灰绿黄堇总生物碱对实验性溃疡性结肠炎的作用研究

目的研究灰绿黄堇总生物碱（ACAM）对小鼠结肠炎的作用及其机制。方法实验设正常、模型、柳氮磺胺吡啶组（SASP,520mg/kg）和ACAM组（100、200、400mg/kg）。正常组小鼠饮用蒸馏水,其余组自由饮用4%葡聚糖硫酸钠（DSS）水溶液,同时分别灌胃给予溶剂或干预药物（0.2ml/10g,1次/d×7d）。记录小鼠疾病活动指数（DAI）;测定结肠组织MDA含量,SOD、MPO活性及ICAM-1、NF-κBp65表达水平。结果模型组DAI显著增高,结肠黏膜损伤严重;MDA舍量、MPO活性及ICAM-1和NF-κBp65表达明显升高。SOD活性下降（P〈0.01）。SASP520mg/kg能明显逆转上述改变;ACAM100mg具有相似的作用。结论ACAM可能通过抗氧自由基作用,抑制炎性细胞活化、迁移及NF-κB激活,缓解小鼠结肠炎性反应。     

盐酸小檗碱对葡聚糖硫酸钠所致小鼠结肠炎的作用研究

目的研究盐酸小檗碱对小鼠实验性溃疡性结肠炎的保护作用。方法实验设正常、模型、柳氮磺胺吡啶(SASP,520 mg·kg-1)和盐酸小檗碱(berberine chloride,BER)低、中、高(15 mg·kg-1、45 mg·kg-1、150 mg·kg-1)剂量组。六组小鼠自由饮用4%葡聚糖硫酸钠(dextran sulphate sodium, DSS)水溶液或蒸馏水,同时分别灌胃给予干预药物或溶剂(0·2 mL / 10 gWt,1次/ d×7 d)。以疾病活动指数(Disease activity index, DAI)评价小鼠临床症状。生化方法测定结肠组织MDA含量,SOD、MPO活性;HE染色切片,评估结肠组织病理改变;免疫组化检测ICAM-1、NF-κB p65蛋白表达水平。结果模型组DAI显著增高,结肠黏膜损伤严重;MDA含量、MPO活性及ICAM-1和NF-κB p65表达明显升高,SOD活性下降。SASP 520 mg·kg-1能明显逆转上述情况改变;BER使DAI减小,结肠黏膜损伤减轻, MDA含量、MPO活性降低,阻遏ICAM-1和NF-κB p65蛋白表达,升高SOD活性,且呈现一定剂量依赖性。结论BER可能通过抗氧自由基作用,抑制ICAM-1表达及NF-κB激活,缓解DSS所致的小鼠结肠炎症。     

N-乙酰半胱氨酸对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎的保护作用

目的观察N-乙酰半胱氨酸(NAC)灌肠对小鼠急性溃疡性结肠炎的作用。方法5%葡聚糖硫酸钠(DSS)自由饮用7 d诱导小鼠急性溃疡性结肠炎,同时予以生理盐水(NS)、5-氨基水杨酸(5-ASA)、NAC保留灌肠,观察小鼠体重、粪便性状、隐血便血,计算疾病活动度(DAI)积分,检测结肠长度、结肠过氧化物酶(MPO)活性、血清过氧化物歧化酶(SOD)活力和丙二醛(MDA)含量及肠黏膜病理改变。结果NAC组小鼠隐血、便血、体重下降、DAI积分、病理改变等均好于模型组、NS组(P<0.05),与5-ASA组疗效相似。NAC组SOD活力高于模型组,MPO活性、MDA含量则低于模型组(P<0.05)。结论NAC对DSS诱导的小鼠急性溃疡性结肠炎黏膜损伤有保护作用,其机制可能与抗氧化应激有关。     

白花蛇舌草总黄酮防治小鼠溃疡性结肠炎的作用

目的:观察不同剂量白花蛇舌草总黄酮(FOD)对小鼠产生的溃疡性结肠炎(UC)的防治作用,并初步探讨其作用机制。方法:60只小鼠随机分为6组(n=10):正常对照组、模型组、柳氮磺胺吡啶(SASP)治疗组、FOD高、中、低剂量治疗组。正常对照组一直饮用纯化水,后5组自由饮用4%右旋葡聚糖硫酸钠(DSS)水溶液代替日常饮用水制备UC小鼠模型;造模同时,SASP治疗组灌胃SASP500mg.kg-1.d-1,FOD高、中、低剂量治疗组灌胃FOD分别为60,40,26.7mg.kg-1.d-1,正常对照组和模型组每天灌服等量生理盐水作对照。每天观察各组小鼠的临床症状,喂养7d后处死小鼠取结肠组织,观察结肠黏膜损伤情况,同时检测结肠组织中超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性、丙二醛(MDA)和一氧化氮(NO)含量。结果:与模型组比较,FOD高、中剂量治疗组症状不同程度的明显改善、结肠黏膜损伤减轻;结肠组织中SOD活性明显升高(P<0.05),MPO、MDA、NO活性或含量不同程度的明显降低(P<0.05);FOD高剂量治疗组与SASP治疗组作用相似。结论:FOD对小鼠UC作用显著,其机制可能与减少自由基...     

黎药益智仁不同极性部位提取物对实验性肠炎模型小鼠的影响

目的:考察黎药益智仁4种不同极性部位提取物对实验性肠炎模型小鼠的影响。方法:将益智仁70%乙醇提取物浸膏用水分散后,依次用石油醚、三氯甲烷、乙酸乙酯和正丁醇提取得相应部位提取物。将42只小鼠随机分为造模组(36只)和空白组(6只),造模组大鼠采用2,4,6-三硝基苯磺酸法复制实验性肠炎模型。成模后,将造模小鼠随机分为模型组、阳性组(柳氮磺胺吡啶肠溶片,52 g/kg)和益智仁不同极性部位(石油醚、三氯甲烷、乙酸乙酯和正丁醇部位)提取物组(剂量均为10 g/kg,以生药计),每组6只,ig给药,每天1次,连续9 d,给药体积为0.2 m L/10 g;空白组和模型组小鼠ig生理盐水。测定小鼠体质量变化,对疾病活动指数(DAI)进行评分,测定结肠组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、丙二醛(MDA)活性,观察结肠组织病理变化并进行评分。结果:与空白组比较,模型组小鼠体质量下降百分率、DAI评分以及结肠组织中MPO、MDA活性均显著升高(P<0.05或P<0.01),结肠组织发生明显病变。与模型组比较,各给药组小鼠体质量显著回升,DAI评分显著降低,MPO活性显著降低,病理评分显著降低;阳性组、益智仁正丁醇提取物和乙酸乙酯提取物组小鼠结肠组织中SOD活性显著升高,阳性组和益智仁乙酸乙酯提取物组小鼠结肠组织中MDA活性显著降低,差异均有统计学意义(P<0.05或P<0.01)。结论:益智仁4种极性部位提取物对实验性肠炎模型小鼠均有一定改善作用,其中以乙酸乙酯部位和正丁醇部位效果较好。     

枫蓼提取物对小鼠实验性溃疡性结肠炎的防治作用

目的探讨枫蓼提取物对小鼠溃疡性结肠炎的防治作用。方法通过小肠推进实验和番泻叶致小鼠腹泻模型观察小肠推进率、稀便率及腹泻指数。用4%葡聚糖硫酸钠(DSS)建立小鼠溃疡性结肠炎模型,对正常组、模型组、美沙拉嗪组、枫蓼提取物11.7,23.4和46.8 g·kg-1剂量组小鼠进行疾病活动指数(DAI)评分,测定结肠组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)和一氧化氮(NO)含量及髓过氧化物酶(MPO)的活性。结果枫蓼提取物46.8 g·kg-1能抑制小鼠小肠推进率,显著减少番泻叶致腹泻小鼠腹泻次数,降低腹泻率和腹泻指数(P<0.05)。结肠炎结果显示,与正常组比较,模型组小鼠体质量减轻,DAI评分增高(P<0.05),结肠组织中MPO活性、IL-1β、TNF-α、MDA和NO含量升高(P<0.01)。与模型组比较,枫蓼提取物46.8 g·kg-1组小鼠DAI评分降低29.1%(P<0.05);23.4和46.8 g·kg-1组结肠组织中MPO活性、TNF-α、MDA和NO含量均降低(P<0.05)。结论枫蓼提取物能改善DSS诱导小鼠溃疡性结肠炎,可能与解痉、止泻、抗炎、抗氧化及减少炎性介质释放等有关。     

芒果苷对实验性结肠炎小鼠的保护作用

目的 探讨芒果苷对小鼠实验性溃疡性结肠炎(ulcerative colitis,UC)的保护作用和机制.方法 将C57BL/6小鼠随机分为4组(n=10):正常对照组、模型组、柳氮磺胺吡啶组(SASP,350 mg·kg-1,腹腔注射)以及芒果苷组(MA,50 mg·kg-1,灌胃).除正常对照组外,其他组小鼠均以饮用水中添加葡聚糖硫酸钠(dextran sodium sulfate,DSS)造模.SASP组和MA组分别于造模前2 d每日给予SASP和MA直到实验结束.于造模7 d处死小鼠,对结肠行HE染色后进行组织损伤和炎性细胞浸润评分,以ELISA方法检测结肠黏膜髓过氧化物酶(MPO)活性和TNF-α水平.结果 模型组小鼠的病理损伤和评分、MPO活性和TNF-α水平均明显高于正常对照组,MA组上述指标比模型组明显改善,但改善效果不如SASP组明显.结论 芒果苷可以减轻实验性UC小鼠的结肠黏膜损伤,其UC保护作用机制可能与其抑制中性粒细胞浸润和减少炎症细胞因子产生有关.     

吲哚丙酸对葡聚糖硫酸钠诱导急性溃疡性结肠炎小鼠的影响

目的 研究吲哚丙酸(IPA)对葡聚糖硫酸钠(DSS)诱导急性溃疡性结肠炎(UC)小鼠的影响。方法将SPF级6～8周雄性C57BL/6小鼠随机分为对照组、DSS模型组(饮用3%DSS 7 d)及低、中、高剂量IPA组(在DSS给药前2 d行IPA灌胃),每组12只。每日观察小鼠的一般情况,根据体质量下降、大便性状和便血状况评定疾病活动指数(DAI); DSS给药第7日处死小鼠,测量结肠长度及评定病理学评分,ELISA检测各组小鼠血清髓过氧化物酶(MPO)及结肠组织MPO、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平。Western blot法检测各组小鼠结肠组织中核因子-κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)蛋白表达。结果 与对照组比较,DSS模型组DAI、结肠组织病理学评分、血清MPO及结肠组织TNF-α、IL-1β、IL-6、MPO和p-NF-κB p65/NF-κB p65比值显著升高,结肠长度明显缩短(P <0.05,P <0.01);与DSS模型组比较,中、高剂量IPA...     

环孢素A对DSS结肠炎小鼠肠黏膜通透性影响及其机制的研究

目的探讨环孢素A(CsA)对葡聚糖硫酸钠(DSS)结肠炎小鼠肠黏膜通透性的影响及作用机制。方法 C57BL/6J小鼠(6～8周龄、体质量20 g±2 g、♂),实验分为正常对照组(饮用无菌蒸馏水+腹腔注射0.9%NS)、DSS模型组(DSS溶液+腹腔注射0.9%NS)、环孢素A组(DSS溶液+腹腔注射CsA)。小鼠自由饮用5%DSS溶液1周制备结肠炎模型,环孢素A(0.025 mg.g-1)腹腔注射给药,每天1次,共7 d。每日行DAI评分,实验结束后取结肠进行HE染色评分,结肠匀浆检测MPO活性、TNF-α、IFN-γ、IL-13和IL-17水平,另取小鼠小肠黏膜进行透射电镜检查和肌球蛋白轻链激酶(MLCK)活性测定,采用Evans blue和异硫氰酸荧光素-葡聚糖(FITC-D)方法检测小肠黏膜通透性。结果与正常对照组比较,模型对照组小鼠1周后出现明显体重减轻、便血和腹泻,DAI评分和HI评分增高,同时结肠黏膜MPO活性明显增高。电镜检查小鼠回肠黏膜上皮绒毛萎缩、排列不规则,细胞间连接复合体缩短、变宽,细胞间隙扩大,小肠黏膜通透性增高。小鼠结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度增高,小肠黏膜中MLCK活性明显增高。与DSS模型组比较,环孢素A组小鼠DAI评分和HI评分明显降低,结肠黏膜MPO活性减低,回肠黏膜上皮细胞绒毛排列整齐,小肠黏膜通透性降低,小肠黏膜MLCK活性和结肠匀浆中TNF-α、IFN-γ、IL-13和IL-17水平均有不同程度降低。结论环孢素A具有明显的抗DSS小鼠结肠炎作用,机制可能与通过调控MLCK表达,改善肠黏膜通透性有关。     

泻痢消片治疗实验性结肠炎的研究

目的考察泻痢消片对大鼠实验性结肠炎的保护作用。方法雄性SD大鼠随机分为6组,每组10只。除空白对照组外,其他组用2,4-二硝基氯苯和醋酸灌肠的方法制备大鼠结肠炎模型。泻痢消高、中、低剂量组分别给予泻痢消溶液0.28,0.56,1.12 g.kg-1,阳性对照组给予柳氮磺吡啶(0.27 g.kg-1),造模次日开始给药,每天1次,连续14 d。对大鼠疾病活动指数(DAI)进行评分,测定结肠组织中核因子κBp65(NF-κBp65)表达和髓过氧化物酶(MPO)水平。结果泻痢消高、中、低剂量组能够降低大鼠DAI评分,降低结肠组织中NF-κBp65表达和MPO水平(P<0.05或P<0.01)。结论泻痢消可以减轻肠道炎症,对实验性结肠炎有良好疗效。     

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

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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。     

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     

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.     

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.