SAHA对骨癌痛大鼠脊髓背角内谷氨酸转运体1表达的影响

目的:通过观察辛二酰苯胺异羟肟酸(Suberoylanilide Hydroxamic Acid,SAHA)对于骨癌痛(cancerinduced bone pain,CIBP)大鼠脊髓内谷氨酸转运体1(glutamate transporter 1,GLT-1)表达的影响,探讨GLT-1参与SAHA镇痛的相关机制。方法:将体重180~220 g雌性SD大鼠随机分为4组:Sham+vehicle组(A)、Sham+SAHA组(B)、CIBP+vehicle组(C)、CIBP+SAHA组(D)。经腹膜腔注射50 mg/kg SAHA,1/d。利用von Frey纤维测量大鼠手术侧机械缩足反射阈值(paw withdrawal threshod,PWT)。上述4组大鼠在不同时间点处死后取其腰膨大段脊髓,应用免疫组织化学染色和Western Blot方法观察大鼠腰膨大节段手术侧脊髓背角内GLT-1的表达情况。结果:与A组相比,C组大鼠PWT自术后第7 d开始显著下降,且一直持续至术后第14 d(P0.01),脊髓背角内GLT-1水平逐渐下调,呈时间依赖性(P0.05)。D组与C组相比,PWT升高(P0.05),术侧脊髓背角内GLT-1表达增加(P0.05)。结论:腹膜腔注射SAHA能够有效缓解骨癌痛,其部分机制可能与促进脊髓背角内GLT-1的表达有关。

The effect of suberoylanilide hydroxamic acid on the expression of glutamate transporter 1 in cancer-induced bone pain rats

Objective:To observe the expression level of glutamate transporter 1 (GLT-1) in spinal dorsal horn (SDH) of the cancer-induced bone pain (CIBP) rats,and then elucidate the role of suberoylanilide hydroxamic acid (SAHA) in analgesia.Methods:Healthy female Sprague-Dawley rats weighting 180 ～220 g were randomly divided into four groups:Sham + vehicle group (A),Sham + SAHA group (B),CIBP + vehicle group (C),CIBP + SAHA group (D).In B and D groups,SAHA was injected intraperitoneally (i.p.) once a day from post-operation day (POD) 1 to 14 at the dosage ofS0 mg/kg.Paw withdrawal threshold (PWT) was tested by Von Frey filament.All the rats in abovementioned 4 groups were executed at different time points to collect the lumbar spinal cord,and the expression of GLT-1 was detected using immunofluorescent histochemistry and Western Blot methods.Results:Compared with group A,the PWT was significantly decreased on POD 7 till POD 14 in group C (P ＜ 0.01),and the expression level of GLT-1 declined gradually in a time-dependent manner (P ＜ 0.05).Compared with group C,the PWT was elevated (P ＜ 0.01) and the expression of GLT-1 improved in group D (P ＜ 0.01) after SAHA treatment.Conclusions:Cancer-induced bone pain can be alleviated by i.p.administration of SAHA,and the promotion of GLT-1 expression might be associated with the analgesic effect of SAHA.