p38 MAPK-IN-1_1006378-90-0_DataSheet_MedChemExpress
气道炎症中p38MAPK及核因子κB对一氧化氮合酶的调控
气道炎症中p38MAPK及核因子κB对一氧化氮合酶的调控田伟千，傅诚章，朱敏敏（南京医科大学第一附属医院麻醉科，江苏南京210029）[摘要] 气道炎症性疾病是由多种细胞因子、炎性介质介导的变态反应性疾病，一氧化氮（NO）作为生物体内一个重要的信使分子和效应分子,参与许多生理和病理过程，大量的NO可引起气道炎症和肺损伤等不良反应。
p38蛋白激酶(p38 MAPK)可能与气道炎症性疾病的发病机制密切相关，且能调控诱导型一氧化氮合酶（iNOS）mRNA 的表达及NO 的产生。
同时，p38MAPK 还是NF-κB的重要上游调控因子。
作为一种多极性基因调控蛋白, 核因子κB(NF-κB)能从基因转录水平调控iNOS的合成,因而对NO具有重要的调节作用。
NO对p38MAPK和NF-κB也有一定的反馈调节作用。
[关键词] 气道炎症；p38MAPK；NF-κB；诱导型一氧化氮合酶；一氧化氮P38 Mitogen activated Protein Kinase and Nuclear Factor-κB Modulate the inducible Nitric oxide Synthase in airway inflammationTian Weiqian , Fu Chengzhang, Zhu Minmin . Department of Anesthesiology ,the First Affiliated Hospital of Nanjing Medical University , Nanjing 210029 CHINA[Abstract]Airway inflammatory disease is characterized by allergic airway inflammation,which is mediated by various cytokines and inflammatory mediators. As an important signaling and potent molecule, NO is involved in numerouspathophysiological processes in creature bodies. Excessive production of endogenous NO in airway inflammatory disease may contribute to many adverse responses ,such as airway inflammation and lung injury etc. P38 Mitogen activated Protein Kinase ,which is likely to correlate closely with the pathogenesis of airway inflammatory disease,could Modulate iNOS mRNA expression and NO production, and p38MAPK is also an important upstream regulating factor. As a multipolar gene modulin,NF-κB can modulate the biosynthesis of inducible nitric oxide synthase at the level of nuclear transcription,thereby it is a critical factor in regulating NO production.However, No also shows a feedback regulation effect on p38MAPK and NF-κB.[Key words] airway inflammation; P38 mitogen activated protein kinase; nuclear factor-κB; inducible nitric oxide synthase; nitric oxide一氧化氮(NO) 是一种活跃的信号小分子,参与机体多种生理和病理过程。
p38MAPK在糖尿病心肌病中的作用研究进展
p38MAPK在糖尿病心肌病中的作用研究进展p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase，p38MAPK）是丝裂原活化蛋白激酶（MAPK）信号系统的重要分支，是主要分布于细胞浆的一种丝氨酸/苏氨酸蛋白激酶，它在糖尿病心肌病（diabetic cardiomyopathy，DCM）发病中起重要作用，可被多种因素激活，在微血管病变、心肌间质纤维化、心肌肥厚、心肌凋亡中扮演着重要角色。
深入研究p38MAPK在DCM中的分子机制，有助于阐明DCM发病机制，为防治DCM提供新靶点。
糖尿病心肌病（diabetic cardiomyopathy，DCM）是独立于冠心病、高血压等的特异性心肌病，可诱发心力衰竭、心律失常、心源性休克和猝死，已成为糖尿病患者的主要死因。
病理表现为心肌肥厚、弥漫性心肌壁内微血管病变，毛细血管密度降低、内皮及内皮下纤维增生和基膜增厚。
其发病机制复杂，涉及心肌细胞代谢障碍、心肌微血管病变、心肌纤维化、自主神经病变、胰岛素抵抗及炎症因子等多个方面。
近年研究发现p38MAPK在DCM的发生发展中占有重要的地位，它参与血管活性物质和细胞因子的产生，引起细胞生长、增殖和分化，是DCM发病的重要信号通路。
本文就p38MAPK在糖尿病心肌病中的作用作一综述。
1 p38MAPK的结构与调节机制p38MAPK是1993年Brewster等[1]发现，由360个氨基酸组成的38KD的蛋白，与细胞外信号调节激酶1/2（extracellular-signal regulated kinase，ERK1/2）、c-Jun氨基末端激酶（c-Jun N-terminal kinase，JNK）一起构成MAPK系统信号系统的3个主要分支。
MAPK是丝氨酸/苏氨酸蛋白激酶，可由活性氧应激性刺激激活，另外可以通过与生长因子受体及G蛋白偶联受体结合而激活。
p38MAPK 有6种异构形式，分别为p38MAPK α1/α2、p38MAPK β1/β2、p38γMAPK和p38δMAPK，不同亚型的分布具有组织特异性，p38α、p38β广泛分布于各种组织，p38γ主要分布于骨骼肌，p38δ主要分布于腺体组织，其中p38α和p38γ是心脏表达较多的亚型[2-3]。
P38MAPK在低氧及炎症联合刺激诱导人肺微血管内皮细胞凋亡中的作用
P38MAPK在低氧及炎症联合刺激诱导人肺微血管内皮细胞凋亡中的作用吉圣珺;魏晓群;莫冠文;梅湛强;张培芳【期刊名称】《中国循证心血管医学杂志》【年(卷),期】2016(008)006【摘要】Objective To investigate the effect of p38mitogen-actvated protein kinase (P38MAPK) on the apoptosis of human pulmonary microvascular endothelial cells induced by hypoxia and inflammation.Methods Human pulmonary microvascular endothelial cell line was recovered, subcultured, divided into blank control group, hypoxia group (hypoxia 6 h, 12 h, 24 h) and TNF alpha stimulation group (10 ng/ml, 20 ng/ml, 50 ng/ml, 100 ng/ml TNF alpha), model group (hypoxia combined with 100 ng/ml TNF alpha ) and pathway blocker group(SB203580). P38MAPK expression in each group was detected by Western blotting. Caspase-3 activity in each group was analyzed by flow cytometry. Apoptosis were detected by combination of flow cytometry and TUNEL assay.Results Compared with the blank control group, p-P38MAPK expression of model group was increased (P<0.05). Caspase-3 activity of model group (24 h hypoxia combined with 100ng/ml TNF alpha) was reduced compared with hypoxia group (24 h) and TNF alpha stimulation group (100 ng/ml) (P<0.01); Caspase-3 activity of pathway blocker group was reduced compared with model group (P<0.01). Apoptosis rate andapoptotic index were reduced in pathway blocker group than model group (P<0.01).Conclusion P38MAPK plays a role in promoting in human pulmonary microvascular endothelial cells apoptosis induced by hypoxia and inflammation. P38MAPK pathway blocker (SB203580) has protective effect on hypoxia and inflammation in human pulmonary microvascular endothelial cells.%目的：探讨P38MAPK在低氧及炎症联合刺激诱导人肺微血管内皮细胞凋亡中的作用。
p38MAPK在糖尿病心肌病中的作用研究进展
p38MAPK在糖尿病心肌病中的作用研究进展揭海;吴铿【期刊名称】《中国医学创新》【年(卷),期】2015(12)13【摘要】p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase，p38MAPK）是丝裂原活化蛋白激酶（MAPK）信号系统的重要分支，是主要分布于细胞浆的一种丝氨酸/苏氨酸蛋白激酶，它在糖尿病心肌病（diabetic cardiomyopathy，DCM）发病中起重要作用，可被多种因素激活，在微血管病变、心肌间质纤维化、心肌肥厚、心肌凋亡中扮演着重要角色。
深入研究p38MAPK在DCM中的分子机制，有助于阐明DCM发病机制，为防治DCM提供新靶点。
%p38 mitogen-activated protein kinase(p38MAPK)is an important member of the mitogen-activated proteinkinase(MAPK)superfamily,which is mainly distributed in the cytoplasm and a serine/threonine kinase. It plays an important role in the pathogenesis of diabetic cardiomyopathy(DCM),such as microvascular disease,myocardial fibrosis,cardiac hypertrophy,myocardial apoptosis and so on,which can be activated by a variety of factors. Studying the role of p38MAPK is helpful to further clarify the pathogenesis of DCM,as well as to provide new target for DCM treatment.【总页数】4页(P153-156)【作者】揭海;吴铿【作者单位】广东医学院附属医院广东湛江 524001;广东医学院附属医院广东湛江 524001【正文语种】中文【相关文献】1.泛素连接酶Cbl－b调控p38MAPK在胰岛素与硒协同抑制糖尿病心肌病大鼠心肌细胞凋亡中的作用 [J], 徐天娇;刘勇;李萍;胥晓丽;曾菊绒2.p38MAPK在糖尿病肾脏疾病中的作用研究进展 [J], 沈霞蔚;邓德明;孙爱萍3.P38mAPK信号通路在糖尿病肾病中的作用 [J], 郭娟娟;陈莉明4.胰岛素在糖尿病性心肌病发病中作用的研究进展 [J], 丘如5.AMPK在糖尿病缺血性心肌病中的作用研究进展 [J], 李泳洁;王江因版权原因，仅展示原文概要，查看原文内容请购买。
P38 MAPK INHIBITORS FOR THE TREATMENT OF INFLAMMAT
专利名称：P38 MAPK INHIBITORS FOR THETREATMENT OF INFLAMMATORY DISEASES 发明人：Patricia Gómez,Esther Carrasco,PedroCampos,Patricia Deleyto,Miguel Vega,JuanJesús Gómez-Reino,Carmen Conde,OresteGualillo,Juan Jesús Pérez,Ángel Messeguer 申请号：US14902726申请日：20121217公开号：US20160194336A1公开日：20160707专利内容由知识产权出版社提供摘要：The present invention provides new p38 mitogen activated protein (MAP) kinase allosteric inhibitors which are useful for the treatment of p38 mediated diseases such as inflammatory diseases, e.g. rheumatoid arthritis, osteoarthritis, psoriatic arthritis, pain, musculoskeletal system inflammation and musculoskeletal system aging. The present invention thus provides compounds for use in a method for treatment of inflammatory diseases, as well as for use in therapy in general, wherein the compound binds to the region composed of amino acids at positions 170-199 of Mitogen-activated protein kinase 14 (Uniprot accession nr Q16539 or SEQ ID No 1) and/or Mitogen-activated protein kinase 11 (Uniprot accession nr Q15759 or SEQ ID No 2), SEQ ID NO. 1 and SEQ ID NO. 2 being the amino acid sequences of MAPK14 (p38cx) and MAPK11 (p38β), respectively. The specific region composed of amino acids at positions 170-199 is herein disclosed as SEQ ID NO. 4 for Mitogen-activated protein kinase 14 and SEQ ID NO. 5 for Mitogen-activated protein kinase 11 and are believed to be new inhibitory binding sites.申请人：ALLINKY BIOPHARMA 地址：Madrid ES国籍：ES更多信息请下载全文后查看。
SB203580_p38MAPK抑制剂_说明书
SB203580_p38MAPK抑制剂_说明书SB203580 (p38 MAPK抑制剂)产品简介：SB203580也写作SB 203580或SB-203580，是一种常用的p38 MAPK抑制剂。
SB203580可以通透细胞，抑制p38 MAPK (p38 MAP kinase)，抑制后续MAPKAP Kinase-2和MAPKAP Kinase-3的激活。
通过抑制p38 MAPK，SB203580可以有效抑制一些炎症因子(如IL-1β、TNF-α)诱导的部分信号转导。
SB203580选择性抑制p38 MAPK，IC50为600 n M；对于JNK/SAPK和p44/42 MAPK (即Erk1/2)无显著的抑制作用，IC50仅为100 μM。
SB203580分子量为377.43，分子式为C21H16N3FOS，CAS Number：152121-47-6。
本产品纯度大于99%。
本SB203580为进口分装，用DMSO配制，浓度为20mg/ml，共50μl。
保存条件：-20℃避光保存，一年有效。
注意事项：SB203580对人体有刺激性，请注意适当防护。
本SB203580在4℃、冰浴等较低温度情况下会凝固而粘在离心管管底、管壁或管盖内，可以20-25℃水浴温育片刻至全部融解后使用。
为了您的安全和健康，请穿实验服并戴一次性手套操作。
使用说明：1.SB203580常见使用浓度范围为1-50μM。
具体的最佳工作浓度请参考相关文献，或根据实验目的，以及所培养的特定细胞和组织，通过实验进行摸索和优化。
使用本产品的文献：1. Shi X, Zhou B.The role of Nrf2 and MAPK pathways in PFOS-induced oxidative stress in zebrafish embryos.Toxicol Sci. 2010;115(2):391-400. Epub 2010 Mar 3.2. Jiang Z, Li S, Liu Y, Deng P, Huang J, He G.Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinaseup-regulation via cAMP signaling pathway.Acta Biochim Biophys Sin (Shanghai). 2011 Oct;43(10):763-70.3. Jin W, Li Q, Lin Y, Lu Y, Li H, Wang L, Hu R, Ma L, Wang J, Pang T.Reversal of Imatinib resistance in BCR-ABL-positive leukemia after inhibition of the Na+/H+exchanger.Cancer Lett. 2011 Sep 1;308(1):81-90.4. Gong J, Shen XH, Chen C, Qiu H, Yang RG.Down-regulation of HIV-1 infection by inhibition of the MAPK signaling pathway.Virol Sin. 2011 Apr;26(2):114-22.5. Lin M, Wang X, Zhu J, Fan D, Zhang Y, Zhang J, Guo Z.Cellular and biomolecular responses of human ovarian cancer cells to cytostatic dinuclearplatinum(II) complexes.Apoptosis. 2011 Mar;16(3):288-300.6. Fang S, Jin Y, Zheng H, Yan J, Cui Y, Bi H, Jia H, Zhang H, Wang Y, Na L, Gao X, Zhou H.High glucose condition upregulated Txnip expression level in rat mesangial cells throughROS/MEK/MAPK pathway.Mol Cell Biochem. 2011 Jan;347(1-2):175-82.7. Li W, Liu Y, Li XX, Yu Y, Wu JJ, Wang Q, Huo H, Wang LM, Yang L.MAPKs are not involved in triptolide-induced cell growth inhibition and apoptosis in prostate cancer cell lines with different p53 status.Planta Med. 2011 Jan;77(1):27-31.8. Feng J, Zhang P, Chen X, He G.PI3K and ERK/Nrf2 pathways are involved in oleanolic acid-induced heme oxygenase-1 expressionin rat vascular smooth muscle cells.J Cell Biochem. 2011 Jun;112(6):1524-31.9. Sun C, Wang L, Yan J, Liu S.Calcium ameliorates obesity induced by high-fat diet and its potential correlation with p38 MAPKpathway.Mol Biol Rep. 2012 Feb;39(2):1755-63.10.Zhu F, Shen F, Fan Y, Xie Y, Xia Y, Kong YOsteopontin increases the expression of β1, 4-Galactosyltransferase-I and promotes adhesion inhuman RL95-2 cells.Glycoconj J. 2012 Jul 31.11.Wang LH, Chang GQ, Zhang HJ, Wang J, Lin YN, Jin WN, Li HW, Gao W, Wang RJ, Li QH, Pang TX.Neutrophil gelatinase-associated lipocalin regulates intracellular accumulation of Rh123 in cancercells.Genes Cells. 2012 Mar;17(3):205-17.12.Guo C, Yuan H, He Z.Melamine causes apoptosis of rat kidney epithelial cell line (NRK-52e cells) via excessiveintracellular ROS (reactive oxygen species) and the activation of p38 MAPK pathway.Cell Biol Int. 2012 Apr 1;36(4):383-9.13.Sun C, Qi R, Wang L, Yan J, Wang Yp38 MAPK regulates calcium signal-mediated lipid accumulation through changing VDRexpression in primary preadipocytes of mice.Mol Biol Rep. 2012 Mar;39(3):3179-84.14.Teng M, Jiang XP, Zhang Q, Zhang JP, Zhang DX, Liang GP, Huang YS.Microtubular stability affects pVHL-mediated regulation of HIF-1alpha via the p38/MAPK pathway inhypoxic cardiomyocytes.PLoS One. 2012;7(4):e35017.15.Zhong Y, Liu T, Guo Z.Curcumin inhibits ox-LDL-induced MCP-1 expression by suppressing the p38MAPK and NF-κBpathways in rat vascular smooth muscle cells.Inflamm Res. 2012 Jan;61(1):61-7.。
P38 MAPK在大鼠体外循环肺组织炎症反应中的作用
P38 MAPK在大鼠体外循环肺组织炎症反应中的作用董啸;徐建军;何雄【期刊名称】《山东医药》【年(卷),期】2008(48)27【摘要】54只SD大鼠随机分为3组,全麻开胸组(S组)、体外循环组(CPB组)、体外循环+P38 MAPK阻断剂组(SB组).Western blot法检测大鼠肺组织中P38 MAPK、磷酸化P38 MAPK,EMSA法检测激活蛋白(AP-1)的DNA结合活性变化,ELISA法检测TNF-α和IL-1β产量,并留取肺组织做HE染色病理检查.发现在磷酸化P38 MAPK、AP-1、TNF-α、IL-1β方面,CPB组较S组明显增高,SB组较CPB组明显减少.认为P38 MAPK通过影响AP-1的激活而参与体外循环术后肺炎症反应的发生,SB203580通过阻断P38 MAPK的激活而减轻体外循环术后肺炎症反应的发生.【总页数】3页(P45-47)【作者】董啸;徐建军;何雄【作者单位】南昌大学第二附属医院,江苏南昌,330006;南昌大学第二附属医院,江苏南昌,330006;南昌大学第二附属医院,江苏南昌,330006【正文语种】中文【中图分类】R563.1【相关文献】1.右美托咪啶对大鼠肺IRI中p38MAPK信号通路及肺组织HMGB1表达的影响[J], 王晓光;齐晓非;李戈辉2.大黄素对肺炎链球菌肺炎小鼠肺组织炎症反应及p38 MAPK表达的影响 [J], 谢璟;王荣丽3.肝脏p38MAPK/NF-κB通路在大鼠烧伤休克期切痂以减轻炎症反应中的作用 [J], 段建兴;刘文军;曾跃勤;张高飞;王迪;李佳美;娄涵潇4.大鼠骨骼肌挫伤修复过程中p38 MAPK通路、炎症反应的作用 [J], 王屿萌;廖苾芝;周达岸5.丹芍化纤胶囊对肺纤维化大鼠肺组织中calpain2,NF-κB及p38MAPK表达的影响 [J], 谢汝佳;韩冰;何小飞;杨婷;杨勤因版权原因，仅展示原文概要，查看原文内容请购买。
p38-MAPK-IN-1-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-01-2018Print Date:Oct.-01-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :p38 MAPK-IN-1Catalog No. :HY-12839CAS No. :1006378-90-01.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:NoneFormula:C21H15F2N2OMolecular Weight:349.35CAS No. :1006378-90-04. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance Light yellow to yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. 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p38促分裂素活化激酶(MAPK)是马中性粒细胞趋化游走的关键
p38促分裂素活化激酶(MAPK)是马中性粒细胞趋化游走的关键Rachael;宋筱瑜【期刊名称】《中国畜牧兽医》【年(卷),期】2009(0)6【摘要】马的足板层组织正常并不含有中性粒细胞,且与马的其他组织相比含有非常少量的超氧化物歧化酶,因此该组织易受到进入其中的中性粒细胞所产生的反应性氧族侵袭。
在急性足板层炎临床进展期,感染足部的病理学变化包括基底膜的破坏,中性粒细胞的浸润,以及足板层静脉血小板-中性粒细胞的积聚,使得中性粒细胞对于该病的病生理发展变得尤为明显。
本研究的目的是揭示p38促分裂素活化激酶(MAPK)在马粒细胞趋化游走中的作用,从而找到治疗靶点,并可减少急性足板层炎时中性粒细胞进入导致的足板层损伤。
研究发现内源性的化学趋化物LTB4能短暂激活p38 MAPK,并能诱导马中性粒细胞的趋化。
使用p38MAPK特异性抑制剂SB203580可减少LTB4诱导的趋化游走并呈剂量相关性,其中半数有效浓度为2.8 mmol/L。
然后研究了SB203580能减少趋化游走的可能机制。
研究发现使用10 mmol/L SB203580抑制p38 MAPK可破坏中性粒细胞受LTB4和PAF刺激后的极化分裂能力。
相比而言,p38 MAPK在化学趋化物或PKC诱导的β2整合素依赖性吸附或化学趋化物诱导上调表达表面β2整合素中并不是必需的,但对于TNFα诱导的吸附是必需的。
这些发现证实了p38 MAPK在马中性粒细胞趋化游走中的功能,表明抑制p38 MAPK可减少急性足板层炎时马足板层中性粒细胞炎性反应的发生。
【总页数】1页(P26-26)【关键词】其它动物;炎性反应;足板层炎【作者】Rachael;宋筱瑜【作者单位】【正文语种】中文【中图分类】Q959.837;Q26【相关文献】1.p38丝裂素活化蛋白激酶抑制剂Dilmapimod（度马莫得）用于防治严重创伤合并急性呼吸窘迫综合征患者的安全性：一项Ⅱ期剂量递增试验结果分析 [J], 罗红敏2.高糖环境下趋化素与其受体ChemR23通过活化p38 MAPK促进肾小球内皮细胞炎性因子IL-6、TNF-α的表达 [J], 张晓雪;王璐瑶;尚进;宁丽娜;赵继芳;窦艳娜;郭佳;肖静;赵占正3.p38丝裂素活化蛋白激酶信号通路在单核细胞趋化蛋白1介导系膜细胞增殖及细胞外基质表达中的作用 [J], 周文祥;刘晓城;张俊;韩敏4.高压氧对大鼠早期脓毒症膈肌p38促分裂素原活化蛋白激酶信号通路的影响 [J], 李厚成;罗杰;刘培;李彬彬;刘玉;吴建平;宁红平5.紫草素对肺炎链球菌引起的肺炎小鼠细胞外信号调节激酶/p38丝裂素活化蛋白激酶/核苷酸结合寡聚化结构域样蛋白3信号通路及肺血管通透性的影响 [J], 卫丽;刘虹;闫鲜鹏因版权原因，仅展示原文概要，查看原文内容请购买。
P38 MAPK抑制剂的计算机辅助药物研究的开题报告
P38 MAPK抑制剂的计算机辅助药物研究的开题报
告
题目：P38 MAPK抑制剂的计算机辅助药物研究
研究背景：
P38 MAPK是一种丝裂原活化蛋白激酶，在各种生理和病理过程中都发挥重要作用。
该蛋白激酶的异常信号通路与许多疾病相关，例如炎症、肿瘤、心血管疾病、糖尿病等。
因此，开发P38 MAPK抑制剂对于治疗这些疾病具有重要意义。
计算机辅助药物研究已经成为新药开发的重要参考工具，通过计算
机模拟药物和靶点之间的相互作用，可以快速预测药物的活性、毒性、
代谢等特性，并辅助优化药物设计。
研究目的：
本研究旨在通过计算机辅助药物研究方法，筛选出具有良好P38 MAPK抑制活性的化合物，并对其进行药物设计和优化，以期为P38 MAPK相关疾病的治疗提供有效的药物。
研究方法：
1.构建靶点P38 MAPK的三维结构模型；
2.建立化合物数据库，并进行性能分析和ADME预测；
3.通过分子对接、分子动力学模拟等计算机手段，评估化合物与P38 MAPK之间的相互作用；
4.根据计算结果，进行药物设计和结构优化；
5.最终通过生物学实验验证筛选出的化合物的抑制活性和毒性。
研究意义：
该研究将通过计算机辅助药物研究方法，筛选并优化具有良好活性的P38 MAPK抑制剂，为炎症、肿瘤、心血管疾病、糖尿病等相关疾病药物开发提供新思路和方法，并为新药研发提供参考和帮助。