灵芝孢子对支气管哮喘豚鼠引喘潜伏期及类胰蛋白酶释放的影响

目的研究灵芝孢子对支气管哮喘（简称哮喘）豚鼠引喘潜伏期及肥大细胞类胰蛋白释放的影响。方法10％卵蛋白腹腔注射致敏,雾化吸入1％卵蛋白方式诱导复制哮喘动物模型。30只健康豚鼠随机分为对照组（A）、哮喘组（B）、灵芝组（C）3组,每组10只,分别用生理盐水,灵芝孢子灌胃15d。测定哮喘豚鼠的引喘潜伏期及呼气相气道阻力（Re）,计数支气管肺泡灌洗液（BALF）细胞总数及分类,肺组织HE染色和免疫组织化学观察肺组织病理变化及肥大细胞类胰蛋白酶分布情况。结果①灵芝组的引喘潜伏期明显较哮喘模型组延长,Re显著降低（P〈0．05）。②哮喘BALF白细胞总数及嗜酸粒细胞比例较生理盐水组增高（P〈0．05）,肺组织炎性病变明显;灵芝组BALF细胞总数、嗜酸粒细胞比例及肺组织炎性病变明显较哮喘组降低或减轻（P〈0．05）。③哮喘组类胰蛋白酶染色阳性的肥大细胞计数明显较生理盐水组增多（P〈0．05）,主要分布在气道黏膜下,肺泡间隔及血管周围;灵芝组类胰蛋白酶染色阳性的肥大细胞计数较哮喘组显著减少。结论灵芝孢子有延长哮喘豚鼠引喘潜伏期,降低气道阻力,减轻肺组织炎性病变,抑制肥大细胞释放类胰蛋白酶的作用。     

灵芝孢子对支气管哮喘豚鼠引喘潜伏期及类胰蛋白酶释放的影响

目的 研究灵芝孢子对支气管哮喘(简称哮喘)豚鼠引喘潜伏期及肥大细胞类胰蛋白释放的影响.方法 10%卵蛋白腹腔注射致敏,雾化吸入1%卵蛋白方式诱导复制哮喘动物模型.30只健康豚鼠随机分为对照组(A)、哮喘组(B)、灵芝组(C)3组,每组10只,分别用生理盐水,灵芝孢子灌胃15 d.测定哮喘豚鼠的引喘潜伏期及呼气相气道阻力(Re),计数支气管肺泡灌洗液(BALF)细胞总数及分类,肺组织HE染色和免疫组织化学观察肺组织病理变化及肥大细胞类胰蛋白酶分布情况.结果 ①灵芝组的引喘潜伏期明显较哮喘模型组延长,Re显著降低(P＜0.05).②哮喘BALF白细胞总数及嗜酸粒细胞比例较生理盐水组增高(P＜0.05),肺组织炎性病变明显;灵芝组BALF细胞总数、嗜酸粒细胞比例及肺组织炎性病变明显较哮喘组降低或减轻(P＜0.05).③哮喘组类胰蛋白酶染色阳性的肥大细胞计数明显较生理盐水组增多(P＜0.05),主要分布在气道黏膜下,肺泡间隔及血管周围;灵芝组类胰蛋白酶染色阳性的肥大细胞计数较哮喘组显著减少.结论 灵芝孢子有延长哮喘豚鼠引喘潜伏期,降低气道阻力,减轻肺组织炎性病变,抑制肥大细胞释放类胰蛋白酶的作用.     

银杏内酯A通过p38MAPK通路减轻中性粒细胞性哮喘小鼠气道炎症

目的探索银杏内酯A(Ginkgolide A,GA)对中性粒细胞为主的哮喘小鼠气道炎症的影响及可能的机制。方法28只雌性BALB/c小鼠随机分为对照组、哮喘组、GA干预组、地塞米松(dexamethasone,DEX)干预组,每组7只。哮喘组于第0、14、21天给予20ug卵清蛋白(ovalbumin,OVA)+75ul氟氏制剂(complete Freund’s adjuvant,CFA)腹腔注射致敏,第22-24天连续3天5%OVA雾化激发,对照组给予PBS致敏与激发。GA干预组及DEX干预组分别在每次激发前1小时给予80mg/kg GA及1mg/kg DEX腹腔注射。末次激发24小时后,对各组小鼠进行肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中细胞总数及细胞分类计数,检测BALF中超氧化物歧化酶(superoxide dismutase,SOD)水平、肺组织中p-ERK、p-p38、p-p85的蛋白水平,并对各组小鼠肺组织病理学特征进行评价。结果与对照组比较,哮喘组小鼠BALF中细胞总数及中性粒细胞计数均明显增加、SOD水平明显下降,气道粘液分泌及周围炎症细胞聚集明显加重,肺组织中p-p38蛋白表达水平明显升高,差异具有统计学意义(P<0.05)。经银杏内酯A干预后,哮喘小鼠BALF中细胞总数及中性粒细胞计数明显减少、气道粘液分泌及气道周围炎症细胞聚集明显减轻,BALF中SOD水平明显升高,同时肺组织中p-p38的表达水平明显下降,差异具有统计学意义(P<0.05)。经地塞米松干预组,上述指标变化不明显(P>0.05)。结论银杏内酯A可减轻中性粒细胞为主的哮喘小鼠气道周围炎症及氧化应激过程,其作用机制与p38丝裂原激活蛋白激酶(p38 Mitogen-activated protein kinase,p38MAPK)通路有关,可作为中性粒细胞为主的哮喘的有效治疗药物。     

异氟醚吸入对新生大鼠认知功能的影响及p38MAPK抑制剂的干预作用

目的探讨p38细胞内丝裂原活化蛋白激酶通路（MAPK）通路在异氟醚诱发新生大鼠认知功能障碍中的作用。方法将60只7日龄SD大鼠随机分为5组各12只。其中A组正常饲养;B、C组均置于自制麻醉气体吸入箱中并分别吸入1.2%、1.8%异氟醚,D、E组处理分别同B、C组,但在吸入异氟醚前30 min腹腔注射p38MAPK抑制剂SB203580。6周后各组均进行行为学实验观察逃逸潜伏期（T1）、空间探索时间（T2）,并取海马组织采用Western blot法测定p38蛋白含量。结果 B、C组T1均显著长于A组,而D、E组分别显著短于B、C组（P均〈0.05）;B、C组T2均显著短于A组,而D、E组分别显著长于B、C组;B、C组海马区p38蛋白含量显著高于A组,而D、E组分别显著低于B、C组（P均〈0.05）。结论异氟醚诱发新生大鼠认知功能障碍与p38MAPK通路活化有密切关系,抑制该通路活化可减轻认知功能损害。     

哮喘小鼠模型的建立与评价

目的探讨哮喘小鼠模型建立的方法。方法将20只SPF级BALB／C雌性小鼠随机分成对照组和模型组两组。模型的构建采用腹腔注射OVA＋氢氧化铝凝胶致敏3次后予1％OVA雾化激发7d,以生理盐水腹腔注射及雾化吸人为对照。最后1次雾化激发1h后眼球取血,取右肺作HE染色;左肺收集BALF,进行细胞计数;ELISA检测外周血IL—12水平。结果模型组小鼠激发可见典型的哮喘症状。模型组小鼠BALF中炎性细胞总数和EOS较对照组明显增多,外周血IL-12水平显著降低,且IL-12水平与BALF中EOS数呈高度负相关。结论致敏3次后雾化激发是一种较好的建立哮喘小鼠模型的方法。     

姜黄素通过p38MAPK/NF-κB信号通路抑制哮喘大鼠气道炎症的实验研究

目的探究姜黄素对哮喘模型大鼠肺组织中NF-κBp65与p38MAPK表达的影响。方法 4-5周龄40只清洁级雌性SD大鼠,将分为以下四组:Control组(正常对照组)、哮喘模型组(OVA致敏)、姜黄素低剂量组(OVA致敏+姜黄素100mg/kg)和姜黄素高剂量组(OVA致敏+姜黄素200mg/kg),每组10只。将支气管肺泡灌洗液(BALF)内细胞行Diff-quik染色后计算细胞总数和各分组的细胞数;左肺组织切片进行HE病理学染色观察其炎症细胞的变化;运用酶联免疫吸附法(ELISA)联合蛋白质印迹(Western blot,WB)法并结合免疫组织化学法对过敏性炎症介质进行初步评估,并且检测肺组织细胞核中NF-κBp65、磷酸化p38MAPK(p-p38 MAPK)的表达及致炎因子如白介素-5(IL-5)、白介素-13(IL-13)及干扰素-γ(IFN-γ)含量的变化。结果 CUR1组与CUR2组大鼠BALF中多种炎性细胞数、IL-4、IL-5、IFN-γ含量以及NF-κBp65核转位与磷酸化MAPK水平明显降低,浸润的炎性细胞计数减少,肺组织病理学改变较哮喘模型组显著减轻,差异具有统计学意义(P0.01)。。结论姜黄素能抑制p38MAPK、NF-κBp65和阻断IL-5、IL-13炎症因子,且与减轻肺组织炎性细胞浸润有密切的关系。     

TGF⁃β1 p38MAPK及BMP⁃7蛋白在肝多房棘球蚴病患者肝组织中的表达及意义

目的　检测肝多房棘球蚴病患者肝组织中转化生长因子⁃β1（transforming growth factor⁃β1, TGF⁃β1）、p38MAPK及骨形态发生蛋白⁃7（bone morphogenetic protein⁃7, BMP⁃7）表达水平,探讨其在肝多房棘球蚴病肝纤维化中的潜在作用。方法　以20例肝多房棘球蚴病患者为研究对象,分别采集距肝脏病灶0.5 cm内（A组）、距肝脏病灶0.5～1.5 cm（B组）肝组织及距肝脏病灶2 cm及以上的正常肝组织（C组）。肝组织标本分别行HE和Masson染色观察纤维化病理变化,采用Western blotting检测肝组织中TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平,分析TGF⁃β1、p38MAPK及BMP⁃7蛋白表达与肝纤维化的相关性。结果　HE染色结果显示,A组和B组肝组织中肝细胞结构排列紊乱、肝小叶结构有不同程度破坏,可见不同程度肝细胞变性、萎缩、坏死及纤维组织增生,并有嗜酸性粒细胞浸润;C组肝组织无异常病理改变,肝细胞结构形态正常、大小均匀,未见明显排列紊乱,肝小叶结构清晰,无或轻度细胞变性、坏死及炎性细胞浸润。Masson染色结果显示,A组和B组肝组织可见汇管区较多纤维结缔组织增生,出现不同程度小叶内纤维化;C组肝组织无明显异常病理改变。A、B、C组肝组织中TGF⁃β1（P < 0.001）、p38MAPK（P < 0.01）及BMP⁃7蛋白（P < 0.05）表达水平差异均有统计学意义,A组和B组TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平均显著高于C组（P均< 0.05）,B组TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平亦显著高于C组（P均< 0.05）。TGF⁃β1、p38MAPK及BMP⁃7蛋白表达水平均与肝纤维化程度呈正相关（r = 0.866、0.702、0.801,P均< 0.05）,不同纤维化程度肝组织中TGF⁃β1（F = 72.580,P < 0.01）、p38MAPK（[χ2] = 31.705,P < 0.01）及BMP⁃7蛋白（[χ2] = 48.388,P < 0.01）表达水平差异均有统计学意义。TGF⁃β1蛋白与p38MAPK、BMP⁃7蛋白表达水平均呈显著正相关（r = 0.607、0.702,P均 < 0.001）,BMP⁃7与p38MAPK蛋白表达水平亦呈显著正相关（r = 0.456,P < 0.001）。结论　TGF⁃β1、p38MAPK和BMP⁃7蛋白通过相互作用、共同介导了肝多房棘球蚴病肝纤维化发生。     

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

目的研究右美托咪啶对大鼠肺缺血再灌注损伤(IRI)中p38丝裂素活化蛋白激酶(p38MAPK)及肺组织高迁移率族盒蛋白1(HMGB1)表达的影响,为分析右美托咪啶的肺保护作用奠定基础。方法将36只SD大鼠随机分为三组各12只:A组行假手术处理;B组建立大鼠急性肺IRI模型;C组在造模前以盐酸右美托咪啶预处理。手术3h后处死,取肺组织病理染色后观察组织病理学变化、行酶联免疫吸附试验检测肺组织髓过氧化酶(MPO)活性、行Western Blotting法检测肺组织磷酸化p38MAPK蛋白及HMGB1蛋白的表达。结果与A组比较,B组肺组织出现明显病理学改变,MPO活性明显更强,磷酸化p38MAPK蛋白及HMGB1蛋白表达水平亦明显增加,上述差异均有统计学意义(P0.05);与B组相比,C组上述各指标均明显下降,差异亦有统计学意义(P0.05)。磷酸化p38MAPK蛋白及HMGB1蛋白表达水平与肺组织病理损伤评分及MPO活性均呈显著正相关(P0.05)。结论肺IRI时可能出现p38MAPK信号通路异常活跃、肺组织HMGB1过表达,右美托咪啶则能有效抑制p38MAPK信号通路及肺组织HMGB1表达,这可能是其发挥肺保护作用的机制之一。     

SB203580对烟雾暴露的哮喘大鼠的影响

目的 建立烟雾暴露的支气管哮喘(简称哮喘)大鼠模型,观察p38有丝分裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)抑制剂SB203580对其的治疗作用.方法 将Wistar大鼠随机分为4组,即正常对照组、哮喘组、烟雾暴露的哮喘组及SB203580干预组.动物肺功能仪测定大鼠呼气阻力、吸气阻力及肺顺应性,观察肺组织病理学改变,通过ELISA检测大鼠肺组织中IL-4、IL-5和IL-8的表达.结果 与烟雾暴露的哮喘组相比,SB203580干预组大鼠的气道阻力显著下降,肺顺应性显著升高,差异有统计学意义(P＜0.05);气道炎症明显减轻;肺组织中IL-4、IL-5和IL-8的含量显著下降,差异有统计学意义(P ＜0.05).结论 p38 MAPK抑制剂SB203580可以改善烟雾暴露的哮喘大鼠的气道炎症,减轻其支气管收缩反应.     

SB203580对烟雾暴露的哮喘大鼠的影响

目的建立烟雾暴露的支气管哮喘(简称哮喘)大鼠模型,观察p38有丝分裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)抑制剂SB203580对其的治疗作用。方法将Wistar大鼠随机分为4组,即正常对照组、哮喘组、烟雾暴露的哮喘组及SB203580干预组。动物肺功能仪测定大鼠呼气阻力、吸气阻力及肺顺应性,观察肺组织病理学改变,通过ELISA检测大鼠肺组织中IL-4、IL-5和IL-8的表达。结果与烟雾暴露的哮喘组相比,SB203580干预组大鼠的气道阻力显著下降,肺顺应性显著升高,差异有统计学意义(P<0.05);气道炎症明显减轻;肺组织中IL-4、IL-5和IL-8的含量显著下降,差异有统计学意义(P<0.05)。结论 p38 MAPK抑制剂SB203580可以改善烟雾暴露的哮喘大鼠的气道炎症,减轻其支气管收缩反应。     

血管性痴呆小鼠海马p38丝裂原活化蛋白激酶免疫组织化学表达及多奈哌齐的干预作用

目的 探讨盐酸多奈哌齐对血管性痴呆(VD)小鼠海马p38丝裂原活化蛋白激酶(p38MAPK)表达的影响.方法 3月龄雄性昆明小鼠48只,随机分为假手术组、模型组和多奈哌齐治疗组,每组16只.模型组和多奈哌齐治疗组采用双侧颈总动脉线结扎,反复缺血-再灌注法制备VD小鼠模型,假手术组仅暴露双侧颈总动脉而不结扎,且尾部不放血.多奈哌齐治疗组模型制备第2天给予盐酸多奈哌齐3 mg·kg~(-1)·d~(-1)连续灌胃治疗4 w,假手术组、模型组给予生理盐水0.01 ml·kg~(-1)·d~(-1)灌胃.应用跳台实验和水迷宫实验观察小鼠行为学改变,应用免疫组织化学技术检测小鼠海马p38MAPK的表达变化.结果 多奈哌齐治疗组小鼠学习、记忆成绩较模型组明显提高(P＜0.05),其海马p38MAPK表达明显降低(P＜0.05).结论 盐酸多奈哌齐对海马p38MAPK表达的影响可能是提高VD小鼠学习、记忆成绩的分子机制之一.     

实验性结肠炎p38丝裂原活化蛋白激酶表达的研究

目的观察三硝基苯磺酸（TNBS）诱导的大鼠结肠炎结肠组织p38MAPK表达与激活及大鼠血清TNF-α、IL-10水平变化,探讨p38MAPK在实验性结肠炎中的作用与机制。方法20只SD大鼠随机分为正常对照组（N）与模型组（M）,TNBS／乙醇法构建结肠炎模型,观察炎症活动指数（DAI）、大体形态损伤指数（CMDI）、组织学损伤指数（TDI）,ELISA法检测血清TNF-α、IL-10水平,免疫组化染色检测大鼠结肠p38MAPK、p-p38MAPK表达。结果与N组相比,M组DAI、CMDI、TDI显著升高（P〈0．01）,血清TNF-α升高,IL-10水平下降（P〈0．01）,结肠组织p38MAPK表达增加（P〈0．05）,p-p38MAPK表达显著增加（P〈0．01）。结论p38MAPK在实验性结肠炎的表达与激活均有明显增加,可能通过调节TNF-α、IL-10等细胞因子的表达参与结肠炎的发病。     

Role of p38alpha MAPK in cardiac apoptosis and remodeling after myocardial infarction

Acute coronary occlusion results in ischemia-mediated death of cardiomyocytes. In the days and weeks following myocardial infarction (MI), left ventricular remodeling occurs that is characterized by persistent cardiomyocyte apoptosis, thinning and fibrosis at the site of infarction, ventricular chamber dilatation, and growth of remaining viable cardiomyocytes. The p38 mitogen-activated protein kinase (MAPK) signaling cascade has been implicated in the remodeling process. In this work, mice with cardiac-specific expression of a dominant negative mutant form of p38 MAPK (DN-p38alpha) were subjected to MI by occlusion of the left coronary artery. Acute ischemia area was determined by transthoracic echocardiography 2 h after MI surgery, and was found to be nearly identical in DN-p38 mice and their wild-type littermates. Seven days after MI, mice were subjected to repeat echocardiography and histological examination of infarct size. DN-p38 mice had markedly reduced infarct size and increased ventricular systolic function 7 days after MI when compared to wild-type littermates. In addition, DN-p38 mice had less cardiomyocyte apoptosis than wild-type mice in the infarct border zone. Recently, it was discovered that Bcl-X(L) deamidation occurs in vivo, and this results in Bcl-X(L) degradation that sensitizes cells to apoptosis by enhancing BAX activity. Bcl-X(L) deamidation was found to occur in the cardiac tissue of wild-type mice after MI, but was reduced in DN-p38 mice. These results establish that p38 MAPK activity is required for pathological remodeling after MI and suggest that p38 MAPK may promote cardiomyocyte apoptosis through Bcl-X(L) deamidation.     

p38MAPK反义寡核苷酸对鼠血管平滑肌细胞增殖的影响

目的：探讨丝裂素活化蛋白激酶p38(p38mitogen—activated protein kinase，p38MAPK)反义寡聚脱氧核苷酸(antisense oliodeoxynucleotide，AODN)对血管平滑肌细胞增殖的影响。方法：培养大鼠胸主动脉平滑肌细胞。通过脂质体帮染p38MAPK AODN到血管平滑肌细胞(VMSC)。另设p38MAPK正义寡聚脱氧核苷酸(SODN)对照组和空白对照组。用流式细胞仪检测细胞增殖。结果：AODN明显抑制血管紧张素I刺激的血管平滑肌细胞增殖(P＜0.05～＜0．01)，其抑制作用呈剂量依赖性。结论：p38MAPK反义寡聚脱氧核苷酸能抑制大鼠的VSMC增殖，提示VSMC增殖与p38信号途径有关。     

p38信号蛋白在乳腺癌组织中表达的研究

目的检测p38信号蛋白在人乳腺癌组织中的表达,探讨其与乳腺癌发展的关系。方法采用免疫组织化学S-P法,检测60例乳腺癌组织中p38信号蛋白的表达。结果38例有淋巴结转移的乳腺癌病例中29例p38表达阳性,阳性率76.3%;22例无淋巴结转移的病例中9例p38阳性表达,阳性率40.9%,两者差异有显著性(P<0.01)。p-p38在有淋巴结转移的病例中阳性率68.4%,在无淋巴结转移的病例中阳性表达率36.4%,差异有显著性(P<0.05)。结论p38信号传导途径在乳腺癌侵袭与转移中起关键作用,其蛋白表达与乳腺癌临床分期有关。     

Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy

Aims/hypothesis Inflammation and fibrosis are pathological mechanisms that are partially regulated by cell signalling through the p38 mitogen-activated protein kinase (MAPK) pathway. Elements of the diabetic milieu such as high glucose and advanced glycation end-products induce activation of this pathway in renal cells. Therefore, we examined whether p38 MAPK signalling is associated with the development of human and experimental diabetic nephropathy.Methods Immunostaining identified phosphorylated (active) p38 MAPK in human biopsies with no abnormality (n=6) and with Type 2 diabetic nephropathy (n=12). Changes in kidney levels of phosphorylated p38 were assessed by immunostaining and western blotting in mice with streptozotocin-induced Type 1 diabetes that had been killed after 0.5, 2, 3, 4 and 8 months, and in Type 2 diabetic db/db mice at 2, 4, 6 and 8 months of age.Results Phosphorylated p38 was detected in some intrinsic cells in normal human kidney, including podocytes, cortical tubules and occasional interstitial cells. Greater numbers of these phosphorylated p38+ cells were observed in diabetic patients, and phosphorylated p38 was identified in accumulating interstitial macrophages and myofibroblasts. A similar pattern of p38 activation was observed in both mouse models of diabetes. In mice, kidney levels of phosphorylated p38 increased (2–6 fold) following the onset of Type 1 and Type 2 diabetes. In both mouse models, interstitial phosphorylated p38+ cells were associated with hyperglycaemia, increased HbA₁c levels and albuminuria. Further assessment of streptozotocin-induced diabetic nephropathy showed that interstitial phosphorylated p38+ cells correlated with interstitial fibrosis (myofibroblasts, collagen).Conclusions/interpretation Increased p38 MAPK signalling is a feature of human and experimental diabetic nephropathy. Time course studies in mouse models suggest that phosphorylation of p38 plays a pathological role, particularly in the development of interstitial fibrosis.Abbreviations ECL enhanced chemiluminescence - MAPK mitogen-activated protein kinase - p-p38 phosphorylated p38     

泡球蚴感染对BALB/c小鼠肝细胞ERK1/2和p38表达变化的初步研究

目的通过检测ERK1/2和p38在泡球蚴感染小鼠肝组织中的表达,探讨其在肝泡球蚴病发生中的作用。方法采用半定量逆转录聚合酶链反应（RT-PCR）及免疫组织化学的方法检测16例感染组小鼠和16例对照组小鼠肝组织中的ERK1/2和p38的表达水平。结果感染组ERK1/2表达水平较对照组有统计学差异（P〈0.05）,p38的表达在感染组与对照组无统计学差异。结论在泡球蚴感染早期,肝细胞增殖占主导。     

Differential phosphorylation of p38 induced by apoptotic and anti-apoptotic stimuli in murine hepatocytes

AIM: To investigate the differential phosphorylation and activation of p38 in hepatocytes by pro-apoptotic Transforming Growth Factor-βi (TGF-β1), pro-survival factors Epidermal Growth Factor (EGF) and 12-0- tetradecanoylphorbol-13-acetate (TPA) and the potential mechanisms. METHODS: The phosphorylation and activation of p38 were determined by immunoblotting. Apoptosis was analyzed by morphological staining and observation, FACS analysis of sub-G1 content and DNA fragmentation assay. To quantitatively determine caspase activation, caspase activity assay was performed in vitro. RESULTS: TGF-β1-induced apoptosis was associated with the phosphorylation of p38, and SB202190, a specific inhibitor of p38, which was able to inhibit TGF-β1-induced caspase activation and apoptosis. TPA and EGF also blocked apoptosis induced by TGF-β1. Both of them induced the phosphorylation of p38. The results showed SB202190 had no effect on TGF-β1-induced phosphorylation of p38, but effectively inhibited both EGF and TPA-induced phosphorylation of p38. CONCLUSION: Pro-apoptotic TGF-β1, anti-apoptotic TPA and EGF induce the phosphorylation of p38 through different mechanisms that can be distinguished by SB202190. The data suggest that TPA and EGF-induced p38 phosphorylation is through an autophosphorylation-dependent mechanism. Since p38 phosphorylation induced by TGF-β1 plays an important role in caspase activation and apoptosis, TPA and EGF-induced p38 phosphorylation may not be requisite for their anti-apoptotic function.     

熊果酸对高血压大鼠心肌纤维化及p38活化的影响

目的:观察熊果酸(UA)对高血压大鼠心肌纤维化的影响。方法:行腹主动脉结扎构建高血压大鼠心肌纤维化模型,实验大鼠分为假手术组、模型组、UA低、中、高剂量组[分别为10 mg/(kg·d)、20 mg/(kg·d)、40 mg/(kg·d)],每日灌胃给药1次。干预2个月后,测定血压、心脏重量指数(HMI)、左室重量指数(LVMI)、心功能指数、心肌细胞横径、Ⅰ型胶原蛋白表达和胶原体积分数。免疫印迹法测定p38磷酸化。免疫沉淀法测定p38活性。结果:UA能显著降低模型组心肌p38磷酸化及活性,下调血压、CHMI、LVMI、心肌细胞横径、Ⅰ型胶原蛋白表达和胶原体积分数,抑制心肌纤维化导致的心功能下降。结论:UA能抑制高血压大鼠心肌纤维化,抑制p38活化是其机制之一。