目的检测细胞因子信号转导抑制剂3(SOCS3)在大鼠颈外静脉颈总动脉移植物和体外培养的动脉血管平滑肌细胞增殖模型中的表达,探讨其在静脉移植物再狭窄病理过程中的可能作用及机制。方法体内实验分两组,将36只雄性SD大鼠随机分成实验组和...目的检测细胞因子信号转导抑制剂3(SOCS3)在大鼠颈外静脉颈总动脉移植物和体外培养的动脉血管平滑肌细胞增殖模型中的表达,探讨其在静脉移植物再狭窄病理过程中的可能作用及机制。方法体内实验分两组,将36只雄性SD大鼠随机分成实验组和对照组,每组18只。实验组采用标准显微外科技术行颈外静脉颈总动脉翻转端吻合,对照组行假手术,分别于术后第1、3、7天取出移植静脉。体外培养的大鼠血管平滑肌细胞用碱性成纤维细胞生长因子(b FGF)刺激,再用大鼠SOCS3基因重组腺病毒(p Yr Ad-r SOCS3)、对照病毒p Yr Ad-GFP转染,体外实验分四组:对照组,b FGF组,b FGF+p Yr Ad-GFP组,b FGF+p Yr Ad-r SOCS3组。应用Real time-PCR和Western boltting检测白介素6(IL-6)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)、信号转导与转录激活因子(STAT3)、磷酸化的信号转导与转录激活因子(PSTAT3)、SOCS3 m RNA和蛋白表达水平。结果体内实验表明,与对照组比较,实验组静脉移植物中IL-6[(3.60±0.51)比(1.00±0.00);(1.52±0.37)比(0.35±0.05)]、MCP-1[(2.08±0.38)比(1.00±0.00);(1.90±0.31)比(0.85±0.17)]、TNF-α[(4.86±0.74)比(1.00±0.00);(1.66±0.30)比(0.29±0.07)]、IL-1β[(2.73±0.52)比(1.00±0.00);(0.74±0.17)比(0.19±0.04)]、ICAM-1[(1.97±0.35)比(1.00±0.00);(1.02±0.39)比(0.21±0.02)]、SOCS3[(1.93±0.38)比(1.00±0.00);(0.82±0.18)比(0.42±0.12)]m RNA和蛋白表达水平以及STAT3[(1.50±0.36)比(0.21±0.05)]、P-STAT3[(1.54±0.39)比(0.37±0.10)]蛋白表达水平均在1周内明显升高(P<0.05或P<0.01)。体外实验结果表明,与对照组比较,b FGF组中上述指标m RNA和蛋白表达明显上调(P<0.05或P<0.01);与b FGF组比较,b FGF+p Yr Ad-r SOCS3组中SOCS3 m RNA和蛋白[(5.47±1.03)比(1.37±0.24);(1.79±0.38)比(1.28±0.32)]表达进一步上调(P<0.01、P<0.05),而IL-6[(1.28±0.25)比(1.57±0.31);(1.68±0.39)比(2.36±0.48)]、MCP-1[(1.17±0.23)比(2.08±0.37);(1.25±0.21)比(1.66±0.43)]、TNF-α[(1.37±0.23)比(3.06±0.52);(1.20±0.24)比(1.54±0.31)]、IL-1β[(1.48±0.21)比(1.71±0.19);(1.00±0.24)比(1.49±0.35)]、ICAM-1[(1.34±0.21)比(2.10±0.27);(0.99±0.21)比(1.41±0.32)]m RNA和蛋白表达水平以及STAT3[(0.77±0.13)比(1.30±0.27)]、P-STAT3[(1.18±0.36)比(1.74±0.36)]蛋白表达明显下调(P<0.05或P<0.01)。结论 SOCS3在静脉移植物病变的早期病理炎性反应中,可能通过抑制其下游信号通路的关键转录因子STAT3的激活及其磷酸化而发挥负向调节作用,可为冠状动脉旁路移植术后静脉移植物再狭窄的理论研究和临床防治提供一种新思路和新靶点。展开更多
信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)是一种细胞内信号转导因子,在细胞的生长、分化、凋亡和免疫应答等方面发挥重要作用。辅助性T细胞17(T helper cell 17,Th17)的异常活化与多种自身...信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)是一种细胞内信号转导因子,在细胞的生长、分化、凋亡和免疫应答等方面发挥重要作用。辅助性T细胞17(T helper cell 17,Th17)的异常活化与多种自身免疫性疾病的发生和发展密切相关。STAT3通过诱导Th17细胞过度增殖、异常分化并影响淋巴细胞浸润外分泌腺等机制参与干燥综合征(Sjogren syndrome)的疾病进展,因此阻断STAT3信号转导通路是治疗干燥综合征的潜在药物治疗靶点。本文综述了STAT3通过调节Th17细胞参与干燥综合征发病及进展的研究,并聚焦于STAT3信号通路抑制剂的最新研究进展,为该靶点在干燥综合征的治疗药物相关研究提供依据。展开更多
AIM:The study investigated if EGF signaling inhibitors, EGF antibody and tyrphostin 51 (a tyrosine kinase inhibitor),mediated the action of EGF on apoptosis and the expression of EGF receptors and p21 (a cyclin-depend...AIM:The study investigated if EGF signaling inhibitors, EGF antibody and tyrphostin 51 (a tyrosine kinase inhibitor),mediated the action of EGF on apoptosis and the expression of EGF receptors and p21 (a cyclin-dependent kinase inhibitor) of human colorectal cancer cells.METHODS: Human colorectal adenocarcinoma cells (SW480) were incubated with 0.6mL/L dimethyl sulfoxide (DMSO, the control group), 225ng/mL (37.5nmol/L) EGF in 0.6mL/L DMSO, 225ng/mL EGF+2.5μg/mL (17 nmol/L)EGF antibody in 0.6mL/L DMSO, or 225ng/mL EGF+215ng/mL (0.8μmol/L) tyrphostin 51 in 0.6mL/L DMSO.RESULTS:After 48h incubation, the levels of EGF in medium significantly increased (P<0.05) in the EGF-treated groups.The numbers of apoptotic cells were significantly fewer (P<0.05) in the EGF+EGF antibody and EGF+tyrphostin 51 groups than those in the control and EGF groups after 12h treatments. The expression of phosphorylated EGF receptors in the EGF, EGF+EGF antibody,and EGF+tyrphostin 51 groups was 176.8%, 62.4%, and 138.1% of the control group, respectively. The expression of p21 protein in the EGF, EGF+EGF antibody, and EGF+tyrphostin 51 groups was 115.7%, 4.8%, and 61.5% of the control group, respectively.CONCLUSION:The data suggest that EGF antibody and tyrphostin 51 can inhibit the action of EGF on apoptosis in human colorectal cancer cells through down-regulation of EGF receptor and p21 expression.展开更多
文摘目的检测细胞因子信号转导抑制剂3(SOCS3)在大鼠颈外静脉颈总动脉移植物和体外培养的动脉血管平滑肌细胞增殖模型中的表达,探讨其在静脉移植物再狭窄病理过程中的可能作用及机制。方法体内实验分两组,将36只雄性SD大鼠随机分成实验组和对照组,每组18只。实验组采用标准显微外科技术行颈外静脉颈总动脉翻转端吻合,对照组行假手术,分别于术后第1、3、7天取出移植静脉。体外培养的大鼠血管平滑肌细胞用碱性成纤维细胞生长因子(b FGF)刺激,再用大鼠SOCS3基因重组腺病毒(p Yr Ad-r SOCS3)、对照病毒p Yr Ad-GFP转染,体外实验分四组:对照组,b FGF组,b FGF+p Yr Ad-GFP组,b FGF+p Yr Ad-r SOCS3组。应用Real time-PCR和Western boltting检测白介素6(IL-6)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)、信号转导与转录激活因子(STAT3)、磷酸化的信号转导与转录激活因子(PSTAT3)、SOCS3 m RNA和蛋白表达水平。结果体内实验表明,与对照组比较,实验组静脉移植物中IL-6[(3.60±0.51)比(1.00±0.00);(1.52±0.37)比(0.35±0.05)]、MCP-1[(2.08±0.38)比(1.00±0.00);(1.90±0.31)比(0.85±0.17)]、TNF-α[(4.86±0.74)比(1.00±0.00);(1.66±0.30)比(0.29±0.07)]、IL-1β[(2.73±0.52)比(1.00±0.00);(0.74±0.17)比(0.19±0.04)]、ICAM-1[(1.97±0.35)比(1.00±0.00);(1.02±0.39)比(0.21±0.02)]、SOCS3[(1.93±0.38)比(1.00±0.00);(0.82±0.18)比(0.42±0.12)]m RNA和蛋白表达水平以及STAT3[(1.50±0.36)比(0.21±0.05)]、P-STAT3[(1.54±0.39)比(0.37±0.10)]蛋白表达水平均在1周内明显升高(P<0.05或P<0.01)。体外实验结果表明,与对照组比较,b FGF组中上述指标m RNA和蛋白表达明显上调(P<0.05或P<0.01);与b FGF组比较,b FGF+p Yr Ad-r SOCS3组中SOCS3 m RNA和蛋白[(5.47±1.03)比(1.37±0.24);(1.79±0.38)比(1.28±0.32)]表达进一步上调(P<0.01、P<0.05),而IL-6[(1.28±0.25)比(1.57±0.31);(1.68±0.39)比(2.36±0.48)]、MCP-1[(1.17±0.23)比(2.08±0.37);(1.25±0.21)比(1.66±0.43)]、TNF-α[(1.37±0.23)比(3.06±0.52);(1.20±0.24)比(1.54±0.31)]、IL-1β[(1.48±0.21)比(1.71±0.19);(1.00±0.24)比(1.49±0.35)]、ICAM-1[(1.34±0.21)比(2.10±0.27);(0.99±0.21)比(1.41±0.32)]m RNA和蛋白表达水平以及STAT3[(0.77±0.13)比(1.30±0.27)]、P-STAT3[(1.18±0.36)比(1.74±0.36)]蛋白表达明显下调(P<0.05或P<0.01)。结论 SOCS3在静脉移植物病变的早期病理炎性反应中,可能通过抑制其下游信号通路的关键转录因子STAT3的激活及其磷酸化而发挥负向调节作用,可为冠状动脉旁路移植术后静脉移植物再狭窄的理论研究和临床防治提供一种新思路和新靶点。
文摘AIM:The study investigated if EGF signaling inhibitors, EGF antibody and tyrphostin 51 (a tyrosine kinase inhibitor),mediated the action of EGF on apoptosis and the expression of EGF receptors and p21 (a cyclin-dependent kinase inhibitor) of human colorectal cancer cells.METHODS: Human colorectal adenocarcinoma cells (SW480) were incubated with 0.6mL/L dimethyl sulfoxide (DMSO, the control group), 225ng/mL (37.5nmol/L) EGF in 0.6mL/L DMSO, 225ng/mL EGF+2.5μg/mL (17 nmol/L)EGF antibody in 0.6mL/L DMSO, or 225ng/mL EGF+215ng/mL (0.8μmol/L) tyrphostin 51 in 0.6mL/L DMSO.RESULTS:After 48h incubation, the levels of EGF in medium significantly increased (P<0.05) in the EGF-treated groups.The numbers of apoptotic cells were significantly fewer (P<0.05) in the EGF+EGF antibody and EGF+tyrphostin 51 groups than those in the control and EGF groups after 12h treatments. The expression of phosphorylated EGF receptors in the EGF, EGF+EGF antibody,and EGF+tyrphostin 51 groups was 176.8%, 62.4%, and 138.1% of the control group, respectively. The expression of p21 protein in the EGF, EGF+EGF antibody, and EGF+tyrphostin 51 groups was 115.7%, 4.8%, and 61.5% of the control group, respectively.CONCLUSION:The data suggest that EGF antibody and tyrphostin 51 can inhibit the action of EGF on apoptosis in human colorectal cancer cells through down-regulation of EGF receptor and p21 expression.
