JAK-STAT信号通路在激素性股骨头坏死的意义△

Significance of JAKSTAT signaling pathway in steroidinduced osteonecrosis of femoral head

摘要:

[目的] 探讨Janus 激酶-信号转导和转录激活因子信号通路（Janus kinase-signal transducer and activator of transcrip-tion signaling pathway, JAK-STAT signaling pathway） 与激素性股骨头坏死发生机制之间的关联。[方法] 体内试验，36 只Sprague-Dawley（SD） 大鼠按随机分为三组，每组12 只，分别为空白对照组、模型组和干预组，给予相应药物处理，行股骨头HE 染色和TUNEL 染色。体外试验，自幼鼠颅骨分离成骨细胞，分为同体内试验相同的三组，给予相应体外处理，检测ALP 和JAK-STAT 通路蛋白p-JAK2、p-STAT3 蛋白表达水平。[结果] 体内试验，HE 染色骨空隐窝率由高至低依次为：模型组＞干预组＞对照组，差异有统计学意义[(38.9±1.3)% vs (18.9±0.9)% vs (3.2±0.6)%, P＜0.001]；TUNEL 染色细胞凋亡率依次为：模型组＞干预组＞对照组，差异有统计学意义[(42.2±2.7)% vs (16.1±1.3)% vs (6.2±1.1) %, P＜0.001]。体外试验，TUNEL 染色细胞凋亡率由高至低依次为：模型组＞干预组＞对照组，差异有统计学意义[(42.3±3.5)% vs (18.2±1.6)% vs (10.2±1.3)%, P＜0.001]；ALP 由低至高依次为：模型组＜干预组＜对照组，差异有统计学意义[(53.6±7.7) IU vs (79.2±6.5) IU vs (92.4±4.4) IU, P=0.037]。此外，模型组JAKSTAT相关标志蛋白表达均显著高于对照组和干预组，p-JAK2 [(1.6±0.2), (1.0±0.1), (1.3±0.3), P＜0.05]、p-STAT [(1.4±0.2), (1.0±0.1),(1.2±0.3), P＜0.05]，差异具有统计学意义。[结论] JAK-STAT 信号通路特异性抑制剂AG490 可抑制激素引发细胞凋亡，其机理可能与抑制p-JAK2 和p-STAT 蛋白表达有关。

Abstract:

[Objective] To investigate the relationship of the Janus kinase-signal transducer and activator of transcription (JAK-STAT)signaling pathway with the pathogenesis of steroid-induced osteonecrosis of femoral head. [Methods] In vivo experiment, 36 Sprague-Daw-ley (SD) rats were randomly divided into three groups with 12 animals in each group, including the blank control group, model group and in-tervention group, which were treated with corresponding drugs respectively. The femoral head was harvest for HE and TUNEL staining 28days later. In vitro test, osteoblasts were separated from the skull of a young rat and divided into three groups as in vivo test. After correspond-ing treatments were given in vitro, the expression levels of ALP and JAK-STAT pathway related protein, such as JAK2 and p-STAT3, wereassessed. [Results] In vivo test, the rates of empty bone crypts revealed by HE stain was ranked up-down as follows: the model group ＞ theintervention group ＞ the control group, with a statistically significant difference [(38.9±1.3)% vs (18.9±0.9)% vs (3.2±0.6)%, P＜0.001], like-ly, the apoptosis rates showed by TUNEL stain was of the model group ＞ the intervention group ＞ the control group, with a statistically signifi-cant different [(42.2±2.7)% vs (16.1±1.3)% vs (6.2 ±1.1)%, P＜0.001]. In vitro test, apoptosis rate by TUNEL staining was ranked as: the mod-el group ＞ the intervention group ＞ the control group and the difference was statistically significant [(42.3±3.5)% vs (18.2±1.6)% vs (10.2±1.3)%, P＜0.001], whereas the ALP activity was ranked from low to high as: the model group ＜ the intervention group ＜ the control group witha statistically significant difference [(53.6±7.7) IU vs (79.2±6.5) IU vs (92.4±4.4) IU, P=0.037]. In addition, JAK-STAT-related marker pro-tein expression in model group was significantly higher than that in the control group and the intervention group, including p-JAK2 [(1.6±0.2) vs (1.0±0.1) vs (1.3±0.3), P＜0.05] and p-STAT [(1.4± 0.2) vs (1.0±0.1) vs (1.2±0.3), P＜0.05]. [Conclusion] The JAK-STAT signalingpathway specific inhibitor AG490 does inhibit steroid-induced cell apoptosis, its mechanism may be related to the inhibition of p-JAK2 andp-STAT protein expression.