JAK2/STAT3信号通路参与AngⅡ诱导的小鼠血管平滑肌细胞增殖及芦可替尼的干预作用  

JAK2/STAT3 signaling pathway is involved in promoting the proliferation of vascular smooth muscle cell induced by AngⅡand intervention of Ruxolitinib

作　　者：宋鸿涛[1] 崔媛 张莉莉[3] 曹光[4] 李琳 李刚 贾新菊[6] SONG Hong-tao;CUI Yuan;ZHANG Li-li;CAGuang;LI Lin;LI Gang;JIA Xin-ju(Department of Vascular Surgery,The Second Hospital of Shijiazhuang,Hebei 050001,China)

机构地区：[1]石家庄市第二医院周围血管外科,河北050051 [2]河北省中医药科学院附属医院 [3]石家庄市第二医院内分泌科 [4]石家庄市第二医院骨科 [5]天津市蓟州区疾病预防控制中心 [6]河北医科大学第一医院内分泌科

出　　处：《医学动物防制》2022年第7期680-683,687,共5页Journal of Medical Pest Control

基　　金：河北省医学科学研究重点课题计划(20201340)。

摘　　要：目的探讨JAK2/STAT3信号通路在血管紧张素Ⅱ(AngⅡ)诱导血管平滑肌细胞(vascular smooth muscle cell,VSMC)增殖中的作用机制及芦可替尼(Ruxolitinib,Ruxo)的作用,为Ruxolitinib治疗血管平滑肌细胞增殖性疾病提供科学依据。方法用AngⅡ处理体外培养的VSMC,在给予血管紧张素Ⅱ-1型受体(AngⅡtype 1 receptor,AT1R)抑制剂、血管紧张素Ⅱ-2型受体(AngⅡtype 2 receptor,AT2R)抑制剂、JAK2/STAT3信号通路抑制剂及Ruxolitinib处理后,MTS、细胞计数检测AngⅡ诱导的VSMC增殖的影响,实时荧光定量PCR(real time fluorescent quantitative PCR,RT-PCR)检测VSMC增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)mRNA表达的影响,蛋白质印迹法(Western blotting,WB)检测p-STAT3、STAT3蛋白水平。结果MTS结果显示,Losartan、AG490和Ruxolitinib能显著抑制AngⅡ诱导的VSMC增殖(t=3.42、6.22、11.35,P<0.05),细胞计数结果一致(t=7.61、7.74、9.227,P<0.05),差异均有统计学意义。RT-PCR结果显示,Losartan和AG490显著抑制AngⅡ诱导的VSMC中PCNA的mRNA表达(t=7.248、25.720,P<0.01),差异均有统计学意义。WB结果显示,Losartan、AG490和Ruxolitinib显著抑制AngⅡ诱导的VSMC中STAT3的活化(t=12.970、11.770、9.227,P<0.01),差异均有统计学意义。结论AngⅡ通过促进JAK2/STAT3的活化从而诱导VSMC增殖,同时Ruxolitinib可抑制VSMC增殖,该作用机制可能与JAK2/STAT3通路活化的抑制有关。Objective To investigate the role of the JAK2/STAT3 signaling pathway in the proliferation of vascular smooth muscle cell(VSMC)induced by angiotensin II(AngⅡ)and the role of Ruxolitinib,to provide of the scientific basis for Ruxolitinib in the treatment of VSMC proliferative cell diseases.Methods VSMC cultured in vitro were treated with AngⅡfollowed by angiotensin II type 1 receptor(AngⅡtype 1 receptor,AT1 R)inhibitor,angiotensin II type 2 receptor(AngⅡtype 2 receptor,AT2 R)inhibitor,JAK2/STAT3 signaling pathway inhibitor and Ruxolitinib after treatment MTS,cell count to detect the effecte of AngⅡinduced VSMC proliferation.The expression of proliferating cell nuclear antigen(PCNA)mRNA in VSMC was detected by real time fluorescent quantitative PCR(RT-PCR),and protein blotting(Western blotting,WB)detection of p-STAT3 and STAT3 protein levels.Results The MTS results showed that Losartan,AG490 and Ruxolitinib significantly inhibited the proliferation of VSMC induced by AngⅡ(t=3.42,6.22,11.35,P<0.05)and the cell count result were consistent(t=7.61,7.74,9.227,P<0.05),all differences were statistically significant.RT-PCR results showed that Losartan and AG490 significantly inhibited the expression of PCNA mRNA in VSMC induced by AngⅡ(t=7.248,25.720,P<0.01),the differences were all statistically significant.WB results showed that Losartan,AG490 and Ruxolitinib significantly inhibited the activation of STAT3 in VSMC(t=12.970,11.770,9.227,P<0.01),all the differences were statistically significant.Conclusion AngⅡinduces VSMC proliferation by promoting JAK2/STAT3 activation,while ruxolitinib inhibits VSMC proliferation,and this mechanism of action may be related to the inhibition of JAK2/STAT3 pathway activation.

关 键 词：血管紧张素Ⅱ JAK2/STAT3细胞信号通路 血管平滑肌细胞 细胞增殖 芦可替尼 

分 类 号：R732[医药卫生—肿瘤] R979.1[医药卫生—临床医学]