腺相关病毒介导的脑源性神经营养素对脊神经结扎大鼠的镇痛机制  

Analgesic mechanism of brain⁃derived neurotrophin factor mediated by adeno⁃associated virus in spinal nerve ligation rats

作　　者：黄爱苹[1] 章巧琪 谷桢[1] 薛纯纯[1] 王开强[1] 谢磊[1] HUANG Aiping;ZHANG Qiaoqi;GU Zhen;XUE Chunchun;WANG Kaiqiang;XIE Lei(Department of Pain Management,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai Univer-sity of Traditional Chinese Medicine,Shanghai 200071,China)

机构地区：[1]上海中医药大学附属市中医医院疼痛科,上海200071 [2]上海中医药大学附属曙光医院宝山分院肾内科,上海201999

出　　处：《实用医学杂志》2020年第22期3054-3058,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金青年基金项目(编号:81603485);上海市进一步加快中医药事业发展三年行动计划项目中医优势病种培育建设项目(编号:ZY(2018⁃2020)⁃ZYBZ⁃06);上海市进一步加快中医药事业发展三年行动计划项目中医重点专科培育项目(编号:2018⁃2020)。

摘　　要：目的探讨脊神经结扎(spinal nerve ligation,SNL)大鼠鞘内注射腺相关病毒(adeno⁃associated virus,AAV)介导的脑源性神经营养素(BDNF)对神经病理痛的影响及可能的机制。方法将SD大鼠随机分为:正常组、SNL组、生理盐水(NS)组、空载(AAV0)组、BDNF组、BDNF+KCC2拮抗剂(Furos)组、BDNF+NS组。于造模前、注射后0、3、7、14、21 d分别测量大鼠患侧痛阈值。结束后WB检测脊髓背角BDNF、KCC2蛋白表达。结果造模后,各组与正常组比较痛阈值明显下降(P<0.001);注射后14、21 d,BDNF组与SNL、NS、AAV0组比较痛阈值升高(P<0.001)。BDNF+Furos组注射后痛阈值明显低于BDNF、BDNF+NS组(P<0.001)。注射后21 d,BDNF组与SNL、NS、AAV0组比较BDNF、KCC2表达上调(P<0.001);BDNF+Furos组与BDNF、BDNF+NS组比较,KCC2表达下降(P<0.001)。结论AAV介导的BDNF在鞘内表达对SNL大鼠可起到镇痛作用,此作用与KCC2的上调有关。Objective To explore the effect of intrathecal injection of adeno⁃associated virus(AAV)⁃mediated brain⁃derived neurotrophin factor(BDNF)in spinal nerve ligation(SNL)rats on neuropathic pain and its possible mechanism.Methods Fifty⁃six SD rats were randomly divided into normal,SNL,normal saline(NS),BDNF⁃free AAV(AAV0),AAV⁃BDNF(BDNF),AAV⁃BDNF+potassium chloride cotransporter 2(KCC2)antagonist(BDNF+Furos)and AAV⁃BDNF+NS(BDNF+NS)groups.Mechanical withdrawal thresholds(MWTs)and thermal withdrawal latencys(TWLs)of the rats in each group were measured before modeling and 0,3,7,14,and 21 days after intrathecal injection.The expression of BDNF and KCC2 in the spinal dorsal horn was detected by Western Blot after test.Results Compared with the normal group,the MWTs and TWLs of other groups decreased significantly after modeling(P<0.001).As compared with the SNL,NS and AAV0 groups,the MWT and TWL of the BDNF group increased at 14 and 21 days after injection(P<0.001).After intrathecal injection,the MWT and TWL of the BDNF+Furos group was significantly lower than those of the BDNF and BDNF+NS groups(P<0.001).At 21 days after injection,the expression of BDNF and KCC2 in the BDNF group was signifi⁃cantly higher than those in SNL,NS and AAV0 groups(P<0.001).The expression of KCC2 in the BDNF+Furos group decreased compared to those in the BDNF and BDNF+NS groups(P<0.001).Conclusion The intrathecal expression of BDNF mediated by AAV can play an analgesic role in SNL rats,which is related to the upregulation of KCC2.

关 键 词：脑源性神经营养素 腺相关病毒 钾离子⁃氯离子共转运体2 脊神经结扎模型 神经病理痛 

分 类 号：R741.05[医药卫生—神经病学与精神病学]