脊髓CCR-8表观遗传学调控在小鼠切口痛模型痛觉敏化的作用  

The mechanism of spinal CCR-8 participating hyperalgesia in a mouse model of incisional pain

作　　者：刘芳芳[1] 田蜜[1] 纪木火[1] 吴智方[1] 金利[2] 李伟彦[1] 

机构地区：[1]南京大学医学院临床学院,南京军区南京总医院麻醉科,210002 [2]南京大学医学院临床学院南,京军区南京总医院麻醉科,210002

出　　处：《临床麻醉学杂志》2014年第5期482-484,共3页Journal of Clinical Anesthesiology

摘　　要：目的探讨脊髓CCR-8表观遗传学调控在小鼠切口痛模型痛觉敏化中的作用。方法64只成年雄性小鼠随机均分为四组：对照组（C组）、切口痛组（INC组）、切口痛＋组蛋白去乙酰化酶抑制剂组（INC＋SAHA组）和切口痛＋组蛋白乙酰转移酶抑制剂组（INC＋ACA组），其中ICN组、INC＋SAHA组和INC＋ACA组小鼠建立切口痛模型。INC＋SAHA组和INC＋ACA组小鼠分别于术前1d、术前2h及术后1～4d每天上午行为学测试后腹腔分别注射50mg／kg的SAHA和5mg／kg的ACA。每组各取10只分别于术前1d（T0）、2h（T1）及术后1d（T2）、2d（L）、3d（T4）、4d（T5）、5d（T6）、6d（T7）、7d（T8）、14d（T9）检测疼痛行为学，每组另外6只于术后第4天检测脊髓H3K9和CCR-8蛋白表达。结果与C组比较，T2～T7时INC组小鼠机械缩足阈值（MWT）明显降低、热缩足潜伏期（PWL）明显缩短（P〈0．05）；与ICN组比较，T5～T8时INC＋SA—HA组MWT明显降低、PWL明显缩短（P〈0．05），T2～T7时INC＋ACA组MWT明显升高和PWL明显延长（P〈0．05）。术后第4天，与C组比较，INC组H3K0和CCR-8蛋白表达明显增加（P〈0．05）；与ICN组比较，INC＋SAHA组H3K9和CCR-8蛋白表达明显增加（P〈0．05），INC＋ACA组H3K9和CCR-8蛋白表达明显减少（P〈0．05）。结论脊髓CCR-8通过表观遗传学机制调控参与小鼠切口痛模型痛觉敏化形成。Objective To explore the effects of epigenetic regulation of spinal CCR-8 on hyperalgesia in a mouse model of incisional pain. Methods Sixty-four adult male mice were randomly divided into 4 groups： control group （group C）, incisional pain model group （group INC）, incisional pain model＋SAHA group （group INC＋SAHA） and incisional pain model＋ACA group （group INC＋ ACA）. Incisional pain model was established in the groups INC, INC＋SAHA and INC＋ACA. Mice in the groups INC＋SAHA and INC＋ ACA received intraperitoneal injection of SAHA （50 mg/kg） and ACA （5 mg/kg） 1 d before incision, 2 h before incision, and each morning after nociceptive tes- ting for 4 days. The paw Withdrawal Mechanical Threshold （MWT） and Paw Withdrawal Thermal Latency （PWL） of 10 mice out of each group were tested on 1 d （T0） and 2 h （T1） preoperation and 1 h （＇I＂2）, 2 d （T3）, 3 d （T4）, 4 d （T5）, 5 d（T6）, 6 d （T7）, 7 d（T8） and 14 d （T9） postoperation. The expression of spinal H3 K9 and CCR-8 of the 6 mice left in each group was tested on 4 d postoperation. Results Compared with the group C, MWT and PWL were lower at T2-T7 postoperation in the group INC （P〈0. 05）. Compared with the group INC, MWT and PWL were lower at T5-T8 postoperation in the group INC＋SAHA （P〈0. 05）, but MWT and PWL were higher at T2-T7 in the group INC＋ACA. The expression of H3K9 and CCR-8 at T5 was increased compared with the group C. Compared with the group INC, the expression of H3 K9 and CCR-8 was increased in the group INC＋ SAHA （P〈0.05）, and was decreased in the group INC＋ACA （P〈0. 05）. Conclusion Spinal CCR- 8 regulates the development of hyperalgesia in a mouse model of incisional pain through epigenetic mechanism.

关 键 词：切口痛 表观遗传学 痛觉敏化 

分 类 号：R614[医药卫生—麻醉学]