促血小板生成素对大鼠局灶性脑缺血-再灌注损伤后JAK2/STAT3信号通路的影响  

Influence of Thrombopoietin on JAK2 / STAT3 Signal Transduction Pathway in Focal Cerebral Ischemia-Reperfusion Injury of Rats

作　　者：邹成林[1] 陈维钧[1] 孙晓顺[1] 方璟[1] 涂军[1] 赵亚洲[1] 

机构地区：[1]湖北省荆州市第二人民医院内一科,荆州434000

出　　处：《医药导报》2015年第8期1019-1023,共5页Herald of Medicine

摘　　要：目的探讨促血小板生成素(TPO)对大鼠脑缺血-再灌注损伤的保护作用及相关信号转导通路机制。方法采用大脑中动脉线栓法制作大鼠局灶性脑缺血-再灌注损伤模型。将80只雄性SD大鼠随机分为4组,分别为假手术组、模型对照组、TPO组、TPO+蛋白质酪氨酸激酶抑制药(AG490)组。于缺血-再灌注前30 min,TPO组给予5μg·kg-1TPO腹腔注射,TPO+AG490组于缺血-再灌注前30 min先腹腔内注射5μg·kg-1TPO,再给予8μg·kg-1AG490腹腔注射,模型对照组给予等剂量0.9%氯化钠溶液。再灌注6,12,24,48 h后处死取脑组织、切片,进行苏木精-伊红染色、免疫组化染色、Western blotting和细胞凋亡检测。结果与模型对照组比较,缺血-再灌注24 h后TPO组细胞凋亡数减少[(67.50±9.37)比(40.20±7.47)个],Bcl-2、蛋白质酪氨酸激酶2(JAK2)及信号转导和转录激活因子3(STAT3)蛋白表达水平升高,分别为(35.40±7.39)比(78.70±9.75),(35.68±6.75)比(62.35±7.53),(25.40±9.45)比(55.36±9.69),均差异有统计学意义(P<0.05)。与TPO组比较,TPO+AG490组Bcl-2、JAK2及STAT3蛋白表达水平降低,分别为(78.70±9.75)比(55.40±9.35),(62.35±7.53)比(40.68±5.89),(55.36±9.69)比(30.40±9.39),细胞凋亡数增多[(40.20±7.47)比(55.23±7.65)个],均差异有统计学意义(P<0.05)。结论 TPO可降低缺血-再灌注所诱导的细胞凋亡,其机制可能与激活JAK2/STAT3信号转导通路上调Bcl-2有关。Objective To investigate protective effects of thrombopoietin （TPO） on cerebral model control in rats and associated signal transduction pathway. Methods Thread embolism was performed to generate cerebral ischemia-reperfusion rat model.Eighty male SD rats were randomly divided into sham operation group, model control group, TPO group, TPO and Janus kinase inhibitor （ AG490 ） group. Before 30 min of ischemia-reperfusion, TPO group was given TPO （ 5 μg·kg^-1 ） by intraperitoneal injection, TPO ＋ AG490 group was given TPO （5 μg·kg^-1 ） before 30 min of ischemia reperfusion, then given AG490 （ 8μg·kg^-1 ）, and model control group were given the same dose of 0.9% sodium chloride solution.The observation time points were 6, 12, 24, and 48 h after ischemia reperfusion. Immunohistochemical staining and Western blotting were used to measure the protein levels of Bcl-2, JAK2 and signal transducer ＆ activator of transcription （STAT3）.TdT-mediated dUTP nick end labeling （TUNEL） was used to detect apoptosis. Results Compared with model control group, the number of apoptotic cells were significantly reduced [ （67.50±9.37） vs. （40.20±7.47） ] , the expression levels of Bcl-2, JAK2 and STAT3 protein were significantly increased [ （35.40±7.39） vs.（78.70±9.75） ; （35.68±6.75） vs. （62.35±7.53） ; （25.40±9.45） vs. （ 55.36±9.69）, respectively] 24 h after ischeia reperfusion in the TPO group （all P〈0.05）.Compared with the TPO group, the Bel-2, JAK2 and STAT3 protein levels were significantly decreased in TPO and AG490 group [ （78.70±9.75） vs. （55.40±9.35）; （62.35±7.53） vs.（40.68±5.89） ; （55.36±9.69） vs. （30.40±9.39）, respetively] , and the number of apoptotic cells was significantly increased [ （40.20±7.47） vs.（55.23±7.65） ] （all P〈0.05）. Conclusion TPO can inhibit eell apoptosis after isehemia-reperfusion injury, the mechanism might be related to the activation of JAK2/STAT3 signal transduetion pathway throug

关 键 词：促血小板生成素 大鼠 损伤 缺血-再灌注 细胞凋亡 蛋白质酪氨酸激酶2与转导激活因子3 Bcl-2 

分 类 号：R973.6[医药卫生—药品] R965[医药卫生—药学]