JAK2/STAT3通路介导热休克蛋白70对脑出血的神经保护作用The neuroprotective effect of heat shock protein 70 through the JAK2/STAT3 signaling pathway in cerebral hemor-rhage
袁志俊;李小刚;何晓英;
摘要(Abstract):
目的观察蛋白酪氨酸激酶2/信号转导和转录激活因子3(janus kinase 2-signal transducer and activator of transcription 3,JAK2/STAT3)信号通路特异性拮抗剂α-氰基-(3,4-羟基)N-苄苯乙烯胺〔alpha cyano-(3-hydroxy)N-styrene benzyl amine,AG-490〕对脑出血大鼠脑组织热休克蛋白70(heat shock protein 70,HSP70)、磷酸化蛋白酪氨酸激酶2(phosphorylated janus kinase 2,P-JAK2)、磷酸化信号转导和转录激活因子3(phosphorylated signal transducer and activator of transcription 3,P-STAT3)表达的影响,并分析HSP70与PJAK2、P-STAT3的相关性,探讨JAK2/STAT3信号通路是否介导HSP70对大鼠脑出血后的神经保护作用。方法将健康雄性Sprague-Dawley(SD)大鼠100只随机分为正常组、假手术组、脑出血和AG-490组;采用大鼠自体血注入法建立脑出血模型;各组按造模成功后时间分为6h、24h、48h、72h、7d共5个亚组,对各组大鼠进行神经功能缺损评分(neurological severity scores,NSS);免疫组化染色检测血肿周围HSP70表达,采用Western blot检测大鼠血肿周围脑组织P-JAK2、P-STAT3的表达。结果脑出血组和AG-490组HSP70、P-JAK2、PSTAT表达均高于假手术组和正常组(P<0.05),并于造模后48h达高峰(P<0.05);AG-490组HSP70、PJAK2、P-STAT表达较脑出血组低(P<0.05);脑出血组HSP70表达与NSS评分呈负相关(r=-0.511,P<0.05),HSP70表达与P-JAK2、P-STAT3的表达呈正相关(r=0.790,P<0.05;r=0.447,P<0.05)。结论 JAK2/STAT3信号通路可能通过上调HSP70的表达进而对大鼠脑出血后起神经保护作用。
关键词(KeyWords): 脑出血;HSP70蛋白质类;janus激酶2;STAT3转录因子
基金项目(Foundation): 四川省卫生厅科研课题(110368)
作者(Author): 袁志俊;李小刚;何晓英;
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DOI:
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