虎杖苷调节JAK2/STAT3信号通路对高血压脑出血大鼠神经炎症的影响  

Effect of Polydatin on Neuroinflammation in Rats with Hypertensive Intracerebral Hemorrhage via Regulation of the JAK2/STAT3 Signaling Pathway

作　　者：许永杰 贾晓龙 王燕领 王晓丹 XU Yongjie;JIA Xiaolong;WANG Yanling(Handan First Hospital,Hebei Handan 056002,China)

机构地区：[1]河北省邯郸市第一医院CT室,河北邯郸056002 [2]河北省邯郸市中心医院彩超室,河北邯郸056001

出　　处：《河北医学》2024年第6期900-905,共6页Hebei Medicine

基　　金：河北省卫生健康委基金项目,(编号:20210215)。

摘　　要：目的:探讨虎杖苷调节JAK2/STAT3信号通路对高血压脑出血(HICH)大鼠神经炎症的影响。方法:Sprague-Dawley大鼠随机分为假手术组、HICH组、虎杖苷低、中、高剂量(虎杖苷-L、虎杖苷-M、虎杖苷-H)组(25mg/kg、50mg/kg、100mg/kg虎杖苷)、虎杖苷-H+JAK2/STAT3通路激活剂(Colivelin)(100mg/kg虎杖苷+1mg/kg Colivelin)组,10只/组,假手术组仅进行钝性分离双侧肾动脉以及注射生理盐水操作,其余各组通过银夹狭窄双侧肾动脉以及注射自体血建立HICH大鼠,随后进行相应药物或生理盐水干预,3d后进行改良神经功能缺损程度评分(mNSS)评分及脑水量检测;分离血清,ELISA检测白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α水平;分离脑组织,HE检测其病理变化;免疫荧光检测IL-10、IL-4表达;Western blot检测JAK2/STAT3信号通路相关蛋白表达。结果:与假手术组相比,HICH组mNSS评分、血清IL-1β、TNF-α水平、含水量、p-JAK2/JAK2、p-STAT3/STAT3表达显著增加,但IL-10、IL-4表达降低(P<0.05);与较HICH组相比,虎杖苷-L组、虎杖苷-M组、虎杖苷-H组mNSS评分、血清IL-1β、TNF-α水平、含水量、p-JAK2/JAK2、p-STAT3/STAT3表达显著降低,但IL-10、IL-4表达增加,不同浓度虎杖苷组有统计学差异(P<0.05);与虎杖苷-H组相比,虎杖苷-H+Colivelin组mNSS评分、血清IL-1β、TNF-α水平、含水量、p-JAK2/JAK2、p-STAT3/STAT3表达显著增加,但IL-10、IL-4表达降低(P<0.05)。结论:虎杖苷通过抑制JAK2/STAT3信号通路,降低HICH大鼠促炎因子水平,提高抗炎水平,减轻HICH大鼠病理损伤。Objective:To investigate the effect of polydatin on neuroinflammation in rats with hypertensive intracerebral hemorrhage(HICH)through the regulation of the JAK2/STAT3 signaling pathway.Methods:Sprague-Dawley rats were randomly divided into six groups:sham operation group,HICH group,and three polydatin dosage groups(low,medium,and high;Polydatin-L,Polydatin-M,Polydatin-H;25mg/kg,50mg/kg,100mg/kg respectively),and the Polydatin-H+JAK2/STAT3 pathway activator(Colivelin)group(100mg/kg Polydatin+1 mg/kg Colivelin),with 10 rats in each group.The sham operation group underwent blunt separation of bilateral renal arteries and injection of saline,while the other groups were induced with HICH by bilateral renal artery constriction using silver clips and autologous blood injection,followed by respective drug or saline interventions.Three days later,modified Neurological Severity Score(mNSS)and brain water content were measured.Serum was isolated for ELISA to detect levels of interleukin(IL)-1βand tumor necrosis factor(TNF)-α.Brain tissue was isolated for pathological changes observed by HE staining,IL-10 and IL-4 expression detected by immunofluorescence,and JAK2/STAT3 signaling pathway-related protein expression analyzed by Western blot.Results:Compared with the sham operation group,the HICH group showed significantly increased mNSS score,serum IL-1β,TNF-αlevels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but decreased IL-10 and IL-4 expressions(P<0.05).Compared with the HICH group,the Polydatin-L,Polydatin-M,and Polydatin-H groups had significantly decreased mNSS scores,serum IL-1β,TNF-αlevels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but increased IL-10 and IL-4 expressions,with statistically significant differences among the different concentrations of polydatin(P<0.05).Compared with the Polydatin-H group,the Polydatin-H+Colivelin group had significantly increased mNSS score,serum IL-1β,TNF-αlevels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but decreased I

关 键 词：虎杖苷 JAK2/STAT3信号通路 高血压脑出血 

分 类 号：R285.5[医药卫生—中药学]