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

Therapeutic effect and mechanism of tofacitinib on early ceaebral edema in rats with cerebral hemorrhage

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,并采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(P<005);治疗组前肢上抬反射实验(左侧)评分更高、向转角实验(右侧)评分更低(P<0.05)。两组大鼠血肿周围脑组织TNF-α、IL-1β、COX-2、IL-6、p-JAK2和p-STAT3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(P<0.05),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。

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 behavioral scores,brain water content,expression of JAK2,p-JAK2,STAT3 and p-STAT3,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 TNFα,IL 1β,COX 2,IL 6,P JAK2 and P STAT3 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 difference 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-STAT3 signaling pathway after cerebral hemorrhage and reduces p-JAK2,p-STAT3 and related inflammatory factors expression.