PGC-1α介导线粒体生物发生对骨癌痛伴发镜像痛的影响  

The effect of PGC-1αmediates mitochondrial biogenesis on bone cancer pain and concurrent mirror-image pain

作　　者：刘佳霖 张钰 段柯杨 王敬萱 王雪莹 孙涛 LIU Jia-lin;ZHANG Yu;DUAN Ke-yang;WANG Jing-xuan;WANG Xue-ying;SUN Tao(Department of Pain Medicine,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China)

机构地区：[1]山东第一医科大学附属省立医院疼痛科,济南250021

出　　处：《中国疼痛医学杂志》2024年第9期653-663,共11页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(81972145)。

摘　　要：目的:探讨过氧化物酶体增殖物激活受体-γ共激活因子-1α (peroxisome proliferator-activated receptor-γ coactivator-1α, PGC-1α)调控线粒体生物发生对骨癌痛伴发镜像痛的影响。方法:第一部分实验:成年雌性SD大鼠按照随机数字表法分成2组,假手术组(Sham组)与骨癌痛组(bone cancer pain, BCP组),每组10只。第二部分实验:大鼠按照随机数字表法分成3组,Sham+vehicle组、BCP+vehicle组、BCP+ZLN(ZLN005,PGC-1α激活剂组),每组25只。将MRMT-1大鼠乳腺癌细胞注入左胫骨髓腔建立BCP大鼠模型,Sham组大鼠注射等体积Hank's平衡盐溶液。第二部分实验中,BCP+ZLN组大鼠鞘内注射ZLN005(单次单剂量100μg/30μl),Sham+vehicle组与BCP+vehicle组注射等体积溶剂。Western blot用于分析大鼠脊髓中PGC-1α、Nrf1和Tfam蛋白表达量。q PCR用于分析mt DNA相对拷贝数。免疫荧光双标染色分析PGC-1α的分布与细胞定位。结果:单侧癌细胞接种诱导BCP大鼠双侧后爪出现机械性痛觉过敏。ZLN005鞘内注射可减轻BCP大鼠双侧后爪的机械性痛觉过敏。在BCP大鼠的脊髓中观察到PGC-1α、Nrf1、Tfam和mt DNA相对拷贝数水平下降。鞘内注射ZLN005后,PGC-1α、Nrf1、Tfam和mt DNA相对拷贝数的水平升高。PGC-1α在同侧和对侧脊髓背角均有分布。PGC-1α的荧光强度在BCP大鼠双侧脊髓中出现下降。PGC-1α主要与神经元共定位。结论:脊髓中的线粒体生物发生的损伤促进了骨癌痛伴发镜像痛的发生发展。PGC-1α激活介导线粒体生物发生缓解骨癌痛及其伴发的镜像痛。Objective:To investigate the effects and mechanisms of peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)regulated mitochondrial biogenesis on bone cancer pain and concurrent mirror-image pain.Methods:In the first part of the experiment,adult female SD rats were randomly divided into 2 groups using a table of random numbers,Sham group and BCP(bone cancer pain)group,with 10 rats in each group.In the second part of the experiment,the rats were randomly divided into 3 groups using a table of random numbers,Sham+vehicle group,BCP+vehicle group,BCP+ZLN(ZLN005,PGC-1αactivator)group,with 25 rats in each group.MRMT-1 breast cancer cells were injected into the medullary cavity of the left tibia to establish BCP rat model,and Sham group rats were injected with equal volume of Hank's balanced salt solution.In the second part of the experiment,rats in the ZLN group were injected intrathecally with ZLN005(100μg/30μl),and the Sham group and vehicle group rats were injected with an equal volume of vehicle.The levels of PGC-1α,Nrf1, and Tfam in the spinal cord of the rats were analysed by western blot. The mtDNA copy numberexpression was analysed by qPCR. The localization of PGC-1α was analysed by immunofluorescence. Results:Mechanical hyperalgesia was induced in the bilateral hind paws of rats by intra-bone marrow injection of cancercells. Intrathecal injection of ZLN005 attenuated mechanical hyperalgesia of BCP rats. In the spinal cord ofBCP rats, a decreased in levels of PGC-1α, Nrf1, Tfam and relative mtDNA copy number were observed. Theexpression of PGC-1α, Nrf1, Tfam and relative mtDNA copy number was elevated after administration withZLN005. The distribution of PGC-1α in the spinal dorsal horn was demonstrated on both sides. The fluorescenceintensity of PGC-1α was declined in BCP rats. PGC-1α was mainly located in neurons. Conclusion: In the spinalcord, damage to mitochondrial biogenesis facilitated the development of bone cancer pain concomitantwith mirror-image pain. PGC-1α activation can a

关 键 词：骨癌痛 镜像痛 线粒体质量控制 线粒体生物发生 PGC-1Α 

分 类 号：R738.1[医药卫生—肿瘤]