine in vivo, but tolerance-independent interactions exist

N-acetylcysteine is assumed to reverse nitrate tolerance by replenishing depleted intracellular sulfhydryl groups, but data on interactions of N-acetylcysteine and nitrates in patients with stable angina are controversial and disappointing. Therefore, we studied the effect of N-acetylcysteine on nitrate responsiveness of epicardial arteries and of the venous system (assessed as changes in effective vascular compliance) in dogs (n = 12) during long-term nitroglycerin treatment (1.5 micrograms/kg/min i.v. for 5-6 days). In dogs with nitroglycerin-specific tolerance (shift of venous or epicardial artery dilation to 15-17-fold higher dosages), N-acetylcysteine (100 mg/kg i.v.) had no dilator effect and did not alter the dose-response relations of nitroglycerin. Yet, in nontolerant dogs (n = 17), N-acetylcysteine augmented (1.5-2.0-fold) the dilation of epicardial arteries and the reduction of peripheral vascular resistance induced by 0.5-1.5 micrograms/kg/min nitroglycerin. In vitro, the augmentation of purified guanylate cyclase activity by nitroglycerin (10-100 microM) was potentiated by N-acetylcysteine (0.01-1.0 mM) in saline or in canine plasma, but N-acetylcysteine alone was ineffective. We conclude that 1) N-acetylcysteine does not restore nitroglycerin responsiveness in tolerant epicardial arteries or veins in vivo, 2) a small, tolerance-independent augmentation of nitroglycerin-induced dilation may result from N-acetylcysteine-induced extracellular formation of a stimulant of guanylate cyclase from nitroglycerin.     

Portal and systemic haemodynamic action of N-acetylcysteine in patients with stable cirrhosis.

The effects of intravenous N-acetylcysteine on hepatic and systemic haemodynamics were investigated in 11 patients with stable cirrhosis (eight alcohol; two primary biliary cirrhosis; one cryptogenic). N-acetylcysteine administration had no effect on the mean heart rate or mean arterial blood pressure despite a significant fall in systemic and pulmonary vascular resistance. Cardiac index increased but estimated liver blood flow and portal venous pressure did not change significantly. Administration of N-acetylcysteine resulted in increased oxygen delivery to the tissues because of the increased cardiac index but this was not accompanied by a rise in either arteriovenous oxygen extraction ratio or mean tissue oxygen consumption. Therefore N-acetylcysteine administration seems to confer no haemodynamic benefit to patients with cirrhosis.     

Topical N-acetylcysteine for lamellar ichthyosis

The antioxidant N-acetylcysteine has an antiproliferative effect on a culture of human keratinocytes. We report a patient with lamellar ichthyosis satisfactorily treated with topical N-acetylcysteine.     

N-acetylcysteine infusion in viral myocarditis:: A case report

N-acetylcysteine improves survival in established acute liver failure following paracetamol overdose by reducing the incidence of multiorgan failure. These benefits are thought to be related to decreased tissue hypoxia by the enhancement of both oxygen delivery and oxygen extraction. Similar findings have been recorded in critically ill patients from an alternative aetiology. The cardiovascular properties of N-acetylcysteine are to increase stroke volume index, and thus cardiac output, although there is no effect on cardiac output in normal subjects. N-acetylcysteine is known to improve myocardial contraction in a hamster model of chronic myocardial ischaemia, but such effects have not previously been described in humans. We report the beneficial circulatory effect of N-acetylcysteine in a patient with marked left ventricular dysfunction secondary to acute viral myocarditis.     

N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis.

N-isobutyrylcysteine (NIC), a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine (NAC), was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound. Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second (FEV1) >40% and reversibility < or = 10% predicted were treated with oral NIC 300 mg b.i.d. or placebo for 24 weeks. Steroids, NAC, antibiotics, and nonsteroid anti-inflammatory drugs use were restricted. Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis. Spirometry was performed at each visit. Six hundred and thirty-seven patients were randomized to treatment with NIC (n=316) or placebo (n=321). NIC did not prolong the time to first exacerbation (life-table analysis, p=0.59) and no increase in FEV1 or forced vital capacity was observed. Altered taste perception, taste loss and anosmia occurred more often in the NIC group (p<0.001). In conclusion, N-isobutyrylcysteine, a N-acetylcysteine-like drug with a greater bioavailability has, contrary to N-acetylcysteine, no effect on exacerbations in chronic bronchitis. This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels (other than glutathione) produced by N-acetylcysteine therapy.     

N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease

Oxidative stress may play a role in chronic obstructive pulmonary disease (COPD) exacerbations. There is heterogeneity in the literature with regard to the impact of antioxidant therapy on COPD exacerbation frequency. Clinical trials of N-acetylcysteine in COPD were identified in unrestricted searches of MEDLINE, CINAHL, International Pharmaceutical Abstracts and the Cochrane Register. Randomized, controlled trials which reported exacerbations over a treatment period > or =3 months were selected. Two observers independently extracted data regarding exacerbation number over the treatment period in subjects allocated to either N-acetylcysteine or placebo. Data were analyzed using inverse-variance weighted random effects meta-analysis methodology. Meta-analysis of data from 8 trials (randomized n = 2,214) indicated that N-acetylcysteine significantly reduced the odds of experiencing one or more exacerbations over the treatment period (odds ratio = 0.49, 95% confidence interval [0.32-0.74], p = 0.001). Treatment effect was not reduced in studies which enrolled >50% active smokers (odds ratio = 0.36 [0.24-0.55], p < 0.001), although a greater effect was observed with exclusion of subjects using concurrent inhaled corticosteroids (odds ratio = 0.42 [0.32-0.54], p < 0.0001), suggesting that inhaled steroids attenuate the effect of N-acetylcysteine. The use of N-acetylcysteine significantly reduces the odds of exacerbation in patients with COPD, an effect possibly attenuated by inhaled steroids but not smoking. This analysis suggests treatment with N-acetylcysteine may be beneficial in a subset of patients with COPD.     

N-acetylcysteine for the prevention of contrast-induced nephropathy

OBJECTIVE: Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients. Although patients are often given N-acetylcysteine to prevent renal injury from contrast agents, there are no clear guidelines supporting its use. We conducted a systematic review to determine whether administering N-acetylcysteine around the time of contrast administration reduces the risk of contrast-induced nephropathy. DESIGN: We searched MEDLINE, EMBASE, the Cochrane Collaboration Database, bibliographies of retrieved articles, and abstracts of conference proceedings, and consulted with experts to identify relevant studies. Randomized controlled trials of N-acetylcysteine in hospitalized patients receiving contrast were included. Studies were excluded if they did not report change in creatinine or incidence of contrast-induced nephropathy at 48 hours. MEASUREMENTS AND MAIN RESULTS: Nine randomized controlled trials satisfied all inclusion criteria and were included in the analysis. The difference in mean change in creatinine between the N-acetylcysteine-treated group and controls was -0.27 mg/dl (95% confidence interval [CI], -0.43 to -0.11). The relative risk of developing contrast-induced nephropathy was 0.43 (95% CI, 0.24 to 0.75) in subjects randomized to N-acetylcysteine. Significant heterogeneity existed among studies, suggesting differences in patient populations or study methodology not identified by sensitivity analyses. The incidence of dialysis was rare (0.2%). CONCLUSIONS: Our findings suggest that N-acetylcysteine helps prevent declining renal function and contrast-induced nephropathy. While N-acetylcysteine is inexpensive and nontoxic, undeviating insistence for dosing at least 12 hours in advance of contrast exposure may delay diagnostic and therapeutic procedures. Future studies are needed to address the longer-term clinical outcomes and cost-effectiveness of this agent.     

Role of N-acetylcysteine in prevention of contrast-induced nephropathy after cardiovascular procedures: a meta-analysis

BACKGROUND: Contrast-induced nephropathy is one of the common causes of acute renal insufficiency after cardiovascular procedures. HYPOTHESIS: The objective of this paper was to analyze the published data on the usefulness of N-acetylcysteine in the prevention of contrast-induced nephropathy after these procedures. METHODS: Trials were selected if they were prospective, randomized, controlled, had selected patients with impaired renal function, used low-osmolality, nonionic contrast media intra-arterially, administered a total of four doses of N-acetylcysteine in addition to intravenous saline hydration, and had contrast-induced nephropathy as their primary outcome. Contrast-induced nephropathy was defined as an increase in serum creatinine concentration by >0.5 mg/dl or a 25% increase above baseline at or within 48 h post procedure. Meta-analysis was performed using the Fisher's Combined Test with a measure of effect size. The magnitude of the N-acetylcysteine effect was estimated using random-effects models. Homogeneity was evaluated using the chi-square test of homogeneity and standard Q statistic. Reporting bias was explored by the Rosenthal method. RESULTS: The Fisher's Combined Test was significant at p < 0.005 in favor of N-acetylcysteine. The size of the N-acetylcysteine effect was to reduce contrast-induced nephropathy by 20%. There was a 62% relative risk reduction in contrast-induced nephropathy with N-acetylcysteine using a fixed-effects model, and a 70% relative risk reduction using the random-effects model. In addition, we found that 27 unpublished trials showing no effects of N-acetylcysteine would exist to overturn the combined significance of p < 0.005 of the five trials in our meta-analysis. CONCLUSION: Oral administration of N-acetylcysteine in addition to intravenous saline hydration has a beneficial effect in the prevention of contrast-induced nephropathy after cardiovascular procedures in patients with impaired renal function.