TLR4-p38MAPK信号通路在金黄色葡萄球菌感染人巨噬细胞系U937过程中的表达及意义

目的观察金黄色葡萄球菌感染人巨噬细胞系U937细胞后信号通路Toll样受体4(TLR4)-p38蛋白激酶(p38MAPK)的表达及意义。方法体外培养人巨噬细胞系U937细胞,感染0、30、60和90 min时收集细胞,应用Western blot法检测各组TLR4和p38MAPK蛋白表达的变化;在另一实验中,分为对照组、金黄色葡萄球菌感染60 min组及p38MAPK抑制剂SB203580 5 mg/m L干预组、SB203580 10 mg/m L干预组,应用Western blot法检测各组TLR4和p38MAPK蛋白表达的变化。结果随着感染时间的延长,TLR4和p38MAPK蛋白的表达逐渐增加;给予SB203580抑制剂后,TLR4和p38MAPK蛋白的表达明显减弱。结论金黄色葡萄球菌感染U937细胞可引起TLR4-p38MAPK信号通路的活化,而SB203580对其有明显的抑制作用,证明TLR4-p38MAPK信号通路与金黄色葡萄球菌感染U937细胞密切相关。     

阿霉素诱导胰腺癌BxPC-3细胞凋亡过程中p38MAPK的表达

目的研究阿霉素诱导胰腺癌细胞凋亡过程中p38MAPK表达的变化,探讨p38MAPK在其中的作用。方法用膜联蛋白V-PI(annexinV-PI)染色及流式细胞技术分析阿霉素及应用p38MAPK抑制剂SB203580对胰腺癌细胞凋亡的影响,同时利用免疫细胞化学法观察经阿霉素及SB203580处理人胰腺癌BxPC-3细胞后,p38MAPK的表达水平。结果SB203580(20μmol/L)干预组胰腺癌BxPC-3细胞凋亡率为(20.1±1.4)%,阿霉素作用24 h后诱导胰腺癌BxPC-3细胞凋亡,凋亡率为(31.1±2.7)%,加用SB203580抑制p38MAPK通路后可增强阿霉素诱导的凋亡作用,凋亡率达(40.4±2.6)%。采用单因素方差分析F=136.79,组间比较组与组之间差异有统计学意义。以20μmol/L阿霉素作用BxPC-3胰腺癌细胞24 h后可见p38MAPK在细胞染色后呈现深褐色颗粒散在分布于部分或整个细胞核及细胞质内,联合应用SB203580后可见p38MAPK表达颗粒密度减低,数量减少。结论阿霉素可以活化p38MAPK通路,p38MAPK可能起到保护胰腺癌BxPC-3细胞逃避阿霉素诱导的凋亡,阻断该通路可增强阿霉素诱导胰腺癌细胞凋亡的作用。     

克罗米酚对骨髓间质干细胞增殖和向成骨细胞分化的影响

目的　在离体条件下研究克罗米酚(CLO)对小鼠骨髓间质干细胞(BMSCs)增殖和向成骨细胞分化的影响。方法　在含经活性炭吸附的 10%血清的无酚红α MEM中加入β 磷酸甘油和维生素C诱导小鼠BMSCs向成骨细胞分化,同时加入 0 1nmol·L-1至 10nmol·L-1CLO处理细胞。用细胞计数来反映细胞增殖情况;测定碱性磷酸酶 (ALP)活性与钙的沉积量反映细胞向成骨细胞分化状态;用试剂盒来检测一氧化氮 (NO)的产物。结果　CLO ( 0 1 ~10nmol·L-1 )呈剂量依赖性地增加小鼠BMSCs的数目,ALP活性和钙的沉积量,同时培养基中NO代谢产物明显增加。分别加入雌激素受体 (ER)拮抗剂ICI182, 780 (0 1μmol·L-1 )及一氧化氮合酶抑制剂L NAME( 6mmol·L-1 )均可阻止CLO促进BMSCs的增殖及向成骨细胞分化的作用,并取消NO代谢产物的增加。结论　CLO在 0 1 ~10nmol·L-1剂量范围内具有雌激素样受体激活效应,可通过ER/NO途径促进小鼠骨髓间质干细胞的增殖及向成骨细胞分化。     

唑来膦酸盐通过p38 MAPK信号通路调控高糖微环境下成骨细胞分化

目的 探讨唑来膦酸盐（ZOL）对高糖微环境下小鼠前成骨细胞MC3T3-E1成骨分化的影响及p38丝裂原活化蛋白激酶（p38 MAPK）通路的调节作用。方法 体外培养MC3T3-E1细胞并分为低糖（LG）组、LG+ZOL组、高糖（HG）组、HG+ZOL组。ZOL为0.1μmol/L,LG、HG的葡萄糖浓度分别为5.5 mmol/L和16.5 mmol/L。采用四甲基偶氮唑蓝（MTT）法检测细胞增殖水平;鬼笔环肽染色观察细胞骨架;试剂盒检测细胞碱性磷酸酶（ALP）活性;茜素红染色检测细胞矿化结节生成情况;免疫荧光法检测Wnt5a、p38 MAPK的荧光表达强度。另设HG+ZOL+p38 MAPK通路抑制剂（SB203580）组,SB203580为10μmol/L。Western blot检测5组细胞中Wnt5a、p38 MAPK、磷酸化p38丝裂原活化蛋白激酶（p-p38 MAPK）、骨形态发生蛋白2(BMP2)和Ⅰ型胶原蛋白（COLⅠ）的表达水平。结果 4组细胞增殖水平差异无统计学意义（P>0.05）。与LG组比较,LG+ZOL组细胞骨架清晰程度,ALP活性,茜素红矿化结节生成,W...     

DATS通过p38MAPK通路抑制LPS诱导的小鼠MH-S细胞TNF-α及IL-1β表达

目的探讨p38MAPK在二烯丙基三硫(DATS)抑制脂多糖(LPS)诱导小鼠肺泡巨噬细胞促炎细胞因子表达中的作用。方法体外培养MH-S细胞,用DATS和(或)LPS进行干预,Western blot检测细胞p38及磷酸化p38(p-p38)的表达;用LPS和(或)SB203580孵育细胞,反转录PCR检测细胞中TNF-α、IL-1βmRNA表达,Western blot检测细胞磷酸化(p-IκB)及非磷酸化IκB的表达。结果 LPS刺激MH-S细胞可导致p-p38表达增加,呈时间依赖性;用DATS(0.1、0.5、2.5、5.0 mg.L-1)预处理细胞30 min后再给予LPS刺激,p-p38表达呈剂量依赖性下降;单独DATS对p-p38表达无明显影响。p38特异性抑制剂SB203580可剂量依赖性地抑制LPS诱导的p-IκB蛋白、TNF-α及IL-1βmR-NA表达。结论 DATS可通过抑制p38MAPK通路抑制IκB磷酸化及NF-κB活化,进而下调LPS诱导小鼠肺泡巨噬细胞TNF-α、IL-1βmRNA表达。     

阻断p38丝裂原活化蛋白激酶信号通路对高糖培养肾小球系膜NF-κB信号通路调控影响

目的:探讨阻断p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinases,p38MAPK)信号通路对高糖培养肾小球系膜NF-κB信号通路调控影响。方法:大鼠系膜细胞株分别培养在正常糖浓度(5.5 mmol/L,对照组),高糖浓度(25 mmol/L,高糖组)及25 mmol/L葡萄糖+10μmol/L p38 MAPK特异性抑制剂SB203580(SB组)。CCK-8测定系膜细胞增殖;Phospho-ELISA法分别检测胞浆及胞核内p38MAPK、磷酸化p38 MAPK蛋白和总NF-κBp65、活性NF-κB p65、磷酸化NF-κB p65(S276)表达。结果:与正常对照组比较,高糖组系膜细胞出现增殖增加;胞浆及胞核内磷酸化p38MAPK蛋白表达上调;胞核内NLS-NF-κB、Ser276-NF-κB的表达增加;SB203580干预则能逆转这一变化。结论:阻断p38 MAPK信号通路能下调高糖培养的系膜细胞NF-κB信号通路的活化,进而抑制系膜细胞的异常增殖。     

p38 MAPK及其抑制剂在胰岛素调节GLUT4活性中的作用

目的:探讨p38丝裂原活化蛋白激酶(p38 MAPK)及其抑制剂SB203580在胰岛素调节葡萄糖转运子4(GLUT4)活性机制中的作用。方法:分别测定胰岛素和SB203580孵育条件下骨骼肌细胞p38 MAPK的磷酸化水平和活性;检测p38 MAPK或SB203580是否与GLUT4直接结合;并测定SB203580对光化学标记细胞膜上的GLUT4的影响。结果:与胰岛素孵育0min时相比,100nmol/L胰岛素使p38 MAPK磷酸化水平增加,最大值为0min时的(2.43±0.21)倍;胰岛素还使p38α和p38βMAPK的活性分别增加了(10.13±0.48)和(7.92±2.17)倍;SB203580可抑制胰岛素的作用;p38 MAPK在体内不与GLUT4直接结合;SB203580仅抑制胰岛素刺激下的GLUT4光化学标记。结论:p38MAPK或SB203580不直接与GLUT4结合;对SB203580敏感的分子参与了胰岛素调节GLUT4活性的作用。     

SB203580对缺氧/复氧损伤诱导的大鼠肾小管上皮细胞凋亡的保护作用及其机制

目的研究SB203580(吡啶咪唑类抗炎药)对大鼠肾小管上皮细胞凋亡的保护作用及机制。方法SD大鼠肾小管上皮细胞原代培养,取第2代细胞实验;共分为3组:对照组,正常培养细胞;模型组,细胞缺氧1 h后,复氧6、12、24、48 h培养;SB203580预处理组,在缺氧损伤前1 h,用不同剂量SB203580(0.2、2、20μmol·L~(-1))预处理细胞,尔后进行缺氧/复氧损伤处理,各细胞用Hoechst 33258、Tunnel染色、流式细胞仪及Western blot方法,观察缺氧/复氧后细胞凋亡及p38MAPK的磷酸化水平。结果与对照组相比,缺氧/复氧后,实验组细胞的凋亡率显著增加,且细胞内p38MAPK磷酸化水平明显升高;而应用SB203580预处理细胞,可显著降低实验组细胞的凋亡率及细胞内p38MAPK的磷酸化水平。结论SB203580通过抑制p38MAPK的活性,对缺氧/复氧诱导的肾小管上皮细胞凋亡有保护作用。     

β-蜕皮甾酮对高糖诱导的大鼠成骨细胞增殖、分化和凋亡的影响

目的探讨β-蜕皮甾酮对高糖诱导的大鼠成骨细胞增殖、分化和凋亡的影响及分子机制。方法将大鼠成骨细胞随机分为空白组(5.5 mmol·L-1葡萄糖)、模型组(25 mmol·L-1葡萄糖)、低、中、高剂量实验组(1,5,25μmol·L-1β-蜕皮甾酮+25 mmol·L-1葡萄糖)、p38 MAPK激活组(10μmol·L-1 anisomycin+25μmol·L-1β-蜕皮甾酮+25 mmol·L-1葡萄糖)、阴性对照组(与anisomycin等量的PBS+25μmol·L-1β-蜕皮甾酮+25 mmol·L-1葡萄糖)。细胞计数试剂盒8(CCK-8)检测细胞活性;流式细胞术检测细胞凋亡情况;用蛋白质印迹法检测Run相关基因2(RunX2)、碱性磷酸酶(ALP)、骨钙素(OCN)和磷酸化p38丝裂原活化蛋白激酶(p-p38 MAPK)蛋白表达。结果空白组、模型组、低、中、高剂量实验组、阴性对照组、p38 MAPK激活组大鼠成骨细胞活性分别为(102.41±5.34)%,(68.57±5.25)%,(75.36±7.06)%,(79.13±8.24)%,(83.20±8.89)%,(83.17±8.93)%,(71.11±6.16)%;细胞凋亡率分别为(4.23±0.56)%,(18.57±1.96)%,(13.08±1.34)%,(10.30±0.95)%,(8.25±1.08)%,(8.36±1.12)%,(16.48±1.56)%;RunX2蛋白表达水平分别为0.81±0.07,0.31±0.04,0.45±0.06,0.55±0.04,0.61±0.08,0.63±0.07,0.41±0.05;ALP蛋白表达水平分别为0.75±0.08,0.38±0.05,0.49±0.07,0.59±0.05,0.65±0.08,0.68±0.07,0.44±0.06;OCN蛋白表达水平分别为0.69±0.05,0.28±0.03,0.34±0.05,0.47±0.04,0.45±0.05,0.46±0.05,0.31±0.04;p-p38 MAPK蛋白表达水平分别为0.22±0.04,0.84±0.09,0.59±0.06,0.41±0.04,0.32±0.04,0.32±0.07,0.74±0.07;模型组与空白组相比,低、中、高剂量实验组与模型组相比,p38 MAPK激活组与阴性对照组相比,差异均有统计学意义(均P<0.05)。结论β-蜕皮甾酮可能通过抑制p38 MAPK信号通路促进大鼠成骨细胞增殖、分化,抑制细胞凋亡。     

铜绿假单胞菌通过MAPK信号传导通路诱导U937细胞表达IL-8

目的探讨铜绿假单胞菌(PA)活菌对不同分化状态的U937细胞表达IL-8的诱导作用及通过MAPK信号传导通路的调控机制。方法应用人单核白血病细胞系-U937细胞,采用ELISA和RT-PCR法对PA诱导不同分化状态的U937细胞IL-8蛋白分泌和其mRNA表达进行研究,并观察MAPKs抑制剂PD98059和SB203580对IL-8表达的影响。结果PA可促进U937细胞及PMA分化的U937细胞IL-8的mRNA及蛋白分泌,而且具有明显的量效和时效关系。分别用SB203580抑制p38MAPK通路、用PD98059抑制ERK通路,均能引起抑制剂浓度依赖的IL-8的表达(P<0.01)。结论PA以浓度和时间依赖的方式感染U937细胞,促进IL-8的分泌和mRNA表达,PA可能通过MAPK信号通路启动IL-8的高效表达和分泌。     

染料木素对离体豚鼠左室乳头肌收缩功能的影响

目的观察染料木素对离体豚鼠左室乳头肌收缩功能的影响,并探讨其作用机制。方法将离体豚鼠乳头肌置于装有KH液的灌流肌槽中,待平衡后,加入各种药物观察乳头肌收缩活动的变化。结果染料木素和异丙肾上腺素相似,可增强豚鼠左室乳头肌的收缩活动,染料木素(1、100μmol.L-1)的作用还具有明显的剂量依赖性。心得安(1μmol.L-1)和异搏定(0.5μmol.L-1)虽可明显阻断异丙肾上腺素(2μmol.L-1)的正性肌力作用,但对染料木素(100μmol.L-1)的心肌收缩增强效应无明显改变;同时发现染料木素(1、10μmol.L-1)对细胞外液Ca2+浓度升高而诱发的心肌收缩力增强也无明显影响。另外,它莫西芬(1μmol.L-1)可明显减弱染料木素的正性肌力作用,但正矾酸钠(1μmol.L-1)对其作用无明显影响。结论染料木素可增强心肌收缩活动,其作用与心肌细胞膜上的β肾上腺素能受体和钙通道激活以及酪氨酸激酶途径无关,可能与肌质网Ca2+的摄取和利用有关。     

Involvement of mitogen-activated protein kinases and protein kinase C in cadmium-induced prostaglandin E2 production in primary mouse osteoblastic cells

We previously reported that cadmium (Cd) induced prostaglandin E₂ (PGE₂) biosynthesis through the activation of cytosolic phospholipase A₂ (cPLA₂) and induction of cyclooxygenase 2 (COX-2) in primary mouse osteoblastic cells. In the present study, we further investigated the mechanism of PGE₂ production by Cd focusing on the main mitogen-activated protein kinase (MAPK) subfamilies that mediate prostaglandin synthesis, extracellular signal-regulated kinase (ERK1/2 MAPK), c-jun-amino-terminal kinase (JNK MAPK) and p38 MAPK, and protein kinase C (PKC) which is activated by Cd in several kinds of cells. Cd at 2 μM and above stimulated PGE₂ production in osteoblastic cells and its production was inhibited by the kinase-specific inhibitors PD98059, SB203580, curcumin, and calphostin C. Calphostin C also inhibited the production of PGE₂ by phorbol 12-myristate 13-acetate (PMA), which is a potent activator of PKC. PD98059 inhibited PGE₂ production stimulated by PMA as well as Cd, indicating that activation of PKC by ERK1/2 MAPK was necessary for Cd-stimulated PGE₂ production. Moreover, Cd stimulated the phosphorylation of these three MAPKs, and inhibition of the phosphorylation of ERK1/2 MAPK by calphostin C was also observed. On the other hand, Cd was found to phosphorylate cPLA₂ and the phosphorylation was inhibited by PD98059, indicating that cPLA₂ was activated by Cd through ERK1/2 MAPK and released arachidonic acid (AA), a substrate of COX-2, from membranous phospholipids. From these results, it was suggested that activation of each of the ERK1/2, p38, and JNK MAPK cascades in addition to that of PKC and cPLA₂ played an important role in the Cd-stimulated biosynthesis of PGE₂ in mouse osteoblastic cells.     

p38MAPK在戊地昔布诱导Eca109细胞凋亡中的调控作用

目的探讨p38MAPK信号转导途径在戊地昔布诱导食管癌Eca109细胞凋亡中的调控作用。方法将正常培养的人食管癌Eca109细胞随机分为正常对照组、戊地昔布组和戊地昔布+SB203580组;采用流式细胞术和DNA Ladder检测凋亡情况;RT-PCR检测p38mRNA的表达变化;流式细胞术和免疫细胞化学检测p38蛋白的表达变化。结果①戊地昔布能够诱导Eca109细胞发生凋亡,并呈剂量依赖性,而SB203580能够部分降低戊地昔布诱导的Eca109细胞的凋亡率;②戊地昔布能够上调Eca109细胞中p38mRNA和蛋白的表达,而戊地昔布+SB203580组p38mRNA和蛋白的表达下降;③p38蛋白表达与凋亡率呈正相关。结论戊地昔布能够通过部分激活p38MAPK信号途径诱导Eca109细胞发生凋亡。     

黄连素对高糖培养的大鼠肾小球系膜细胞FN及p38MAPK信号通路的影响

目的研究黄连素对高糖培养下大鼠肾小球系膜细胞细胞外基质成分纤维连接蛋白及p38MAPK信号通路的影响,进一步探讨黄连素抗糖尿病肾病的作用机制。方法实验分组:正常对照组、甘露醇组、高糖组、高糖+SB203580组、高糖+黄连素低剂量组、高糖+黄连素高剂量组共6组,观察黄连素对高糖培养下的大鼠肾小球系膜细胞纤维连接蛋白以及p38MAPK信号通路蛋白表达的影响。结果与高糖组相比,黄连素降低系膜细胞纤维连接蛋白的蛋白表达水平,抑制p38MAPK及其下游核转录因子CREB的磷酸化。结论黄连素抗糖尿病肾病的作用可能与其减少细胞外基质成分FN的积聚,抑制p38MAPK信号通路激活密切相关。     

oridonin部分通过TNFα信号转导途径诱导小鼠成纤维L929细胞凋亡

目的比较冬凌草甲素(oridonin)和TNFα诱导小鼠成纤维L929细胞凋亡的分子机制。方法MTT法、Hoechst33258荧光染色、DNA片断化分析和Western blot分析法。结果Oridonin和TNFα均能诱导L929细胞发生凋亡,其半数有效抑制浓度IC50分别为(24·8±1·2)μmol·L-1和(20·9±1·9)μg·L-1。Oridonin和TNFα均能引起L929细胞凋亡形态学变化,TNFα处理过的细胞在琼脂糖凝胶电泳上可见典型的凋亡DNA梯状条带,但是oridonin处理的细胞却不能,称之为非典型凋亡;caspase-3,-8抑制剂和caspase家族抑制剂能明显得促进25μmol·L-1oridonin和20μg·L-1TNFα诱导的L929细胞凋亡,caspase-9抑制剂只能促进oridonin诱导的L929细胞凋亡;ERK的抑制剂PD98059能明显的抑制oridonin和TNFα诱导的L929细胞凋亡,但是p38的抑制剂SB203580只能抑制TNFα诱导的L929细胞凋亡;在L929细胞中oridonin能促进内源性pro-TNFα的表达和其上游蛋白IκB的磷酸化。结论Oridonin通过激活转录因子NF-κB而促进内源性pro-TNFα的表达,并且部分通过细胞因子TNFα信号转到途径诱导L929细胞凋亡。     

Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) induces cell death through MAPK-dependent mechanism in osteoblastic cells

The present study was undertaken to determine the role of the mitogen-activated protein kinase (MAPK) subfamilies in cell death induced by PPARgamma agonists in osteoblastic cells. Ciglitazone and troglitazone, PPARgamma agonists, resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. But a PPARalpha agonist ciprofibrate did not affect the cell death. Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone-induced cell death was prevented by antioxidants, suggesting an important role of ROS generation in the ciglitazone-induced cell death. ROS generation and cell death induced by ciglitazone were inhibited by the PPARgamma antagonist GW9662. Ciglitazone treatment caused activation of extracellular signal-regulated kinase (ERK) and p38. Activation of ERK was dependent on epidermal growth factor receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death was significantly prevented by PD98059, an inhibitor of ERK upstream kinase MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax expression and caused a loss of mitochondrial membrane potential, and its effect was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced caspase activation, which was prevented by PD98059 and SB203580. The general caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO exerted the protective effect against the ciglitazone-induced cell death. The EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell death. Taken together, these findings suggest that the MAPK signaling pathways play an active role in mediating the ciglitazone-induced cell death of osteoblasts and function upstream of a mitochondria-dependent mechanism. These data may provide a novel insight into potential therapeutic strategies for treatment of osteoporosis.     

p38 mitogen-activated protein kinase contributes to angiotensin II-stimulated migration of rat aortic smooth muscle cells

In this study, we clarified the intracellular mechanism of angiotensin II (Ang II) in promoting migration in rat aortic smooth muscle cells (RASMCs). RASMC migration was measured with the Boyden chamber assay, and the result was confirmed with an aortic sprout assay. The activities of kinases were investigated by western blot analysis. Ang II enhanced RASMC migration, which was chemotaxis directed, and induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2), and heat shock protein 27 (Hsp27). Ang II-enhanced cell migration was inhibited by SB203580 (a p38 MAPK inhibitor) and piceatannol (a spleen tyrosine kinase inhibitor), but only partially by PD98059 (an ERK inhibitor) and PP2 (a Src inhibitor). The Ang II-stimulated phosphorylation of p38 MAPK and Hsp27 in RASMCs was inhibited by piceatannol and SB203580. The phosphorylation of ERK1/2 stimulated by Ang II was suppressed by PD98059, piceatannol, and PP2. Ang II increased the sprout outgrowth from aortic rings and this response was attenuated by pretreatment with SB203580, PD98059, PP2, or piceatannol. These results suggest that p38 MAPK contributes to the regulation of the Ang II-induced chemotactic migration of vascular smooth muscle cells, which is mediated by Hsp27 phosphorylation.     

八肽胆囊收缩素通过p38MAPK通路抑制LPS诱导的RAW264.7细胞IL-1β表达

目的研究八肽胆囊收缩素(CCK-8)对LPS诱导RAW264.7细胞IL-1β表达的影响及相关机制。方法用ELISA及RT-PCR法检测RAW264.7细胞IL-1βmRNA及蛋白表达;用Western blot检测RAW264.7细胞p38 MAPK的磷酸化水平。结果①LPS可时间依赖性的诱导RAW264.7细胞IL-1βmRNA及蛋白的表达,分别于刺激后3 h及6 h达到高峰;②10-10 mol.L-1 CCK-8对LPS诱导的RAW264.7细胞IL-1β表达无影响;10-8、10-6 mol.L-1CCK-8浓度依赖性地抑制了LPS诱导的RAW264.7细胞IL-1β表达;③10-10 mol.L-1 CCK-8未影响LPS诱导的p-p38MAPK水平,10-8、10-6 mol.L-1 CCK-8浓度依赖性地抑制了LPS诱导的p-p38 MAPK水平;④p38 MAPK特异性抑制剂SB203580可抑制LPS诱导的RAW264.7细胞IL-1β表达,与CCK-8共同作用后,抑制作用进一步加强。结论 CCK-8通过抑制p38 MAPK磷酸化而抑制了LPS诱导的RAW264.7细胞IL-1β表达,这可能是CCK-8发挥抗炎作用的信号转导机制之一。