DREAM基因沉默改善骨癌痛痛行为  

DREAM gene silencing attenuates pain-like behavior in rats with bone metastatic carcinoma

作　　者：于鹏[1] 程智刚[2] 王云姣[2] 肖旺频[1] 周红梅[1] 郭曲练[2] 

机构地区：[1]嘉兴学院附属第二医院麻醉科,浙江嘉兴314000 [2]中南大学湘雅医院麻醉科,湖南长沙410008

出　　处：《中国现代医学杂志》2014年第27期13-17,共5页China Journal of Modern Medicine

基　　金：浙江省自然科学基金(No:Y2091107)

摘　　要：目的探讨下游调控元件拮抗分子DREAM对骨转移癌痛疼痛行为学的影响。方法取健康雌性SD大鼠48只,体质量200-230 g,随机分为4组,即癌痛组（CP组,n=12,将5×10^5个Walker 256乳腺癌细胞注射到大鼠左胫骨上段骨髓腔）、假手术组（S组,n=12,注射同等体积的生理盐水）、空白载体组（BV组,n=12,Lenti.-GFP 10μL＋生理盐水10μL）、RNAi组（R组,n=12,Lenti.DREAMshR/GFP10μL＋生理盐水10μL）。所有大鼠均于接种前1 d（T0）,接种后7 d（T1）、14 d（T2）、19 d（T3）、21 d（T4）、25 d（T5）和28 d（T6）检测痛行为学变化（包括自发性缩足反射、患肢使用情况、机械痛阈和热痛阈）。术后20-25 d,行鞘内注射物质干预。术后28 d,取其L4脊髓,检测DREAM的表达变化。结果自发性缩足反射次数：与基础值（T0）及T1时比较,CP组、V组和R组在T2-T6时增加（P〈0.01）;与S组比较,CP组、V组和R组在T2-T6时增加（P〈0.01）;与CP组和V组比较,R组在T5、T6时减少（P〈0.01）。患肢使用情况评分：与基础值（T0）及T1时的值比较,CP组和V组在T2-T6时降低（P〈0.01或P〈0.05）,R组在T2-T5时降低（P〈0.01或P〈0.05）;与S组比较,CP组和V组在T2-T6时降低（P〈0.01或P〈0.05）,R组在T2-T5时降低（P〈0.01或P〈0.05）;与CP组及V组比较,R组在T6、T7时升高（P〈0.01）。机械痛阈：与基础值（T0）比较,各组在T1时均降低（P 0.01）,S组T2-T6时返回基线水平（P〉0.05）,但CP组、V组和R组T2-T6时降低（P〈0.01）;与T1时比较,S组T2-T6时升高（P〈0.01）,CP组和V组T2-T6时降低（P〈0.01）,R组在T2-T4时降低（P〈0.01）,在T5-T6时升高（P〈0.05或P〈0.01）;与S组比较,CP组、V组和R组在T1-T6时降低（P〈0.01）;与CP组和V组比较,R组在T5、T6时升高（P〈0.01）。热痛阈：各组不同时点值的差异无显著性,各时点组间差异无显著性。结论 DREAM基因沉默可改善骨癌痛痛行为。【Objective】To investigate the effects of DREAM gene silencing on pain-like behavior in rats with bone metastatic carcinoma. 【Methods】Forty-eight female healthy SD rats weighing 200-230 g were randomly divided into four groups, cancer pain group（CP, n =48, produced by inoculation of 5×10^5syngenetic Walker 256 rats mammary gland carcinoma cells to left tibia, and injected intrathecally with 20 μL of normal saline（NS）, once a day for 5 days）, sham group（S, n =12）, vehicle group（V, n =12, injected intrathecally with 10 μL vehicle plus 10μL NS,once a day for 5 days） and RNAi group（R, n =12, injected intrathecally with 10 μL of DREAM-shRNA plus 10μL NS, once a day for 5 days）. Focusing on the affected limb, counts of spontaneous flinching, affected limb use during ambulation, mechanical pain threshold and thermal pain threshold were measured one day before surgery（T0） and atday 7（T1）, day 14（T2）, day 19（T3）, day 21 d（T4）, day 25（T5） and day 28（T6） after surgery. The animals were sacrificed at day 28 after the procedure. The lumbar 4 segments in rats were removed for detection of DREAM.【Results】For the counts of spontaneous flinching, it went up（P〈0.01） from T2 to T6in groups CP, V and R as compared to that at T0 and T1in responding group, respectively. There was also an increase（P〈0.01） from T2 to T6in groups CP, V and R as compared with group S. Compared to groups CP and V, it was decreased at T5 and T6 in group R.As to the affected limb use score（0-4） during ambulation, it went down（P〈0.01 or P〈0.05） at T2-T6 in groups CP and V, and at T2-T5 in group R as compared with the baseline and that at T1, respectively. There was also an decrease（P〈0.01 or P〈0.05） at T2-T6 in groups CP and V,and at T2-T5 in group R as compared with group S. Compared to groups CP and V, it was increased（P〈0.01） at T5-T6 in group R. The mechanical threshold was significantly decreased（P〈0.01） at T1 as compared with the baseline in all

关 键 词：肿瘤 疼痛 钙结合蛋白 

分 类 号：R-332[医药卫生]