JAK2/STAT3通路对大鼠脑出血周围组织VEGF165等的保护作用

The Neuroprotective Effect of VEGF165 on Cerebral Hemorrhage Through the JAK2/STAT3 Signaling Pathway

目的测定蛋白酪氨酸激酶2/信号转导和转录激活因子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(AG-490)对大鼠脑出血周围组织血管内皮生长因子165(VEGF165)、磷酸化蛋白酪氨酸激酶2(P-JAK2)、磷酸化信号转导和转录激活子3(P-STAT3)表达的影响,分析VEGF165与P-JAK2、P-STAT3的相关性,探讨VEGF165对大鼠脑出血后的神经保护作用是否由JAK2/STAT3信号通道介导。方法将健康雄性Sprague-Dawley(SD)大鼠75只随机分为假手术组、脑出血组和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6 h、24 h、48 h、72 h、7 d 5个亚组,比较各组大鼠进行神经功能缺损评分(NSS);免疫组化染色检测血肿周围VEGF165表达,采用Westernblotting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VEGF165、P-JAK2、P-STAT表达均高于假手术组(P<0.05),并于造模后48 h达高峰(P<0.05);AG-490组VEGF165、P-JAK2、P-STAT表达较脑出血组低(P<0.05);脑出血组VEGF165的表达与神经功能的缺损评分呈负相关(r=-0.511,P<0.05),VEGF165与P-JAK2、P-STAT3的表达呈正相关(r=0.562,P<0.05;r=0.479,P<0.05)。结论 VEGF165对大鼠脑出血后的神经保护作用可能是由JAK2/STAT3途径介导。

Objective To investigate the role of JAK2/STAT3 signal pathway and VEGF165 in neuroprotective effects of cerebral hemorrhage rats.Methods Seventy five healthy male Sprague Dawley(SD)rats were randomly divided into three groups:the sham operation,the cerebral hemorrhage group and AG-490 group.The autologous arterial blood was stereotaxically injected to right caudate nucleus to establish cerebral hemorrhage rat models,every group according to the different sacrificed time divided into 5 sub groups:6 h,24 h,48 h,72 h,7 d.The neurological deficit scores were evaluated by the Neurological Severity Scores(NSS).The expression of VEGF165 and P-JAK2,P-STAT3 in rat brain tissue around the hematoma were observed by immunostaining and western blotting.Results VEGF165,P-JAK2,P-STAT expression in cerebral hemorrhage group and AG-490 group were higher than that in normal group(P<0.05),which reached a peak at 48 h after modeling(P<0.05).VEGF165,P-JAK2,P-STAT expression in AG-490 group were lower than that in cerebral hemorrhage(P<0.05).NSS and VEGF165 expression were negatively correlated(r=0.511,P<0.05).VEGF165 expression was positively correlated with P-JAK2,P-STAT3 expression(r=0.562,P<0.05;r=0.479,P<0.05).Conclusion Neuroprotective effect of VEGF165 on cerebral hemorrhage may be mediated by JAK2/STAT3 pathway in rats.