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托法替尼对脑出血大鼠早期脑水肿的治疗效果及其作用机制
王晓宇,陈伟,陈兢,刘富均,赵杰祎
0
(四川大学华西医院神经外科)
摘要:
目的 探讨托法替尼对脑出血大鼠早期脑水肿的治疗效果及其作用机制。方法 SD大鼠制作脑出血模型,建模成功后,治疗组予腹腔注射药物托法替尼,对照组注射生理盐水。动态观察两组大鼠不同时间点的行为学评分,脑组织含水量,JAK2、p JAK2.STAT3和p STAT3的表达以及炎症因子的表达情况,并釆用统计学方法进行分析比较。结果 与对照组相比,治疗组大鼠的脑组织含水量在各个时间点上均较低(PV005);治疗组前肢上抬反射实验 (左侧)评分更高、向转角实验(右側)评分更低(P<0. 05)。两组大鼠血肿周围脑组织TNF a、IL 1(3. COX 2、IL 6、 p JAK2和p STATS表达均于术后逐渐增加,并于建模后3d达到高峰,随后逐渐下降;治疗组上述各指标表达于术后第 1、3、5天较对照组更低(PV0.05),在第7天表达无统计学差异(P>0.05)。结论 本研究结果表明托法替尼能减轻脑 出血大鼠早期脑水肿,具有脑组织保护作用;其可能的机制是托法替尼在大鼠脑出血后抑制JAK2 STAT3信号通路,降 低p JAK2、p STAT3和相关炎性因子表达。
关键词:  JAK STAT  脑出血  脑水肿  炎性因子  托法替尼
DOI:
基金项目:四川省科技厅科技支撑计划项目(2016FZ0U9)
Therapeutic effect and mechanism of tofacitinib on early ceaebral edema in rats with cerebral hemorrhage
WANG Xiaoyu,CHEN Wei,CHEN Jing,LIU Fujun,ZHAO Jieyi
(Department of Neurosurery , West China Hospital, Sichuan University)
Abstract:
Objective To investigate the effect and mechanism of tofacitinib on brain edema in rats with cerebral hemorrhage. Methods We made ICH model by SD rat right basal ganglia blood injection method. After success ? the treatment group was injected with tofacitinib and the control group was injected with saline in intraperitoneal. The behav ioral scores, brain water content, expression of JA.K2, p JAK2, ST AT 3 and p STATS, and expression of inflammatory factors at different time points were dynamically observed. Results Compared with the control group, the water content of brain tissue in the treatment group was lower at all time points (P<0.05 ), In the treatment group, the score of the left side was higher than that of the right side (P<0.05), The expression of TNF-a, IL-1 [3, COX-2, IL-6, P JAK2 and P STATS in the brain tissue around hematoma of the two groups increased gradually after operation, reached the peak 3 days after modeling, and then decreased gradually. The expression of the above indexes in the treatment group was lower than that in the control group on the 1st, 3rd and 5th day after operation (P<0.05) , and there was no statistical differ ence on the 7th day (P〉0.05). Conclusion The results of this study suggesting that tofacitinib can alleviate early brain edema in ICH rats and have brain tissue protection. The possible mechanism is that tofacitinib inhibits the JAK2 ST AT 3 signaling pathway after cerebral hemorrhage and reduces p JAK2, p STATS and related inflammatory factors expression
Key words:  JAK STAT  Cerebral hemorrhage  Brain edema  Inflammatory factors  Tofacitinib

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