蛇床子素减轻HIV gp120诱发的周围神经病理痛  

Osthole inhibits HIV gp120 induced neuropathic pain by down-regulating P2X_3 receptor in DRG

作　　者：易智华[1,2] 周聪发 雷琼琼[1] 胡夏菊[1] 李玲艳[1] 梁尚栋 YI Zhi-hua;ZHOU Cong-fa;LEI Qiong-qiong;HU Xia-ju;LI Ling-yan;LIANG Shang-dong(Nursing College,Nanchang University,Nanchang330006,China;Basic Medical College,Nanchang University,Nanchang330006,China)

机构地区：[1]南昌大学护理学院,江西南昌330006 [2]南昌大学基础医学院,江西南昌330006

出　　处：《中国药理学通报》2019年第5期680-685,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 31560276;81570735);江西省教育厅基金资助项目(No GJJ14319;GJJ150229;GJJ160105)

摘　　要：目的探讨蛇床子素(osthole,Ost)对背根神经节(dorsal root ganglia, DRG)P2X_3受体(P2X_3R)介导人类免疫缺陷病毒(human immunodeficiency virus,HIV)包膜糖蛋白gp120诱发周围神经病理痛的作用及机制。方法建立HIV gp120诱发周围神经病理痛大鼠模型,其中Ost给药组大鼠于建模术前7 d至术后14 d灌胃给药(40 mg·kg^(-1)·d^(-1))。检测各组大鼠机械痛缩足反射阈值(PWT)与热痛缩足反射潜伏期(PWL);实时定量PCR、蛋白印迹、免疫组化等方法检测DRG中神经元P2X_3R、炎性因子及ERK、p-ERK等的表达;全细胞膜片钳检测HEK293细胞三磷酸腺苷(ATP)激活电流及Ost对电流的影响。结果 gp120组大鼠PWT、PWL较假手术组(sham)减小,大鼠DRG中P2X_3R、TNF-αR及p-ERK表达均较sham组明显升高;gp120+Ost组大鼠PWT、PWL较gp120组增大,大鼠DRG中P2X_3R、TNF-αR及p-ERK表达均较gp120组降低;Ost抑制了转染人P2X_3R的HEK293细胞ATP激动电流。结论 Ost下调DRG神经元中P2X_3R,抑制相关信号通路与炎性反应,减轻gp120诱发的周围神经病理痛。Aim To investigate whether osthole can alleviate neuropathic pain induced by HIV gp120 and its mechanism. Methods The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in four groups of the rats,including sham group,sham combined with osthole treatment group,gp120 treatment group,and gp120 combined with osthole treatment group.The protein expression levels of the P2X 3 receptor,tumor necrosis factor-α receptor (TNF-αR),ERK,p-ERK in the L4-L6 dorsal root ganglia (DRG) were measured by Western blot.The mRNA expression level of P2X 3 receptor was assessed by real-time quantitative polymerase chain reaction (qPCR).The whole path clamp recording was used to measure HEK293 cell current activated by ATP. Results Osthole attenuated the mechanical and thermal hyperalgesia in gp120 treated rats and down-regulated P2X 3 receptor mRNA and protein expression in L4-L6 DRGs of gp120 treated rats.Additionally,osthole simultaneously decreased the expression of TNF-αR protein in L4-L6 DRGs and inhibited the phosphorylated ERK1/2 protein expression.Moreover,osthole reduced ATP activated current of HEK293 cells transfected with hP2X 3R. Conclusion Osthole decreases the mechanical and thermal hyperalgesia induced by gp120 through inhibiting P2X 3R in DRG.

关 键 词：蛇床子素 神经病理痛 P2X 3受体 背根神经节 人类免疫缺陷病毒包膜糖蛋白gp120 三磷酸腺苷 

分 类 号：R284.1[医药卫生—中药学] R322.85[医药卫生—中医学]