吡咯烷二硫代氨基甲酸盐对糖尿病大鼠血管内皮功能不全的影响及其机制

目的探讨吡咯烷二硫代氨基甲酸盐(PDTC)对糖尿病大鼠血管内皮依赖性舒张功能损害的保护作用及其机制。方法雄性SD大鼠一次性ip给予链脲佐菌素60 mg·kg-1制备糖尿病模型,通过饮水中给予PDTC 10 mg·kg-1,连续治疗8周。检测血糖、血脂和血清内源性一氧化氮合酶(NOS)抑制物非对称性二甲基精氨酸(ADMA)浓度。用含有人二甲基精氨酸二甲胺水解酶2(h DDAH2)基因的重组腺病毒(Ad5CMV-h DDAH2)体外感染糖尿病大鼠血管环,分别检测感染前后血管环对乙酰胆碱诱导的最大舒张反应(Emax)、半数有效量(EC50)及血管组织DDAH活性。结果与正常组比较,糖尿病大鼠血糖明显升高,血清ADMA浓度从正常组的(1.14±0.26)μmol·L-1升至(2.18±0.52)μmol·L-1(P<0.01);血管组织DDAH活性也从正常组的(0.10±0.02)U·g-1蛋白降至(0.05±0.01)U·g-1蛋白(P<0.01);血管内皮依赖性舒张功能损伤,表现为Emax由正常组的(93.6±4.4)%降至(50.8±4.9)%(P<0.01),EC50由正常组的(88±22)nmol·L-1升至(240±45)nmol·L-1(P<0.01)。PDTC治疗降低血糖和血清ADMA浓度分别至(13.2±3.5)mmol·L-1和(1.40±0.25)μmol·L-1(P<0.01),增加血管DDAH活性至(0.08±0.02)U·g-1蛋白(P<0.01),改善内皮依赖性血管舒张功能,使Emax增至(84.6±4.5)%,EC50降至(134±27)nmol·L-1(P<0.01)。糖尿病大鼠血管转染DDAH2基因后,血管DDAH活性及Emax和EC50的变化与PDTC治疗组相似。结论 PDTC对糖尿病大鼠血管内皮依赖性舒张功能具有明显的保护作用,其机制可能与上调血管DDAH活性,降低内源性NOS抑制物ADMA蓄积有关。     

川东獐牙菜素A保护溶血性磷脂酰胆碱诱导的内皮细胞损伤

目的 观察川东獐牙菜素A对溶血性磷脂酰胆碱(LPC)诱导的血管内皮细胞损伤的保护。方法 ①检测Cu2+诱导的低密度脂蛋白(LDL)氧化和二苯代苦味肼基自由基(DPPH)反应。②在大鼠离体胸主动脉环,检测乙酰胆碱诱导的内皮依赖性舒张反应。③培养内皮细胞,测定培养液中乳酸脱氢酶(LDH)、丙二醛(MDA)、一氧化氮(NO)和非对称性二甲基精氨酸(ADMA)浓度及细胞内二甲精氨酸二甲胺水解酶(DDAH)活性。结果①川东獐牙菜素A能显著抑制Cu2+诱导的LDL氧化和清除DPPH。②川东獐牙菜素A(10或30μmol·L-1)能改善LPC(5 mg·L-1)所致血管内皮依赖性舒张功能损伤。⑧川东獐牙菜素A(1、3或10μmol·L-1)能抑制LPC(5 mg·L-1)诱导的培养液中LDH和MDA浓度的降低以及NO浓度的增加;川东獐牙菜素A(3或10 μmol·L-1)能显著抑制LPC诱导的ADMA水平升高;川东獐牙菜素A(10μmol·L-1)能显著增加DDAH活性。结论 川东獐牙菜素A对LPC所致的血管内皮细胞损伤有保护作用,其作用与增加DDAH活性和降低AD-MA浓度有关。     

罗格列酮对糖尿病大鼠血管内皮损伤的保护作用与一氧化氮合酶抑制物的关系

目的研究罗格列酮对链脲佐菌素(STZ)诱导的1型糖尿病大鼠血管内皮损伤的保护作用与内源性一氧化氮合酶(NOS)抑制物的关系.方法 SD大鼠单次腹腔注射STZ(60 mg·kg-1)诱发实验性1型糖尿病,检测血中血糖、血脂、非对称性二甲基精氨酸(ADMA)、肿瘤坏死因子-α(TNF-α)含量,并观察离体主动脉环的内皮依赖性舒张反应;ADMA孵育内皮细胞,检测细胞培养液中TNF-α.结果实验性1型糖尿病大鼠胸主动脉对乙酰胆碱(Ach)诱导的血管内皮依赖性舒张效应显著减弱,血中TNF-α与ADMA浓度显著升高,罗格列酮能显著改善糖尿病大鼠内皮依赖性舒张功能,降低血中TNF-α浓度,但不影响血脂、血糖与ADMA水平.在培养的人脐静脉内皮细胞,ADMA能显著升高培养液中TNF-α水平,罗格列酮(10,30 μmol·L-1)能显著抑制TNF-α水平的升高.结论罗格列酮能改善链脲佐菌素诱导的1型糖尿病大鼠血管内皮依赖性舒张功能,其机制与抑制ADMA的致炎作用有关.     

瓜蒌皮提取物对大鼠血管内皮损伤的保护作用

目的研究瓜蒌皮提取物（EPT）对低密度脂蛋白（LDL）诱导的血管内皮损伤的保护作用。方法 48只SD大鼠在乙醚麻醉下,舌下静脉注射人血清LDL（4mg/kg）诱发血管内皮功能损伤。检测血中非对称性二甲基精氨酸（ADMA）、丙二醛（MDA）、一氧化氮（NO）和肿瘤坏死因子-α（TNF-α）的含量。结果单次静注LDL（4mg/kg）显著增加血液中ADMA、MDA和TNF-α水平,降低血液中NO水平。用水和70%乙醇洗脱的瓜蒌皮提取物能显著抑制ADMA、MDA和TNF-α浓度升高及增加血液中NO水平。结论瓜蒌皮提取物对LDL诱导的血管内皮细胞损伤有保护作用,其保护作用与降低ADMA浓度有关。     

卡维地洛对氧化低密度脂蛋白诱导血管内皮细胞ADMA-DDAH系统的影响

目的 观察卡维地洛对氧化低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)二甲基精氨酸-二甲基赖氨酸水解酶(DDAH)活性及表达的影响,以探讨卡维地洛对内源性一氧化氮合酶抑制物不对称二甲精氨酸(ADMA)代谢机制的影响.方法 采用改良的Jaffe法培养原代人脐静脉内皮细胞(HUVECs),取生长良好的3～6代HUVECs用于实验,分为(1)空白对照组:加DMEM培养液;(2)ox-LDL组:加入ox-LDL(100 mg/L,150 mg/L);(3)ox-LDL 卡维地洛组:同时加入150 mg/L ox-LDL及卡维地洛(10 μmol/L)共孵24h后,检测上清液中NO、NOS活性、ADMA含量、L-胍氨酸(L-cit)浓度,采用Western blotting测定细胞裂解液中二甲基精氨酸-二甲基赖氨酸水解酶(DDAH)的蛋白表达.结果 ox-LDL条件培养下,内皮细胞的代谢产物ADMA、ET的量均较空白对照组高,而NO的量及NOS的活性减少;反应DDAH酶活性的L-cit浓度显著降低,且有浓度依赖性,而DDAH的表达无明显变化.卡维地洛干预后,ADMA、ET的量较ox-LDL组降低,NOS活性及NO增加,L-cit浓度明显升高.结论 ox-LDL诱导下,内皮损伤ADMA的增加与DDAH的活性减弱有关,而与DDAH的表达无关.卡维地洛通过增加DDAH活性促进ADMA代谢,使NOS活性增高,抑制ox-LDL对内皮功能的损伤.     

洛伐他汀对低密度脂蛋白损伤血管内皮的保护作用

目的：探讨洛伐他汀对低密度脂蛋白所致血管内皮功能损伤的保护作用及可能的机制．方法：一次性从大鼠舌下静脉注射天然低密度脂蛋白(n-LDL 4mg／kg),在舌下静脉注射n-LDL之前大鼠腹腔注射洛伐他汀(2或4mg／kg),每天一次,连续五天．注射n-LDL后48小时检测乙酰胆碱诱导的血管内皮依赖性舒张(EDR)及血清一氧化氮(N0)、丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活性．结果：一次注射n-LDL导致了EDR、血清NO水平及SOD活性明显降低,MDA的浓度明显增高。预先给予洛伐他汀能明显减轻LDL引起的EDR的抑制和血清NO水平及SOD活性的降低,减少MDA的生成,左旋硝基精氨酸(L-NNA)减弱洛伐他汀对血管内皮的保护作用．结论：洛伐他汀对LDL损伤的血管内皮具有保护作用,可能与保护内皮依赖性松弛因子和抗氧化作用有关。     

同型半胱氨酸对内皮细胞一氧化氮合酶活力及基因表达的影响

目的 观察同型半胱氨酸(Hcy)对培养的人脐静脉内皮细胞(HUVEC)一氧化氮合酶(eNOS)活力及其基因表达的动态影响.方法 10、30、100、300 μmol · L-1Hcy与HUVEC分别培养24、48、72 h后,用HPLC测定细胞内不对称二甲基精氨酸(ADMA)的含量,反转录聚合酶链反应(RT-PCR)检测细胞内eNOS mRNA的表达,并分别测定细胞二甲基精氨酸二甲基氨基水解酶(DDAH)、eNOS的活力和NO的含量.结果 HUVEC经不同浓度Hcy分别处理24、48、72 h后,其细胞内ADMA聚积增多,DDAH活性和eNOS活力降低,NO生成减少,且呈时间和浓度依赖性.但只有100 μmol · L-1 Hcy与HUVEC作用72 h时,才引起eNOS mRNA表达的减少.结论 Hcy对内皮功能的损伤可能通过抑制DDAH活性,引起ADMA聚积,从而降低eNOS活力,导致NO生成减少.此外,eNOS mRNA表达的抑制也是Hcy诱导的内皮功能障碍的机制之一.     

卡托普利对动脉粥样硬化家兔血管内皮功能的保护作用及其机制

目的探讨卡托普利对动脉粥样硬化(AS)家兔血管内皮功能和形态的保护作用及其机制。方法采用高脂、高胆固醇饲料饲养家兔制备AS模型的同时口服给予卡托普利8 mg·kg-1,每天1次,连续12周;HE染色观察血管组织形态,检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL);高效液相色谱测定血清非对称性二甲基精氨酸(ADMA)浓度;用重组编码人类二甲基精氨酸-二甲胺水解酶2(hDDAH2)基因的腺病毒感染AS家兔离体胸主动脉环2 h,检测对乙酰胆碱累积浓度诱导的最大舒张反应(Emax)、半数有效量(EC50)及DDAH活性。结果与正常组比较,高脂模型家兔胸主动脉内膜和中膜增厚,血清TC,TG和LDL水平升高;血清ADMA浓度升高至(2.24±0.28)μmol·L-1(P<0.01);血管壁DDAH活性降至(0.048±0.007)U·g-1蛋白(P<0.01);Emax降低至(56±8)%(P<0.01),EC50升高至(158±52)nmol·L-1(P<0.01)。与AS模型组比较,卡托普利治疗组血管内膜增厚减轻,血脂无明显降低,血清ADMA浓度显著降低至(1.37±0.23)μmol·L-1(P<0.01),血管DDAH活性增加至(0.084±0.013)U·g-1蛋白(P<0.01),内皮依赖性血管舒张功能改善,Emax增加至(88±4)%(P<0.01),EC50降低至(90±35)nmol·L-1(P<0.01)。AS模型血管转染DDAH2基因后,血管Emax回升至(88±4)%,EC50降低至(98±42)nmol·L-1,DDAH活性升高至(0.112±0.017)U·g-1蛋白,与卡托普利治疗组相似。结论卡托普利对AS家兔血管形态和内皮功能具有明显保护作用,其机制可能与增加血管DDAH活性,降低内源性ADMA浓度有关。     

花卷茶提取物对高胆固醇血症大鼠血脂和内皮功能的影响

目的研究花卷茶提取物对高胆固醇血症大鼠血脂和内皮功能的影响及机制。方法雄性SD大鼠高脂饲养4周诱发高胆固醇血症,其中实验组在高脂饲料饲养2周后开始每日灌胃给予不同剂量的花卷茶系列之十两茶水提物（50、100和200mg.kg-1）,持续2周。实验结束后,颈动脉取血测定血脂、一氧化氮（NO）、非对称二甲基精氨酸（ADMA）和丙二醛（MDA）含量;分离胸主动脉检测血管内皮依赖性舒张功能。结果十两茶提取物能呈剂量依赖性降低高脂血症大鼠血清总胆固醇和低密度脂蛋白及甘油三酯水平。十两茶提取物能显著改善高脂所诱导的血管内皮舒张功能障碍,降低血浆ADMA和MDA含量以及增加NO水平,且呈剂量依赖性。结论花卷茶系列之十两茶提取物具有降低血脂和保护血管内皮功能作用,其作用与抑制脂质过氧化、调节ADMA/NO系统有关。     

芝麻素对肾性高血压伴高血脂大鼠主动脉舒张功能的影响

目的:探讨芝麻素(Sesamin,Ses)改善肾性高血压伴高血脂大鼠(Rrenal hypertensive-hy-perlipidemia rat,RHHR)主动脉舒张功能损伤的作用机制.方法:RHHR灌服不同剂量Ses(100、33、10 mg·kg-1·d-1)8周后,测定主动脉环对乙酰胆碱(Acetylcholine,ACh)和硝普钠(Sodium nitroprusside,SNP)的舒张反应;测定一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(N-ni-tro-L-arginine-methyl-ester,L-NAME)孵育后,动脉环对ACh的反应并计算一氧化氮(Nitric oxide,NO)活性.结果:与假手术组相比,RH-HR主动脉Ach和SNP诱导的舒张反应显著降低,NO活性减少,Ses治疗8周后能逆转上述作用.结论:Ses降压作用与改善RHHR主动脉内皮依赖性和非内皮依赖性舒张功能损伤有关.     

Theoretical π-π* absorption and circular dichroic spectra of cyclic dipeptides

The dipole interaction model, treated by the partially dispersive normal mode method, is used to calculate circular dichroic spectra of cyclo(Gly-Gly), cyclo (Ala-Gly), cyclo(Ala-Ala), cyclo(Pro-Gly), cyclo(Pro-Ala), cyclo(Pro-Val), cyclo (Pro-D-Val), and cyclo(Pro-Pro) in the amide π-π* absorption band near 190 nm. Assuming a standard backbone geometry, spectra which are in fair to good agreement wth experiment are obtained for these molecules. The spectra are predicted to be sensitive to conformations of Pro and Val side chains. The effects of dipeptide ring folding on calculated CD spectra are mostly consistent with those found by other workers, except that it is found that a planar ring conformation of cyclo (Ala-Ala) and cyclo (Ala-Gly) gives predicted spectra comparable to experiment. The same model gives theoretical absorption spectra consistent with available experimental data.     

Effects of Nitro-L-Arginine on Blood Pressure and Cardiac Index in Anesthetized Rats: A Pharmacokinetic-Pharmacodynamic Analysis

Purpose. Nitric oxide synthase (NOS) inhibitors such as Nitro-L-arginine (L-NA) are being considered for the management of hypotension observed in septic shock. However, little information is available regarding the pharmacokinetic and pharmacodynamic properties of these agents. Our objective was to examine the relationships between L-NA plasma concentration and various hemodynamic effects such as cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) elicited by L-NA administration in rats. Methods. L-NA was infused at doses between 2.5 – 20 mg/kg/hr in anesthetized rats over one hour. Hemodynamic effects and plasma L-NA levels were determined. Results. Infusion of L-NA resulted in dose-dependent increases in MAP and systemic vascular resistance (SVR), decreases in CI, and minimal change in HR. The relationships between the hemodynamic effects and plasma L-NA levels were not monotonic, and hysteresis was observed. Using nonparametric analysis, the equilibration half-time (t_1/2,keo) between plasma L-NA and the hypothetical effect site was determined to be 51.5 ± 6.6 min, 42.4 ± 10.1 min, 43.4 ± 9.0 min for MAP, CI, and SVR, respectively (n = 14). The E_max and EC₅₀ values obtained were + 32.5 ± 8.4 and 2.6 ± 1.3 g/ml for MAP and –52.9 ± 15.6 and 3.7 ± 1.8 g/ml for CI, respectively. Conclusions. Although L-NA can bring about beneficial elevation of MAP, such effect is always accompanied by a stronger effect on CI depression. Dose escalation of L-NA may bring about detrimental negative inotropic effect and loss of therapeutic efficacy.     

The pathogenesis of,and pharmacological treatment for,Canavan disease

1. Download : Download high-res image (184KB)
2. Download : Download full-size image

     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

洛美沙星体内外抗菌活性研究

洛美沙星对革兰氏阴性菌具有强的抑菌活力。对克氏肺炎杆菌的抗菌活性最强,MIC_(50)为0.12mg/L;对痢疾杆菌、产气杆菌、粘质沙雷氏菌、不动杆菌和枸椽酸杆菌的MIC_(50)分别为1和4mg/L。洛美沙星对肠细菌科细菌的活力比诺氟沙星和依诺沙星强2～16倍,明显地比丁胺卡那霉素、庆大霉素强。对金葡球菌MIC_(50)为1mg/L, MRSA对洛美沙星同样敏感。洛美沙星对表葡球菌、链球菌、粪链球菌及肺炎双球菌等的抗菌活性与地氟沙星相似,比诺氟沙星、依诺沙星、丁胺卡那霉素、庆大霉素和头孢三嗪分别强2～4倍。 洛美沙星对小鼠全身感染的疗效优于诺氟沙星。对大肠杆菌、克氏肺炎杆菌和绿脓杆菌感染小鼠iv的ED_(50)分别是0.74、0.13和3.45mg/kg, po的ED_(50)分别是0.94、1.46和6.20mg/kg。     

Protective role of exogenous α-lipoic acid (ALA) on hippocampal antioxidant status and memory function in rat pups exposed to sodium arsenite during the early post-natal period

The present work focussed on the effect of exogenous α-lipoic acid (ALA) administration on retention memory and oxidative stress markers in the hippocampus subsequent to early post-natal exposure of rat pups to sodium arsenite (NaAsO₂). Wistar rat pups were divided into the control groups receiving either no treatment (Ia) or distilled water by intraperitoneal route (i.p.) (Ib) and the experimental groups receiving either NaAsO₂ alone (1.5 and 2.0?mg/kg body wt.) (IIa, IIb) or NaAsO₂ (1.5 and 2.0?mg/kg body wt.) followed by ALA (70?mg/kg body wt.) (IIIa, IIIb) (i.p.) from post-natal day (PND) 4–15. The initial and retention transfer latency (ITL and RTL) was determined on PND 14 and 15 using elevated plus maze. The animals were sacrificed by cervical decapitation (PND 16) and the brains were obtained. The dissected out hippocampus was processed for estimation of oxidative stress markers, glutathione (GSH), and superoxide dismutase (SOD). NaAsO₂ exposure resulted in longer RTL in animal groups IIa and IIb, thereby suggestive of arsenic-induced impairment in retention memory. RTL was significantly shorter in animal groups (IIIa, IIIb) receiving ALA following NaAsO₂, thereby suggestive of improvement in retention memory. GSH and SOD levels were significantly decreased in animals receiving NaAsO₂ alone as against group Ib and administration of ALA following NaAsO₂ increased the levels of hippocampal GSH and SOD. These observations are suggestive of the role of exogenous ALA in ameliorating the adverse effects induced by NaAsO₂ exposure of rat pups on retention memory and oxidative stress markers.     

乙酰吉他霉素临床前药理学研究

乙酰吉他霉素对临床分离的革兰氏阳性球菌有较好的抑菌活力，其对金葡球菌、β－溶血性链球菌、表葡球菌的ＭＩＣ_（５０）分别为１、０．２２和４ｍｇ／Ｌ，对耐红霉素、青霉素的金葡球菌、表葡球菌半数以上较敏感，与吉他霉素相似，但其对革兰氏阴性菌无明显作用。乙酰吉他霉素对小鼠实验性细菌感染有明显保护作用。对金葡球菌、肺炎双球菌感染小鼠口服用药的ＥＤ_（５０）分别为７９．６和２５．１ｍｇ／ｋｇ。其疗效与吉他霉素、麦白霉素、乙酰螺旋霉素相似。乙酰吉他霉素小鼠１次口服的ＬＤ_（５０）＞１５ｇ／ｋｇ，与吉他霉素相比毒性无差异。     

大鼠溃疡性结肠炎模型的实验研究

目的对不同剂量的三硝基苯磺酸（ＴＮＢＳ）引起的大鼠溃疡性结肠炎（ＵＣ）模型进行观察和评价。方法采用一次性直肠注入大鼠ＴＮＢＳ（２５～１５０ｍｇ·ｋｇ－１）的３０％乙醇溶液，引起慢性炎症性肠疾病（ＩＢＤ），３ｗｋ后外死动物对各剂量下动物结肠的重量、髓过氧化物酶（ＭＰＯ）活性及组织形态学变化进行观察和评价。结果ＴＮＢＳ在１００～１５０ｍｇ·ｋｇ－１剂量下引起的ＵＣ肠壁明显增厚，炎症和溃疡至少维持７ｗｋ时间，ＭＰＯ活性值显著性升高，组织学检查发现粘膜及粘膜下层有大量中性粒细胞及淋巴细胞、巨噬细胞、纤维细胞浸润，肉芽组织及隐窝脓肿形成，５０ｍｇ·ｋｇ－１剂量时有一较轻度的损伤。２５ｍｇ·ｋｇ－１时对结肠的重量、ＭＰＯ活性及损伤指数都没有显著性改变（Ｐ＞０．０５）。结论用ＴＮＢＳ引起大鼠实验性ＵＣ，其溃疡和炎症维持一较长时间，这一病理特征为炎症性疾病防治药物的研究提供了条件；本模型的最佳剂量为１００ｍｇ·ｋｇ－１左右     

Dinoflagellate polyether within the yessotoxin, pectenotoxin and okadaic acid toxin groups: Characterization, analysis and human health implications

Diarrhetic Shellfish Poisoning (DSP) is a specific type of food poisoning, characterized by severe gastrointestinal illness due to the ingestion of filter feeding bivalves contaminated with a specific suite of toxins. It is known that the problem is worldwide and three chemically different groups of toxins have been historically associated with DSP syndrome: okadaic acid (OA) and dinophysistoxins (DTXs), pectenotoxins (PTXs) and yessotoxins (YTXs). PTXs and YTXs have been considered as DSP toxins because they can be detected with the bioassays used for the toxins of the okadaic acid group, but diarrhegenic effects have only been proven for OA and DTXs. Whereas, some PTXs causes liver necrosis and YTXs damages cardiac muscle after intraperitoneal injection into mice. On the other hand, azaspiracids (AZAs) have never been included in the DSP group, but they cause diarrhoea in humans. This review summarizes the origin, characterization, structure, activity, mechanism of action, clinical symptoms, method for analysis, potential risk, regulation and perspectives of DSP and associated toxins produced by marine dinoflagellates.     

Latent role of in vitro Pb exposure in blocking Aβ clearance and triggering epigenetic modifications

Both β-amyloid (Aβ) catabolism and epigenetic regulation play critical roles in the onset of neurodegeneration. The latter also contribute to Pb neurotoxicity. The present study explored the role of epigenetic modifiers and Aβ degradation enzymes in Pb-induced latent effects on Aβ overproduction in vitro. Our results indicated that in SH-SY5Y cells exposed to Pb, the expression of NEP and IDE remained declined during the recovery period, accompanied with abnormal increase of Aβ_1-42 and amyloid oligomer. A disruption of selective global post-translational histone modifiers including the decrease of H3K9ac and H4K12ac and the induction of H3K9me2 and H3K27me2 dose dependently was also showed in recovery cells. Moreover, histone deacetylase inhibitor VPA could attenuate latent Aβ accumulation and HDAC activity induced by Pb, which might be by regulating the expression of NEP and IDE epigenetically. Overall, our results suggest sustained reduction of NEP and IDE expression in response to Pb sensitizes recovery SH-SY5Y cells to Aβ accumulation; however, administration of VPA is demonstrated to be beneficial in modulating Aβ clearance.