协和医学杂志
協和醫學雜誌
협화의학잡지
MEDICAL JOURNAL OF PEKING UNION MEDICAL COLLEGE HOSPITAL
2014年
2期
142-147
,共6页
薛照静%申乐%王之遥%黄宇光
薛照靜%申樂%王之遙%黃宇光
설조정%신악%왕지요%황우광
神经病理性疼痛%JAK/STAT通路%WP1066%双侧坐骨神经结扎
神經病理性疼痛%JAK/STAT通路%WP1066%雙側坐骨神經結扎
신경병이성동통%JAK/STAT통로%WP1066%쌍측좌골신경결찰
neuropathic pain%JAK/STAT signaling pathway%WP1066%bilateral chronic sciatic nerve constriction injury
目的：观察Janus激酶2（Janus kinase 2， JAK2）/信号转导和转录激活子3（signal transducers and activators of transcription 3， STAT3）通路抑制剂WP1066对神经病理性疼痛的影响。方法12只体重180～200 g雌性SD大鼠用随机数字表法分为WP1066组及对照组（n＝6），均行双侧坐骨神经结扎手术，两组于术前1 d、术前及术后第3、5天分别经鞘内注射容量为10μl的WP1066（10 mmol/L溶于二甲基亚砜）或二甲基亚砜，于术前及术后第3、5、7、10、14天进行动物行为学检测，观察大鼠对机械、热及丙酮冷刺激的反应。术后第14天处死大鼠，于L4～L6腰膨大脊髓背角处取材，使用RT-PCR及Western blot检测STAT3、细胞因子信号抑制因子3（ suppressor of cytokine signaling 3， SOCS3）、 JAK2 mRNA及蛋白水平。结果大鼠机械缩足反射阈值、热刺激缩足反射潜伏期和冷痛阈值分别从第3、5、5天开始， WP1066组较对照组明显升高，差异具有统计学意义（P＜0.05）。与对照组相比， WP1066组STAT3、 SOCS3、 JAK2 mRNA表达均明显降低（ P＜0.05）； WP1066组磷酸化STAT3、 SOCS3、 JAK2蛋白水平均亦明显降低（ P＜0.05）。结论 WP1066可明显改善大鼠神经病理性疼痛，可能为治疗神经病理性疼痛提供新的靶点。
目的：觀察Janus激酶2（Janus kinase 2， JAK2）/信號轉導和轉錄激活子3（signal transducers and activators of transcription 3， STAT3）通路抑製劑WP1066對神經病理性疼痛的影響。方法12隻體重180～200 g雌性SD大鼠用隨機數字錶法分為WP1066組及對照組（n＝6），均行雙側坐骨神經結扎手術，兩組于術前1 d、術前及術後第3、5天分彆經鞘內註射容量為10μl的WP1066（10 mmol/L溶于二甲基亞砜）或二甲基亞砜，于術前及術後第3、5、7、10、14天進行動物行為學檢測，觀察大鼠對機械、熱及丙酮冷刺激的反應。術後第14天處死大鼠，于L4～L6腰膨大脊髓揹角處取材，使用RT-PCR及Western blot檢測STAT3、細胞因子信號抑製因子3（ suppressor of cytokine signaling 3， SOCS3）、 JAK2 mRNA及蛋白水平。結果大鼠機械縮足反射閾值、熱刺激縮足反射潛伏期和冷痛閾值分彆從第3、5、5天開始， WP1066組較對照組明顯升高，差異具有統計學意義（P＜0.05）。與對照組相比， WP1066組STAT3、 SOCS3、 JAK2 mRNA錶達均明顯降低（ P＜0.05）； WP1066組燐痠化STAT3、 SOCS3、 JAK2蛋白水平均亦明顯降低（ P＜0.05）。結論 WP1066可明顯改善大鼠神經病理性疼痛，可能為治療神經病理性疼痛提供新的靶點。
목적：관찰Janus격매2（Janus kinase 2， JAK2）/신호전도화전록격활자3（signal transducers and activators of transcription 3， STAT3）통로억제제WP1066대신경병이성동통적영향。방법12지체중180～200 g자성SD대서용수궤수자표법분위WP1066조급대조조（n＝6），균행쌍측좌골신경결찰수술，량조우술전1 d、술전급술후제3、5천분별경초내주사용량위10μl적WP1066（10 mmol/L용우이갑기아풍）혹이갑기아풍，우술전급술후제3、5、7、10、14천진행동물행위학검측，관찰대서대궤계、열급병동랭자격적반응。술후제14천처사대서，우L4～L6요팽대척수배각처취재，사용RT-PCR급Western blot검측STAT3、세포인자신호억제인자3（ suppressor of cytokine signaling 3， SOCS3）、 JAK2 mRNA급단백수평。결과대서궤계축족반사역치、열자격축족반사잠복기화랭통역치분별종제3、5、5천개시， WP1066조교대조조명현승고，차이구유통계학의의（P＜0.05）。여대조조상비， WP1066조STAT3、 SOCS3、 JAK2 mRNA표체균명현강저（ P＜0.05）； WP1066조린산화STAT3、 SOCS3、 JAK2단백수평균역명현강저（ P＜0.05）。결론 WP1066가명현개선대서신경병이성동통，가능위치료신경병이성동통제공신적파점。
Objective To evaluate whether the Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 ( STAT3) inhibitor WP1066 could be a novel therapeutic target for neuropathic pain and its molecu-lar mechnism.Methods Twelve female SD rats weighing 180-200 g were randomly divided into WP1066 group and control group ( n=6) using the random number table .Rats in both groups underwent bilateral chronic sciatic nerve constriction injury (bCCI).WP1066 (10μl, 10 mmol/L in dimethyl sulfoxide) or the equal volume of dime-thyl sulfoxide was applied through the intrathecal tube one day before surgery , just before surgery , and 3 and 5 days after surgery in the WP1066 group and control group , respectively .Behavior tests were performed before surgery and 3, 5, 7, 10, and 14 days after the surgery to observe the rats'reactions to mechanical , thermal, and cold stimula-tions.The rats were killed on the 14th postoperative day.The dorsal horn of the spinal cord (L4-L6) was harves-ted, followed by the reverse transcription polymerase chain reaction ( RT-PCR) and Western blotting to investigate the activation of the JAK2/STAT3 pathway.Results The pain-related behavior changes were significantly better in the WP1066 group than in the control group .WP1066 significantly inhibited the JAK2, suppressor of cytokine sig-naling 3 (SOCS3), and STAT3 mRNA in rats with bCCI, and significantly decreased the ratio of JAK2, SOCS3 and phosphorylation of STAT3 (p-STAT3) protein expression on the 14th postoperative day.Conclusions The administration of WP1066 can remarkably improve neuropathic pain in bCCI rats by inhibiting the STAT 3 signaling pathway.Therefore, WP1066 may be a novel target for neuropathic pain .
