Objective To investigate the effect of hirudin on janus kinase 2 / signal transducer and activator of transcription 3 (JAK2 / STAT3)signaling pathway in rats with intracerebral hemorrhage. Methods A total of 216 healthy male Wistar rats were divided into sham operation group,model group, and hirudin group (n =72 in each group)using random digit table. The model of cerebral hemorrhage was induced by injecting autologous arterial blood into the caudate nucleus,and the equal volume isotonic saline was used instead of autologous arterial blood in the sham operation group. Hirudin were injected at 6,24, 72,and 120 h,respectively in the hirudin group,while the sham operation group and the model group were injected with isotonic saline during same period. Neurobehavioral scores,brain water content and brain coefficients of the 3 groups at the different time points were compared. The changes of brain cell apoptosis were detected with annexin V-fluorescein isothiocyanate/ propidium iodide double staining flow cytometry. The expression levels of phosphorylated JAK2 (p-JAK2)and phosphorylated STAT3 (p-STAT3)in brain tissue were detected with Western blot. Results (1)Compared with the sham operation group at same time period,neurobehavioral score,brain water content,brain coefficients,brain cell apoptosis rate,and the expression levels of p-JAK2 and p-STAT3 were increased significantly in the rats of the model group. The differences between the two groups were statistically significant (all P < 0. 05). Compared with the model group at same time period,neurobehavioral score,brain water content,brain coefficients,and brain cell apoptosis rate were decreased significantly in the rats of the hirudin group. The differences between the two groups were statistically significant (all P <0. 05). (2)At 6,24,72,and 120 h after modeling,the expression levels of p-JAK2 were 0. 632 ±0. 036,0. 783 ± 0. 045,1. 250 ± 0. 071,and 1. 006 ± 0. 052,respectively,and those of p-STAT3 were 0. 155 ±0. 005,0. 193 ±0. 006,0. 379 ±0. 012,and 0. 317 ± 0. 010,respectively in model group. The expression levels of p-JAK2 were 0. 267 ± 0. 014,0. 248 ± 0. 013,0. 329 ± 0. 018,and 0. 283 ±0. 016,respectively,and those of p-STAT3 were 0. 139 ± 0. 004,0. 081 ± 0. 001,0. 283 ± 0. 009, and 0. 174 ± 0. 005,respectively in the hirudin group. The expression levels of p-JAK2 and p-STAT3 in hirudin group were lower than those in the model group. There were significant differences between the two groups (all P < 0. 05). Conclusion Hirudin can reduce apoptosis of brain cells after intracerebral hemorrhage in rats,its protective mechanism may be associated with the inhibition of JAK2 / STAT3 signaling pathway.%目的 探讨水蛭素对脑出血大鼠脑组织蛋白酪氨酸激酶2/信号转导和转录激活因子3(JAK2/STAT3)信号通路的影响.方法 采用随机数字表法,将216只健康雄性Wistar大鼠分为假手术组、模型组和水蛭素组,每组72只.将大鼠自体动脉血注入尾状核建立脑出血模型,假手术组以等量等渗盐水代替自体动脉血.水蛭素组分别于模型建立后6、24、72、120 h注入水蛭素,假手术组和模型组则于同时点给予等量等渗盐水.对不同时点时3组脑出血大鼠神经行为学评分、脑含水量及脑系数进行比较;采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染流式细胞仪检测脑细胞凋亡的变化;蛋白质印迹法检测脑组织磷酸化JAK2(p-JAK2)及磷酸化STAT3(p-STAT3)的表达.结果 (1)与同时点假手术组比较,模型组大鼠神经行为学评分、脑含水量、脑系数、脑细胞凋亡率及p-JAK2和p-STAT3的表达均明显升高,组间差异均有统计学意义(均P<0.05);与同时点模型组比较,水蛭素组大鼠神经行为学评分、脑含水量、脑系数、脑细胞凋亡率均明显降低,组间差异均有统计学意义(均P<0.05).(2)造模后6、24、72、120 h,模型组p-JAK2分别为0.632±0.036、0.783±0.045、1.250±0.071、1.006±0.052,p-STAT3分别为0.155±0.005、0.193±0.006、0.379±0.012、0.317±0.010;水蛭素组p-JAK2分别为0.267±0.014、0.248±0.013、0.329±0.018、0.283±0.016,p-STAT3分别为0.139±0.004、0.081±0.001、0.283±0.009、0.174±0.005.水蛭素组p-JAK2和p-STAT3的表达均低于模型组,组间差异均有统计学意义(均P<0.05).结论 水蛭素可降低脑出血大鼠脑细胞凋亡,其保护机制可能与抑制JAK2/STAT3信号通路有关.
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