Effect of N-Acetylcysteine Combined with Lung Rehabilitation Therapy on Exercise Endurance and Quality of Life of Patients with Rheumatoid Arthritis-Related Interstitial Lung Disease

Objective:To explore the effect of N-acetylcysteine combined with lung rehabilitation therapy on exercise endurance and quality of life in patients with rheumatoid arthritis-related interstitial lung disease(RA-ILD).Methods:Fifty-six patients with RA-ILD admitted to Xijing Hospital from May 2022 to January 2024 were randomly divided into two groups:a non-rehabilitation group and a pulmonary rehabilitation group,with 28 patients in each group.Both groups received routine treatment.Additionally,the non-rehabilitation group received N-acetylcysteine treatment,while the lung rehabilitation group received lung rehabilitation treatment in addition to N-acetylcysteine.The improvement in exercise endurance and dyspnea between the two groups after treatment was compared and the quality of life of the patients was observed.Results:After treatment,the exercise endurance score in the lung rehabilitation group(335.67±45.29)was higher than that in the non-rehabilitation group(P<0.05).The dyspnea score in the lung rehabilitation group(0.72±0.16)was lower than that in the non-rehabilitation group(P<0.05).Additionally,FVC(3.18±0.58 L),FEV1(2.28±0.56 L),FEV1/FVC(69.69±5.56),and DLCO(60.53±5.92 mL/mmHg/min)were higher in the lung rehabilitation group compared to the non-rehabilitation group after treatment(P<0.05).Conclusion:Lung rehabilitation therapy combined with N-acetylcysteine treatment can effectively improve dyspnea symptoms,lung function,and exercise endurance in patients with RA-ILD.This approach helps to improve patient’s quality of life and is beneficial for their prognosis.

N-Acetylcysteine Amide(NACA) Reduces Cell Death after Oxidative Stress in a Porcine Embryonic Kidney Cell Line

Introduction: Oxidative stress may have detrimental effects on different structures of the cells, such as the DNA. Recently, we have published a study demonstrating that N-Acetylcysteine amide (NACA) displayed anti-inflammatory properties on the brain after exposure to oxidative stress in an established neonatal piglet model, imitating perinatal asphyxia. As different clinical studies have shown an association between the severity of hypoxic-ischemic encephalopathy and damage of the kidneys, we investigated a possible protective effect of NACA against H2O2-induced oxidative stress using a porcine epithelial-like embryonic kidney cell line (EFN-R). Objective: To investigate a potential protective effect of NACA on cells of a porcine embryonic kidney cell line exposed to H2O2. Methods: We subjected the cells to different concentrations of H2O2 for variable time periods, seeking the optimal dose-response for the experiments. Based on the results of these investigations, we exposed the cells to 100 μMol of H2O2 and/or 750 μM of NACA for 24 hours. Some of the cells would receive NACA either one hour before or one hour after exposure to H2O2. Results: The viability of the investigated EFN-R cells revealed that both, the group treated with NACA before exposure to H2O2 and the group treated with NACA after exposure to H2O2, exhibited significantly higher cell viability compared to the H2O2 group (p < 0.001 and p < 0.01, respectively). Discussion: The increased viability of the cells may indicate that NACA could play an important role in reducing oxidative stress. Taking the results from our previous study into consideration, our findings may strengthen the theory that NACA may have organ protective properties for neonates exposed to oxidative stress.

Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation, Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries

Objective To evaluate the antagonistic effects of N-acetylcysteine(NAC)on mitogen-activated protein kinases(MAPK)pathway activation,oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter(PM2.5).Methods Forty eight male Wistar rats were randomly divided into six groups:blank control group(C1),water drip control group(C2),PM2.5 exposed group(P),low-dose NAC treated and PM2.5 exposed group(L),middle-dose NAC treated and PM2.5 exposed group(M),and high-dose NAC treated and PM2.5 exposed group(H).PM2.5 suspension(7.5 mg/kg)was administered tracheally once a week for four times.NAC of 125 mg/kg,250 mg/kg and 500 mg/kg was delivered intragastrically to L,M and H group respectively by gavage(10 ml/kg)for six days before PM2.5 exposure.The histopathological changes and human mucin 5 subtype AC(MUC5AC)content in lung tissue of rats were evaluated.We investigated IL-6 in serum and bronchoalveolar lavage fluid(BALF)by Enzyme-linked immunosorbent assay(ELISA),MUC5AC in lung tissue homogenate by ELISA,glutathione peroxidase(GSH-PX)in serum and BALF by spectrophotometry,and the expression of p-ERK1/2,p-JNK1/2 and p-p38 proteins by Western blot.All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells.Rats receiving NAC treatment showed less histological destruction and mucus secretion.Of P,L,M and H group,MUC5AC in lung tissue,IL-6 in serum and BALF were higher than controls(C1 and C2)(all P<0.05),with the highest levels found in the P group and a decreasing trend with increase of NAC dose.The activity of GSH-PX in serum and BALF of PM2.5 exposed rats(P,L,M and H)was lower than that of controls(all P<0.05),with higher activities found in NAC treated rats(L,M,and H),and an increasing trend with increase of NAC dose.The expressions of p-ERK1/2,p-JNK1/2 and p-p38 proteins in PM2.5 exposed lung tissue(P,L,M and H)was higher than controls(all P<0.05),with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation,lung oxidative stress and inflammatory injury induced by PM2.5 in rats.

桑树NAC基因家族鉴定与生根粉处理下表达模式分析

【目的】探究桑树NAC基因家族的生物信息学特征,并研究1000 mg·L^(-1)生根粉(ABT)处理对该基因产生的影响,为深入研究桑树NAC转录因子的功能提供依据。【方法】利用生物信息学方法对川桑NAC基因家族进行基因鉴定,并分析其理化性质、保守基序、顺式作用元件、系统进化树、蛋白三级结构及互作关系,并选用‘果桑大十’作为试验材料,经ABT处理后,分析其4个时期(10、20、30、40 d)NAC基因家族的表达模式。【结果】桑树NAC基因家族共有92个成员,分为22个亚家族,亚家族成员广泛分布于细胞核,且具有相似的保守结构。顺式作用元件分析表明,桑树NAC基因家族对激素具有较强的响应能力。蛋白三级结构显示同一亚家族的蛋白空间结构相似,且功能相同,这可能与其进化同源性有关。ABT处理后,NAC基因家族的表达水平整体呈上升趋势,而MnNAC91、MnNAC67、MnNAC28在对照组(CK)中呈现较高的表达水平。【结论】NAC基因家族功能相对稳定,在整个进化过程中无明显变化;ABT可促进NAC基因家族表达,尤其是MnNAC75、MnNAC104、MnNAC7、MnNAC30、MnNAC101、MnNAC83、MnNAC102具有较高的同源性,并与拟南芥的结构功能相似,推测对抗干旱胁迫有一定作用。

养正透邪祛毒法联合NAC方案化疗对三阴性乳腺癌患者疗效、T细胞亚群及癌因性疲乏的影响

目的:探讨养正透邪祛毒法联合NAC方案(多西他赛+表柔比星+环磷酰胺)化疗对三阴性乳腺癌患者疗效、T细胞亚群及癌因性疲乏的影响。方法:选取2022年6月至2023年6月该院诊治的三阴性乳腺癌患者100例,根据随机数字表法分为对照组和观察组,各50例。对照组患者给予NAC方案治疗,观察组患者给予口服自拟养正透邪祛毒方与NAC方案联合治疗。观察两组患者的疗效、T淋巴亚群、炎症因子、癌因性疲乏水平及不良反应发生情况。结果:观察组患者的总有效率为82.00%(41/50),明显高于对照组的58.00%(29/50),差异有统计学意义(P<0.05)。治疗后,两组患者CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、白细胞介素(IL)12和IL-2水平均较治疗前升高,且观察组患者较对照组更高;两组患者CD8^(+)、肿瘤坏死因子α和可溶性白细胞介素-2受体水平,躯体、认知和情感疲乏评分均较治疗前降低,且观察组患者较对照组更低,上述差异均有统计学意义(P<0.05)。观察组、对照组患者的不良反应发生率分别为24.00%(12/50)、28.00%(14/50),差异无统计学意义(P>0.05)。结论:养正透邪祛毒法与NAC方案化疗联合治疗三阴性乳腺癌患者,可明显提高疗效,改善T细胞亚群水平,降低炎症反应,改善癌因性疲乏状况,安全性佳。

N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes

Cadmium （Cd） is a reproductive toxicant that induces germ cell apoptosis in the testes. Previous studies have demonstrated that endoplasmic reticulum （ER） stress is involved in Cd-induced germ cell apoptosis. The aim of the present study was to investigate the effects of N-acetylcysteine （NAC）, an antioxidant, on Cd-induced ER stress and germ cell apoptosis in the testes. Male CD-1 mice were intraperitoneally injected with CdCl2 （2.0 mg kg^-1）. As expected, acute Cd exposure induced germ cell apoptosis in the testes, as determined by terminal dUTP nick-end labelling （TUNEL）. However, the administration of NAC alleviated Cd-induced germ ceil apoptosis in the testes. Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 （GRP78）, an important ER molecular chaperone. Moreover, NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2a （elF2a）, a downstream target of the double-stranded RNA-activated kinase-like ER kinase （PERK） pathway. In addition, NAC blocked the Cd-induced activation of testicular X binding protein （XBP）-1, indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response （UPR）. Interestingly, NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein （CHOP） and phosphorylation of c-Jun N-terminal kinase （.INK）, two components of the ER stress-mediated apoptotic pathway. In conclusion, NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.

桃基因 PpNAC 的鉴定及其在不同发育时期的表达分析

【目的】鉴定影响桃果实成熟的PpNAC基因,并分析其在桃果实不同发育时期的表达量变化,为解析桃果实成熟的分子机制奠定基础。【方法】通过对桃不同组织部位的转录组分析,从115个PpNAC基因家族成员中筛选在果实中特异表达的PpNAC基因,进一步进行生物信息学分析、蛋白互作分析和表达分析,筛选可能影响桃果实成熟的PpNAC基因。【结果】筛选到16个在桃果实中高表达的PpNAC基因,其在桃的8条染色体上都有分布,蛋白相对分子质量和等电点差异较大。基因编码区均含有NAM保守结构域和motif1~6,含有3~8个外显子,2~7个内含子,启动子中脱落酸响应元件和茉莉酸响应元件相对较多。此外,通过与已报道成熟相关NAC蛋白PpNAC1的互作筛选,得到4个与PpNAC1互作的PpNAC蛋白。进一步的表达分析表明,这4个PpNAC基因在果实成熟起始期和成熟后期表达量达到最高。【结论】PpNAC基因可能参与调控桃果实成熟。

紫花苜蓿耐盐性相关NAC转录因子的挖掘及表达分析

NAC(NAM,ATAF1/2,CUC2)是植物特有的一类转录因子家族,可调控植物响应盐胁迫。本研究基于盐胁迫下紫花苜蓿(Medicago sativa L.)耐盐品种GIB和盐敏感品种LS根和叶的转录组数据,通过生物信息学方法筛选出17个差异表达的MsNAC转录因子家族成员,并对其序列特征、系统进化、顺式作用元件及盐胁迫下的表达模式等进行分析。结果显示,17个MsNACs均具有NAC典型的NAM结构域,且蛋白结构相似。系统进化分析将17个MsNACs分成8个亚族,各亚组成员具有高度相似的保守基序。顺式作用元件分析发现,有15个MsNACs具有ABA响应顺式元件ABRE。转录组数据表达模式分析与RT-qPCR验证结果显示MsNAC1,MsNAC2,MsNAC35,MsJUB1和MsNAC40基因在盐处理下GIB叶中上调表达,在LS叶中下调或者未发生变化,推测这些基因参与调控紫花苜蓿的耐盐反应。本研究为进一步研究紫花苜蓿NAC转录因子响应盐胁迫功能提供参考依据。

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: An endoscopist-blinded, prospective, randomized study

AIM： To assess the efficacy of premedicaton with pronase or N-acetylcysteine （NAC） at 20 min before upper gastrointestinal （UGI） endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test. METHODS： A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility （MV） with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility （TMV） score. Identification of Hpylori was performed using CLO test, histology, and serology. RESULTS： The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water （P 〈 0.001 and P 〈 0.01, respectively）. The group with NAC had a significantly lower TMV score than the group with gascon （P 〈 0.01） and a trend of a lower MV score than the group with gascon water （P = 0.06）. The THV score did not significantly differ between the group with pronase and the group with NAC （P = 0.39 and P = 0.14, respectively）. The sensitivity and specifidty of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together.CONCLUSION： Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.

紫花苜蓿NAC基因家族鉴定及在非生物胁迫下的表达模式分析

NAC是植物特有转录因子,在调控植物生长发育及响应非生物胁迫等方面发挥作用。为挖掘紫花苜蓿(Medicago sativa)响应干旱等非生物胁迫的NAC转录因子,本研究利用生物信息学方法在‘中苜4号’紫花苜蓿基因组中鉴定出143个NAC家族转录因子。研究表明,紫花苜蓿MsNAC基因在染色体上不均匀分布,MsNAC基因存在片段重复,并与大豆(Glycine max(Linn.)Merr.)、蒺藜苜蓿(Medicago truncatula)存在共线性关系,基因保守基序及基因结构分析表明MsNAC基因多数含有Motif1,Motif3保守基序及3~6个外显子。大多数MsNAC蛋白定位于细胞核中。系统进化树分析结果表明MsNACs聚类为8个亚家族。顺式作用元件分析表明MsNAC基因含有响应干旱及脱落酸、生长素等顺式作用元件。荧光定量分析结果显示部分MsNAC基因响应干旱、盐胁迫及脱落酸处理,大部分MsNAC候选基因在干旱、盐及ABA处理后上调表达。本研究结果可为紫花苜蓿抗旱、耐盐分子育种提供候选基因。

Efficacy of premedication with activated Dimethicone or N-acetylcysteine in improving visibility during upper endoscopy

AIM:To assess the efficacy of N-acetylcysteine(NAC) and activated Dimethicone in improving endoscopic mucosal visibility.METHODS:A total of 148 patients were randomly allocated into four groups to receive one of the following premedications:group A:100 mL water alone;group B:activated Dimethicone plus water(up to 100 mL);group C:NAC plus water(up to 100 mL);and group D:activated Dimethicone and NAC plus water(up to 100 mL).A single endoscopist blinded to the patients group assessed the gastric mucosal visibility scores(range 1-4) at four sites.The sum of the scores from the four sites was considered as the total mucosal visibility score(TMVS).RESULTS:The patients in group B showed a significantly lower TMVS than those of groups A and C(P < 0.001).The TMVS in patients of group D was significantly lower than that of groups A and C(P < 0.001).The TMVS did not significantly differ between groups B and D(P > 0.05).The difference between TMVS of groups C and A was not significant(P > 0.05).CONCLUSION:Premedication with activated Dimethicone 20 min prior to the upper endoscopy leads to the best visibility.NAC does not improve visualization by itself.

N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice

BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-a and plasma ALT increased continuously in the l/R group at I and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

N-acetylcysteine does not prevent post-endoscopic retrograde cholangiopancreatography hyperamylasemia and acute pancreatitis

AIM： Acute pancreatitis （AP） is the most common and often severe complication of endoscopic retrograde cholangiopancreatography （ERCP）. The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals. N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine （ACC） can reduce the severity of disease in experimental model of AP. METHODS： One hundred and six patients were randomly allocated to two groups. Fifty-five patients were given N-acetylcysteine （two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv, twice a day for two days after the ERCP）. The control group consisted of 51 patients who were given iv. isotonic saline twice a day for two days after the ERCP. Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure. The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity. RESULTS： There were no significant differences in the rate of post-ERCP pancreatitis between two groups （10 patients overall, 4 in the ACC group and 6 in the controlgroup）. There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group. CONCLUSION： N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis, as well as on serum and urine amylase activity.

观赏植物NAC转录因子的研究进展

NAC转录因子家族在调节植物的生长发育中发挥着重要的作用,在模式植物、作物中已进行了大量研究,但是在观赏植物中的研究还缺乏系统性的梳理和探讨。本综述介绍了NAC转录因子的结构和分类,并梳理了2004-2023年NAC转录因子在观赏植物器官生长发育和胁迫响应上的生物学功能研究,其中观赏植物器官生长发育主要集中在叶缘形态建成、花器官发育、叶片衰老、花瓣衰老、种球休眠5个方面,胁迫响应则集中在干旱、盐、碱、冷、热等非生物胁迫,在生物胁迫中报道较少。最后,鉴于观赏植物NAC转录因子大部分都还停留在生物信息学分析以及表达模式分析等功能初探阶段,本文在结合观赏植物全基因组测序继续开展NAC转录因子鉴定研究、挖掘观赏植物中与模式植物存在不同作用机制的NAC转录因子、解析观赏植物NAC转录因子与其他转录因子间的调控网络、加快利用推进基因工程或编辑技术开展观赏植物的分子育种工作等4个方面,对未来NAC转录因子在观赏植物中的研究提出了展望。

N-acetylcysteine attenuates reactive-oxygen-speciesmediated endoplasmic reticulum stress during liver ischemia-reperfusion injury

AIM: To investigate the effects of N-acetylcysteine (NAC) on endoplasmic reticulum (ER) stress and tissue injury during liver ischemia reperfusion injury (IRI).

N-acetylcysteine treats intravenous amiodarone induced liver injury

We report a case of intravenous(IV) amiodarone drug induced liver injury(DILI).The patient received IV N-acetylcysteine(NAC) which resulted in a rapid improvement in liver enzymes.While the specific mechanisms for the pathogenesis of IV amiodaroneDILI and the therapeutic action of IV NAC are both unknown, this case strongly implies at least some commonality.Because IV amiodarone is indicated for the treatment of serious cardiac arrhythmias in an intensive care unit setting, some degree of ischemic hepatitis is likely a cofactor in most cases.

马铃薯StNAC6基因克隆及干旱胁迫表达分析

NAC对植物种子发育、细胞分裂分化、侧根形成等都有直接影响,它与DNA元件相结合发挥作用,能够有效提高植物的抗逆性。通过PCR方法从马铃薯冀张薯8号中克隆获得了1个StNAC6基因,并对StNAC6基因进行生物信息学分析,包含序列比对、理化性质预测、进化分析等。使用冀张薯8号组培苗作为试验材料,用浓度为10%、15%和20%的聚乙二醇6000(PEG-6000)处理0、6、12、24 h后,分析干旱胁迫下的表达模式,并在马铃薯开花期,采取不同的组织(花、根、茎、叶、块茎、葡匐茎)进行组织表达分析。结果表明,马铃薯NAC6基因全长为876 bp,共编码291个氨基酸,包含1个NAM结构域;等电点为7.04,相对分子量为33.61915 ku;StNAC6蛋白均含有丝氨酸、苏氨酸和酪氨酸3种氨基酸磷酸化位点,属于不稳定亲水性蛋白;StNAC6第74、262位氨基酸存在N-糖基化位点;预测StNAC6定位于细胞核。荧光定性PCR结果显示,在不同含量PEG胁迫处理下,马铃薯StNAC6基因的相对表达量不相同,存在明显差异,说明该基因参与干旱应答响应;StNAC6基因在马铃薯茎、花中的相对表达量最高,说明其可能参与马铃薯生长调控。研究结果可为今后深入探究马铃薯NAC6转录因子的功能和调控机制奠定基础。

Role of N-acetylcysteine in rifampicin-induced hepatic injury of young rats

AIM, To study the role of N-acetylcysteine （NAC） as a protective agent in rifampicin （RMP）-induced oxidative hepatic injury of young rats. METHODS： Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC （100mg/kg body weight/day） was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P4se, superoxide dismutase （SOD）, catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS： RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol （GSH） status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION. NAC protects young rats against RMP- induced oxidative hepatic injury.

Neuroprotective effects of combined lead and cadmium,as well as N-acetylcysteine,on cerebral cortical neurons following lipid peroxidation injury

BACKGROUND： Studies have reported the antioxidant effects of lead and cadmium in the central nervous system, but very few have addressed the combined toxicity of lead and cadmium. The mechanisms by which these combined heavy metals are toxic, as well as how to protect cells from these agents, remains poorly understood. OBJECTIVE： Primary cultured rat cortical neurons were used to determine the effects of combined lead and cadmium on levels of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT）, and acetylcholinesterase （ACHE）, as well as malondialdehyde （MDA）, and to evaluate the neuroprotective effects of N-acetylcysteine （NAC）. DESIGN, TIME AND SETTING An in vitro toxicological observation was performed at the Comparative Medicine Center of Yangzhou University from August 2007 to April 2008. MATERIALS： Lead acetate, cadmium acetate, and NAC were purchased from Sigma-Aldrich （St. Louis, USA）. Commercial kits of GSH-Px, SOD, CAT, ACHE, and MDA were purchased from Nanjing Jiancheng Bioengineering Institute, Nanjing, China. METHODS： The cerebral cortical neurons were isolated from newborn Sprague dawley rats at 24 hours after birth and primary cultured for 6 days. Thereafter, the cells were treated with a range of cadmium doses （0, 5.0, and 10.0μmol/L）, lead doses （0, 1.0, and 2.0 μmol/L）, or a combination of the two for 12 hours at 37℃in a 5% CO2 incubator, respectively. In addition, the cells were incubated with different doses of cadmium and/or lead and （0 and 50 μmol/L） NAC for 12 hours to assess the protective effects on cell survival. MAIN OUTCOME MEASURES： The activity of SOD, GSH-Px, CAT, and ACHE, as well as MDA content, in the cell lysates was detected using commercial kits. RESULTS： At 12 hours after treatment, compared to the control group, activity of GSH-Px, SOD, and AChE in the lead, cadmium, or combined treated cells was significantly decreased with increasing doses of cadmium/or lead （P 〈 0.05）, but CAT activity and MDA levels were significantly increased （P 〈 0.05）. The combination of cadmium and lead led to higher levels of toxicity than individual exposure. CONCLUSION： The degree of oxidative damage increased when the two heavy metals were combined. NAC protected neonatal cortical neurons by increasing activity of anti-oxidative enzymes and reducing lipid peroxidation, but the reduction was not statistically significant.