骨癌痛小鼠脊髓内皮素-1及其受体表达的变化  

Changes in expression of spinal endothelin-I and its receptors in a mouse model of bone cancer pain

作　　者：杨成伟 韩明明 康芳 黄祥 李娟 张志伟[2] Yang Chengwei;Hart Mingming;Kang Fang;Huang Xiartg;Li Juan;Chi Wai Cheung(Department of Anesthesiology, Arthui Provincial Hospital, Arthui Medical University, Hefei 230001, China;Department ofAnaesthesiology, Li Ka Shirtg Faculty of Medicirte, The University of Hong Kong, Hong Kortg 999077, Chin)

机构地区：[1]安徽医科大学附属省立医院麻醉科,合肥市230001 [2]香港大学李嘉诚医学院麻醉学系,999077

出　　处：《中华麻醉学杂志》2017年第12期1473-1476,共4页Chinese Journal of Anesthesiology

基　　金：安徽省国际科技合作计划（1503062021）

摘　　要：目的评价骨癌痛小鼠脊髓内皮素-1（ET-1）及其受体表达的变化。方法SPF级健康雄性C3H/HeN小鼠96只，4～6周龄，体重20～25 g，采用随机数字表法分为2组（n＝48）：假手术组（S组）和骨癌痛组（BCP组）。BCP组采用右侧股骨远端骨髓腔接种含有1×10^4个/μl NCTC 2472纤维肉瘤细胞的α-MEM 20 μl制备小鼠骨癌痛模型；S组给予α-MEM 20 μl。分别于接种前1 d（T0）、接种后4、7、10、14和21 d（T1-5）时测定机械痛阈（MWT）和自发抬足次数（NSF），于T0，2，4，5时随机取12只小鼠处死，取腰脊髓膨大，采用Western blot法检测脊髓ET-1、内皮素A受体（ETAR）和内皮素B受体（ETBR）的表达；采用实时定量PCR法检测其mRNA的表达水平。结果与T0时比较，S组T1时和BCP组T1-5时MWT降低，NSF增加（P〈0.05）；与S组比较，BCP组T2-5时MWT降低，NSF增加，T2，4，5时脊髓ET-1、ETAR和ETBR及其mRNA表达下调（P〈0.05）。结论小鼠骨癌痛的病理生理过程与脊髓ET-1及其受体表达下调有关。Objective To evaluate the changes in the expression of spinal endothelin-1（ET-1）and its receptors in a mouse model of bone cancer pain（BCP）.Methods Ninety-six healthy male SPF C3H/HeN mice, aged 4-6 weeks, weighing 20-25 g, were divided into 2 groups（n=48 each）using a random number table： sham operation group（group S）and BCP group.BCP was produced by injecting α-MEM 20 μl containing 1×10^4 cells/μl NCTC 2472 osteosarcoma cells into the distal medullary cavity of the right femur bone.In group S, α-MEM 20 μl was injected into the distal medullary cavity of the right femur bone.Mechanical paw withdrawal threshold（MWT）and the number of spontaneous flinches（NSF）were measured on 1 day before inoculation（T0）and 4, 7, 10, 14 and 21 days after inoculation（T1-5）. Twelve mice of each group were randomly sacrificed at T0, 2, 4, 5, and the lumbar enlargement segments of the spinal cord were harvested to detect the expression of ET-1, endothelin type A receptor and endothelin type B receptor protein and mRNA（using Western blot or real-time polymerase chain reaction）.Results The MWT was significantly lower and the NSF was higher at T1 in group S and at T1-5 in group BCP than at T0（P〈0.05）. Compared with group S, the MWT was significantly decreased and the NSF was increased at T2-5, and the expression of ET-1, endothelin type A receptor and endothelin type B receptor protein and mRNA was down-regulated at T2, 4, 5 in group BCP（P〈0.05）.Conclusion The pathophysiological process of BCP is associated with down-regulating the expression of spinal ET-1 and its receptors in mice.

关 键 词：受体 内皮素A 受体 内皮素B 受体 G蛋白偶联 骨肿瘤 疼痛 脊髓 

分 类 号：R730.2[医药卫生—肿瘤]