缺血预处理星形胶质细胞GDNF抑制p38MAPK信号通路减轻神经元凋亡

目的研究缺血预处理星形胶质细胞分泌GDNF抑制p38MAPK信号通路发挥脑保护作用。方法原代培养神经元及星形胶质细胞,给予缺血预处理,将星形胶质细胞培养基制备成条件培养基,沉默GDNF基因的培养基作为另一种条件培养基,将神经元分为对照组、预处理组、预处理+缺血组、缺血组,应用不同条件培养基孵育神经元,流式细胞术检测神经元凋亡,Western Blot法检测神经元p38MAPK及p-p38MAPK的表达。结果预处理+缺血组和缺血组神经元凋亡率明显增高(P<0.05),加入ACM2后凋亡率较ACM1和ACM3两组均减低(P<0.05)。每组神经元的p38MAPK蛋白表达均无明显变化(P>0.05);预处理+缺血组及缺血组p-p38MAPK的蛋白表达均明显高于对照组和预处理组(P<0.05),预处理+缺血组p-p38MAPK的蛋白表达均较缺血组低(P<0.05),加入ACM2组的p-p38MAPK蛋白表达低于ACM1和ACM3两组(P<0.05)。结论缺血预处理后星形胶质细胞分泌GDNF抑制p38MAPK信号通路的激活从而减少神经元凋亡,起到脑保护作用。     

Interleukin-1beta-induced transdifferentiation of renal proximal tubular cells is mediated by activation of JNK and p38 MAPK

Interleukin (IL)-1beta induces renal tubular epithelial cells to transdifferentiate to myofibroblasts, which express alpha-smooth muscle actin (alpha-SMA). To understand the signal transduction mechanisms involved in transdifferentiation, we examined the roles of mitogen-activated protein kinases (MAPKs) in IL-1beta-stimulated alpha-SMA expression and cell migration in the HK-2 human renal proximal tubular cell line. IL-1beta induced the transdifferentiation of renal proximal tubular cells, which was characterized by upregulated expression of alpha-SMA and increased cell migration. In addition, IL-1beta increased the activity of the three members of the MAPK family, ERK, JNK and p38 MAPK, in these cells. Both SP600125, a specific inhibitor of JNK, and SB203580, a specific inhibitor of p38 MAPK, suppressed the IL-1beta-induced expression of alpha-SMA and cell migration, but these effects were not observed with PD98059, a specific inhibitor of ERK. These results suggest that IL-1beta-induced HK-2 cell transdifferentiation is mediated, at least in part, through the activation of the JNK and p38 MAPK signaling pathways.     

p38 MAPK抑制物对大鼠心肌缺血再灌注损伤的保护作用及凋亡信号通路的影响

目的探讨p38 MAPK抑制物SB20358(SB)对心肌缺血再灌注(I/R)损伤的保护作用及凋亡信号通路的影响。方法选择45只250~300 g雄性SD大鼠,通过阻断其左冠状动脉前降支(LAD)30 min再灌注180 min制备I/R损伤模型。随机分3组(n=15):溶剂对照组(Vehicle组)、低剂量SB预处理组(SB-L组)和高剂量SB预处理组(SB-H组);同时选取15只同周龄SD大鼠仅穿线但不结扎(Sham组)。SB-L组和SB-H组分别于LAD结扎前30 min注射50μg/kg、100μg/kg SB,其余两组注射等体积的生理盐水。分别在术前(T0)、缺血30 min后(T1)、再灌注60 min(T2)、120 min(T3)及180 min后(T4)检测各组血浆肿瘤坏死因子(TNF-α)水平及I/R后的心功能情况[舒张末期压力(LVEDP)、左室收缩期平均压(LVSP)、短轴缩短率(FS)和射血分数(EF)],处死大鼠并通过TTC染色分析缺血程度和梗死程度,将心脏组织包埋并采用HE染色观察各组的心肌形态学变化,同时采用Western blot检测心肌梗死区p38及其磷酸化形式的p-p38的蛋白水平。结果与Sham组相比,Vehicle组除T0外的I/R其余时间点的TNF-α水平均升高,LVSP、FS和EF均降低,LVEDP、心肌p-p38/p38值及缺血和梗死程度均升高(P0.05),心肌肌纤维出现断裂溶解及坏死,心肌间质出现水肿且间隙增大,出现坏死灶;给予SB处理后可减轻以上异常指标及心肌病理改变,与Vehicle组的差异均有统计学意义,但仍与Sham组有差异(P0.05)。SB-H组的改善效果优于SB-L组(P0.05)。结论 SB对大鼠心肌I/R损伤有改善作用,可降低心肌缺血及梗死程度,改善心功能和炎症反应并抑制p38 MAPK信号通路活化。     

周期性张应力诱导成纤维细胞凋亡中p38MAPK信号通路的作用

背景:当牙齿受异常咬合力时会导致牙体吸收、牙周组织的大量破坏.目的:研究牙周膜成纤维细胞在受到周期性张应力刺激后是否发生凋亡及p38MAPK信号通路是否参与该凋亡过程.方法:取4～7代成纤维细胞,同步化后随机分为对照组、加力组和SB203580组.加力组和SB203580组细胞加载力值为12%表面应变率,加力频率为6个循环/min,即5 s拉伸,5 s松弛.SB203580组细胞在加力前1 h加入终浓度为20 mmol/L的p38MAPK抑制剂SB203580.分别在加力6,12,24 h,取各组细胞,流式细胞仪检测细胞凋亡,RT-PCR检测细胞凋亡基因bax mRNA的表达.结果与结论:与对照组比较,加力后成纤维细胞凋亡率及bax mRNA表达增加(P < 0.05),且随着加力时间的延长而增强,12 h达高峰,之后逐渐下降.与加力组比较,SB203580组对应时间点细胞凋亡减少(P < 0.05),bax mRNA表达降低.说明细胞受到力学刺激会发生凋亡,而丝裂原活化蛋白激酶p38MAPK信号通路参与了该凋亡过程.     

周期性张应力诱导成纤维细胞凋亡中p38MAPK信号通路的作用

背景：当牙齿受异常咬合力时会导致牙体吸收、牙周组织的大量破坏。目的：研究牙周膜成纤维细胞在受到周期性张应力刺激后是否发生凋亡及p38MAPK信号通路是否参与该凋亡过程。方法：取4～7代成纤维细胞,同步化后随机分为对照组、加力组和SB203580组。加力组和SB203580组细胞加载力值为12%表面应变率,加力频率为6个循环/min,即5s拉伸,5s松弛。SB203580组细胞在加力前1h加入终浓度为20mmol/L的p38MAPK抑制剂SB203580。分别在加力6,12,24h,取各组细胞,流式细胞仪检测细胞凋亡,RT-PCR检测细胞凋亡基因baxmRNA的表达。结果与结论：与对照组比较,加力后成纤维细胞凋亡率及baxmRNA表达增加（P〈0.05）,且随着加力时间的延长而增强,12h达高峰,之后逐渐下降。与加力组比较,SB203580组对应时间点细胞凋亡减少（P〈0.05）,baxmRNA表达降低。说明细胞受到力学刺激会发生凋亡,而丝裂原活化蛋白激酶p38MAPK信号通路参与了该凋亡过程。     

应激后大鼠下丘脑磷酸化p38MAPK的变化及电针足三里穴的调节作用

目的 观察应激对大鼠下丘脑磷酸化p38MAPK的影响及电针足三里穴的调节作用。方法将28只Wistar大鼠随机分为对照组、束缚应激组和束缚应激 电针组，后2组再根据束缚解除后及电针足三里穴位治疗后不同时间点分别分为3个亚组。电针治疗采用频率为5～12Hz的疏密波，治疗总时间30min。于相应时间点处死各组大鼠，采用Western印迹杂交法观察其下丘脑内磷酸化p38MAPK的变化。结果束缚应激组大鼠下丘脑内p38MAPK磷酸化水平明显高于对照组，且在束缚应激解除后3h仍保持在较高水平；应激大鼠经电针足三里穴处理后，下丘脑内磷酸化p38MAPK与束缚应激组相比明显回落，这种调节作用可持续到电针治疗结束后3h。结论束缚应激能引起下丘脑应激信号转导系统中p38MAPK的磷酸化，这可能是应激活动过程中的重要事件之一。电针足三里穴对下丘脑内磷酸化p38MAPK的调节作用可能与下丘脑-垂体-肾上腺轴的活动有关。     

大承气汤对脓毒症大鼠p38MAPK信号转导通路的影响

目的 观察大承气汤对脓毒症大鼠肝脏p38丝裂原活化蛋白激酶(p38MAPK)表达水平的影响,进一步揭示大承气汤治疗脓毒症的机制.方法 将60只健康雄性SD大鼠随机分为假手术组(n=20)、脓毒症组(n=20)、大承气汤组(n=20),应用大鼠盲肠结扎穿孔(CLP)复制脓毒症模型.假手术组开腹轻扰肠管后关腹,脓毒症组、大承气汤组均为脓毒症模型.大承气汤组在术前2 h和术后每4 h予以大承气汤灌胃.分别于术后2、6、12、24 h每组取5只大鼠,腹主动脉采血,用ELISA方法 检测大鼠血浆IL-6、TNF-α浓度,取肝组织进行免疫组化检测及观察p38MAPK表达.结果 与脓毒症组比较,大承气汤组大鼠肝脏p38MAPK表达水平受到抑制,炎症因子释放减少(P<0.05).结论 大承气汤对脓毒症大鼠的肝脏产生保护作用,可能是由于抑制大鼠肝脏p38MAPK表达来实现的.     

p38MAPK信号转导通路与肿瘤关系的最新研究进展

丝裂原活化蛋白激酶(MAPK)级联是细胞内广泛存在的一类丝/苏氨酸蛋白激酶超家族,其亚族主要包括细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶/应激激活蛋白激酶(JNK/SAPK)和p38MAPK。他们主要是将细胞外信号转入细胞核内并引起相应变化的重要信号通路,调节细胞生长、分化、对环境的应激适应、炎症反应等多种细胞生理/病理过程。迄今为止各类研究发现,p38MAPK可介导应激、炎性因子及生长因子等多种刺激引起的细胞反应,也可以通过下游效应蛋白磷酸化而改变基因的表达水平,获得不同的细胞效应应答,参与各种肿瘤细胞的发生、侵袭、转移和耐药等过程,故阐明p38MAPK信号通路参与不同肿瘤的调控机制,将为不同肿瘤的诊治过程提供新的门径。     

Hypertonic saline inhibits neutrophil (PMN) priming via attenuation of p38 MAPK signaling

Priming of the neutrophil cytotoxic response is central to the pathogenesis of early postinjury multiple organ failure (MOF). Platelet-activating factor (PAF) has been implicated as a key inflammatory mediator in postinjury neutrophil priming and requires p38 MAPK signaling to produce its biologic effects. Hypertonic saline (HTS) resuscitation decreases the postinjury inflammatory response following shock in animals and decreases receptor-mediated neutrophil (PMN) cytotoxic functions in vitro. We hypothesized that HTS attenuates PAF priming of the PMN cytotoxic response by interfering with PAF-mediated p38 MAPK signal transduction. Isolated PMNs were preincubated in isotonic buffer or HTS (Na+ = 180 mM), then primed with PAF. Neutrophil CD11b/CD18 expression was measured by flow cytometry. Receptor-dependent (fMLP), N-formyl-methionyl-leucyl-phenylalanine, fMLP) and receptor-independent (PMA) O2- production was measured by reduction of cytochrome c in resting and PAF primed PMNs. Total p38 MAPK protein PAF-mediated p38 MAPK activation was assessed by western blot of PMN lysates. Clinically relevant levels of HTS attenuated PAF-mediated beta2-integrin expression. While HTS attenuated receptor-dependent (fMLP and PAF/fMLP) O2- production, receptor-independent (PMA) O2- production was unaffected. Conversely, HTS attenuated PAF priming of PMA-mediated O2- production. PAF and HTS did not alter total cellular p38 MAPK content. Clinically relevant levels of HTS alone did not activate p38 MAPK but inhibited PAF mediated p38 MAPK activation. HTS attenuates PAF priming of the PMN cytotoxic response by altering intracellular signal transduction. Therefore, HTS resuscitation may attenuate postinjury PMN priming and ultimately the risk of developing MOF.     

p38MAPK通路相关因素与妊娠免疫耐受

妊娠是母体免疫系统对胎儿父系抗原发生免疫耐受的过程。母胎免疫耐受平衡破坏,将导致子痫前期、流产、胎儿宫内生长迟缓等病理性妊娠。文中从吲哚胺2,3-过氧化物酶、血红素加氧酶-1调控p38丝裂原活化激酶(p38MAPK)调节树突细胞功能的角度阐述免疫系统在妊娠中的作用。     

A novel vasculo-angiogenic effect of cilostazol mediated by cross-talk between multiple signalling pathways including the ERK/p38 MAPK signalling transduction cascade

Cilostazol is an anti-platelet agent with vasodilatory activity that acts by increasing intracellular concentrations of cAMP. Recent reports have suggested that cilostazol may promote angiogenesis. In the present study, we have investigated the effect of cilostazol in promoting angiogenesis and vasculogenesis in a hindlimb ischaemia model and have also examined its potential mechanism of action in vitro and in vivo. We found that cilostazol treatment significantly increased colony formation by human early EPCs (endothelial progenitor cells) through a mechanism involving the activation of cAMP/PKA (protein kinase A), PI3K (phosphoinositide 3-kinase)/Akt/eNOS (endothelial NO synthase) and ERK (extracellular-signal-regulated kinase)/p38 MAPK (mitogen-activated protein kinase) signalling pathways. Cilostazol also enhanced proliferation, chemotaxis, NO production and vascular tube formation in HUVECs (human umbilical vein endothelial cells) through activation of multiple signalling pathways downstream of PI3K/Akt/eNOS. Cilostazol up-regulated VEGF (vascular endothelial growth factor)-A165 expression and secretion of VEGF-A in HUVECs through activation of the PI3K/Akt/eNOS pathway. In a mouse hindlimb ischaemia model, recovery of blood flow ratio (ipsilateral/contralateral) 14?days after surgery was significantly improved in cilostazol-treated mice (10?mg/kg of body weight) compared with vehicle-treated controls (0.63±0.07 and 0.43±0.05 respectively, P<0.05). Circulating CD34+ cells were also increased in cilostazol-treated mice (3614±670 compared with 2151±608 cells/ml, P<0.05). Expression of VEGF and phosphorylation of PI3K/Akt/eNOS and ERK/p38 MAPK in ischaemic muscles were significantly enhanced by cilostazol. Our data suggest that cilostazol produces a vasculo-angiogenic effect by up-regulating a broad signalling network that includes the ERK/p38 MAPK, VEGF-A165, PI3K/Akt/eNOS and cAMP/PKA pathways.     

p38MAPK信号通路在肢体缺血预处理脑保护中的作用

目的应用大鼠大脑中动脉缺血再灌注模型研究无创性远端肢体缺血预处理(RLIP)对大鼠脑缺血再灌注损伤的作用,探讨RLIP是否通过降低p38MAPK信号通路的活性抑制神经细胞凋亡发挥脑保护的作用。方法 36只健康雄性SD大鼠,体重200~250 g,随机分成3组(n=12):假手术组(sham组)、缺血再灌注组(I/R组)、无创远端肢体缺血预处理组(RLIP组)。(1)Sham组:分离右侧的颈总动脉、颈内动脉、颈外动脉,但不阻断血流。(2)I/R组:参照Longa的线栓法制作大脑中动脉缺血再灌注(MCAO)模型,阻断大鼠右侧大脑中动脉2 h后再灌注24 h。(3)RLIP组:在大鼠右后肢根部用改良的自制血压袖带施行远端缺血预处理,缺血5 min,再灌注5 min,共3个循环,RLIP后即刻行大鼠右侧大脑中动脉阻塞再灌注,步骤同前。三组大鼠均再灌注24 h后行神经功能缺陷评分(NDS);用TTC法测定脑梗死容积;HE染色观察海马CA1区椎体细胞的形态;免疫组织化学法测定海马CA1区P-p38MAPK蛋白、Caspase8蛋白及Caspase3蛋白的表达。结果 (1)神经功能缺陷评分:sham组无神经功能缺陷;RLIP组比I/R组评分降低,但两组24 h NDS评分中位数相同。(2)TTC染色:sham组无梗死体积,与I/R组相比,RLIP组脑梗死体积显著减小,差异有统计学意义(P<0.05)。(3)HE染色:sham组海马CA1区椎体细胞形态正常,排列整齐、致密,为2~3层,细胞核圆而大,染色呈浅蓝色。I/R组椎体细胞数明显减少,细胞体积缩小,细胞核碎裂、溶解、染色加深,间质水肿明显。与I/R组比较,RLIP组海马CA1区椎体细胞层次较清楚,数目多且细胞形态较完整,间质水肿较轻。(4)免疫组织化学结果:与I/R组比较,RLIP组P-p38MAPK蛋白、Caspase8蛋白和Caspase3蛋白表达显著减少(P<0.05),但两组蛋白的表达均明显高于sham组(P<0.05)。结论无创性RLIP对大鼠脑缺血再灌注损伤有保护作用,其机制可能与降低p38MAPK信号通路活性,减少Caspase8蛋白和Caspase3蛋白表达抑制神经细胞凋亡有关。     

创伤患者p38MAPK信号通路的变化及其临床意义

目的 探讨不同创伤程度患者体内p38MAPK信号通路的变化及意义.方法不同创伤程度住院患者150例,根据创伤度评分(ISS)分为三组:ISS≤15分(L-ISS)组、ISS 16～25分(M-ISS组)、ISS≥25分(H-ISS)组,每组50例,同时选取30名健康献血者作为对照组.不同创伤程度患者在创伤后6 h内和第1、3、5、7天分别采集外周血,对照组采集外周血一次,采用实时定量PCR(RQ-PCR)和蛋白免疫印迹法(Western-blot)检测白细胞中p38MAPK的基因表达、蛋白表达及活化(磷酸化)水平变化.结果创伤6 h内不同创伤程度患者血液中p38MAPK的基因表达与正常人比较均显著增加(P＜0.05),在创伤后第1天达到高峰(P＜0.01),并持续高表达至第7天(P＜0.05);在创伤后第1天不同创伤程度患者体内的p38MAPK蛋白表达和活化(磷酸化)水平也显著增强(P＜0.05);进一步的试验发现,p38MAPK的基因表达、蛋白表达和活化(磷酸化)程度都随创伤级别的增加而升高(P＜0.05).结论创伤患者体内的p38MAPK信号通路被激活,且创伤程度与p38MAPK的表达和活化呈正相关,表明p38MAPK信号通路在创伤的病理机制中发挥重要作用.     

黄芪三七合剂通过影响p38 MAPK的表达改善CKD大鼠肾脏纤维化

目的探讨黄芪三七合剂通过调控p38 MAPK的表达改善慢性肾脏疾病(CKD)大鼠肾脏纤维化的作用。方法将雄性SD大鼠60只分为3组:健康组(NOR,n=20)、模型组(CKD,n=20)、黄芪三七合剂组(AR,n=20)。CKD组和AR组采用腺嘌呤灌胃方法建立大鼠CKD模型,建模后AR组予以黄芪三七合剂(3mL/d)灌胃,NOR组和CKD组予以同等体积生理盐水灌胃,连续4周。于建模后2、4周分别处死各组大鼠10只,检测肾功能,行肾脏HE和Masson染色观察肾脏病理及纤维化改变;免疫组织化学法测定肾脏p38 MAPK蛋白表达水平。结果与NOR组相比,CKD组的血尿素氮及血肌酐水平均显著升高(P0.01),与CKD组比较,AR组大鼠肾功能指标明显改善(P0.05)。CKD组大鼠肾脏出现肾小管管腔扩张,坏死,大量炎性细胞浸润,大量肾间质纤维化及肾间质胶原沉积的改变,与CKD组比较,AR组肾脏病理损害减轻,胶原沉积面积比明显减少(P0.05)。免疫组织化学结果提示CKD组和AR组的p38 MAPK蛋白表达均显著高于NOR组(P0.01),而AR组低于CKD组(P0.05)。结论黄芪三七合剂对大鼠肾脏损伤具有保护作用,其改善纤维化的作用可能是通过减弱p38MAPK蛋白表达发挥。     

p38对放线菌酮经线粒体途径诱导HL-60细胞死亡的影响

目的研究 p38对放线菌酮(CHX)经线粒体途径诱导 HL-60细胞死亡的影响。方法利用 p38持异性阻断剂 SB203580(SB)阻断 HL-60细胞 p38途径,分别设对照组、单纯 SB 组、CHX组和 CHX 联合 SB 组;于处理6,9,12,18,24 h 利用碘化丙锭(PI)染色流式细胞术检测亚二倍体峰细胞比率;于处理6和18 h 进行膜联蛋白Ⅴ(Annexin Ⅴ)/PI 双标流式细胞术测定凋亡和坏死细胞比率;于处理18 h 利用 JC-1染色流式细胞术分析,通过对 FL2的划分比较不同处理时间高 JC-1集合体量细胞比率;测定细胞 JC-1集合体(FL2)和 JC-1单体(FL1)平均荧光强度,并计算线粒体膜电势(△Ψ_m,FL2/FL1)。结果在 CHX 处理6 h HL-60细胞亚二倍体峰细胞比率显著高于对照组,在此过程中阻断 p38途径则在处理9 h 开始亚二倍体峰细胞比率显著高于 CHX 组。处理18 h 凋亡细胞比率:CHX组[(27.9±0.52)%]和 CHX 联合 SB 组[(28.54±1.38)%]均显著高于对照组[(2.45±0.65)%](P<0.01);CHX 联合 SB 组与 CHX 组比较差异无统计学意义(P>0.05)。处理18 h 坏死细胞比率:CHX 组和 CHX 联合 SB 组均显著高于对照组(P<0.01);CHX 联合 SB 组显著高于 CHX 组(P<0.01)。此外,CHX 组和 CHX 联合 SB 组高 JC-1集合体细胞比率均显著低于对照组(P<0.01),CHX联合 SB 组高 JC-1集合体细胞比率显著低于 CHX 组(P<0.01)。处理18 h 时各实验组△Ψ_m CHX 组(0.17+0.01)和 CHX 联合 SB 组(0.05±0.003)均显著低于对照组(0.38±0.02)(P<0.01),CHX 联合 SB 组△Ψ_m 显著低于 CHX 组(P<0.01)。结论 CHX 可诱导 HL-60细胞凋亡和线粒体去极化,在该过程中阻断 p38途径可使线粒体的去极化作用增强,本模型中 p38途径可能与 HL-60细胞的坏死密切相关。     

Feeding-induced hepatokine,Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte–derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet–induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.     

抑制p38 MAPK通路对大鼠癫痫发作引起海马神经元损伤的保护作用

目的探讨抑制p38 MAPK通路对减轻红藻氨酸诱导的颞叶癫痫发作引起大鼠海马神经元所造成损害的作用和机制.方法经侧脑室给予不同剂量(0,0.01,0,1,1 μg)SB203580(p38 MAPK特异性抑制剂)预处理,30 min后再予红藻氨酸制作大鼠颞叶癫痫持续状态模型.7 d后采用Nissl染色方法观察海马各区的锥体细胞和颗粒细胞的情况.结果红藻氨酸注射7 d后CA3区可见大量锥体细胞缺失,尚存细胞变性,伴局限性颗粒细胞增多,呈放射状分布.CA1区受累较轻,但也存在一定程度的细胞脱失.预先给予SB203580(0.1μg以上剂量)处理的动物以上变化明显减轻.假手术大鼠海马各区有大量正常致密锥体细胞,未见细胞脱失.结论大鼠侧脑室内注射红藻氨酸引起全身痉挛性癫痫持续状态对海马神经元造成损害,而抑制p38 MAPK通路,对海马神经元起一定保护作用.     

EV71感染对小鼠脑组织p38MAPK信号通路影响的研究

目的研究肠道病毒71(EV71)感染对小鼠脑组织p38MAPK信号通路的影响。方法利用实验室筛选出的具有较强致病能力的EV71-GZCH43-3株,采用不同的病毒滴度(103PFU/ml,105PFU/ml,107PFU/ml)感染2周龄的ICR幼鼠,建立轻、中、重三种不同程度的幼鼠感染模型,病理切片观察其肺组织病理变化;利用流式细胞术检测感染模型幼鼠中CD4+CD25+Foxp3+Treg细胞的变化情况;反转录酶-聚合酶链式扩增反应(RT-PCR)方法检测p38MAPK信号途径基因的表达变化;酶联免疫分析法(ELISA)检测小鼠血清中肿瘤坏死因子α(TNF-α)、干扰素(IFN-γ)水平的变化情况。结果成功建立轻、中、重三种不同感染滴度的EV71感染幼鼠模型,其肺组织明显充血;流式细胞术结果显示随着病毒感染滴度的增加,Treg细胞的数目明显增加;ELISA结果表明随病毒滴度增加IFN-γ表达量增加,高滴度组大约是对照组的30倍;TNF-α先随病毒滴度增加而略有降低,随后在高滴度组又明显升高。结论表明EV71感染可能通过影响p38MAPK信号途径基因的表达而间接调节TNF-α和IFN-γ体内表达,诱导宿主病理性免疫反应,引起宿主免疫功能的紊乱。