孕酮调节腺苷信号通路缓解大鼠神经病理性疼痛  

Progesterone alleviates neuropathic pain through regulation of adenosine signaling pathway in rats

作　　者：苏颖 胡志妍 贾改丽 李莉[3] 俞陈陈[4] 朱雅冰 谢红[2] SU Ying;HU Zhi-Yan;JIA Gai-Li;LI Li;YU Chen-Chen;ZHU Ya-Bing;XIE Hong(Department of Anesthesiology and Perioperative,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou 325027,China;Department of Anesthesiology,Second Affiliated Hospital of Soochow University,Suzhou 215000,China;Key Laboratory of Anesthesiology of Zhejiang Province,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou 325027,China;Department of Anesthesiology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院麻醉与围术期医学科,温州325027 [2]苏州大学附属第二医院麻醉科,苏州215000 [3]温州医科大学附属第二医院育英儿童医院浙江省麻醉学重点实验室,温州325027 [4]温州医科大学附属第一医院麻醉科,温州325015

出　　处：《中国疼痛医学杂志》2020年第4期256-264,共9页Chinese Journal of Pain Medicine

基　　金：浙江省自然科学基金青年项目(LQ18H040006);温州市公益性科技计划项目(Y20140548);浙江省公益技术研究计划/分析测试项目(LGC19H280007)。

摘　　要：目的:探索孕酮通过调节生殖内分泌靶器官睾丸和疼痛相关脑区终纹床核(bed nuclei of the stria terminals, BST)腺苷信号通路缓解坐骨神经结扎损伤(chronic constriction injury, CCI)模型大鼠神经病理性疼痛(neuropathic pain, NP)的机制。方法:雄性SD大鼠32只,随机分为4组(每组8只):假手术组、模型组、腺苷A1受体(A1R)拮抗剂组(DPCPX, 2 mg·kg-1)和孕酮组(PROG,12 mg·kg-1)。结扎后第14天开始各组连续14天分别给予溶剂、DPCPX或孕酮干预。进行L4-5背根神经节(dorsal root ganglion,DRG)和脊髓背角(spinal dorsal horn, SDH) 5’-核苷酸酶(ecto-5’-nucleotidase, CD73)免疫组化染色,并检测大鼠血清睾酮含量以及DRG、SDH、睾丸和BST的CD73或A1R蛋白表达变化。结果:与假手术组相比,模型组血清睾酮、DRG和SDH的CD73阳性细胞数以及DRG、SDH、睾丸和BST的A1R蛋白,显著下降或减少(P <0.05)。与模型组相比,PROG组和DPCPX组血清睾酮含量都有回升(P <0.05),但PROG组回升更显著(P <0.05);孕酮组DRG和SDH的CD73阳性细胞和A1R蛋白显著增多(P <0.05),但DPCPX抑制这些改变(P <0.05);孕酮组睾丸和BST的CD73蛋白和A1R蛋白均显著升高(P<0.05)。与孕酮组相比,DPCPX对睾丸和BST的CD73蛋白表达的抑制作用无统计学意义,但显著抑制了A1R蛋白水平恢复(P <0.05)。结论:孕酮通过调节DRG、SDH与生殖内分泌靶器官睾丸和疼痛相关脑区BST腺苷信号通路的上游信号CD73和下游信号A1R,缓解了大鼠NP。Objective: To investigate the effects of progesterone on neuropathic pain(NP) and its possible mechanisms regarding the adenosine signal pathway of the reproductive endocrine target organ testis and the bed nuclei of the stria terminals(BST), a brain area relative with pain, in rats with chronic constriction injury(CCI). Methods: Thirty-two adult, male SD rats were randomly divided into 4 groups(8 in each): sham-operated, CCI model, adenosine A1 receptor(A1 R) antagonist(DPCPX, 2 mg·kg-1), and progesterone group(PROG, 12 mg·kg-1). Rats in the four groups were administrated with solvent, DPCPX, or progesterone respectively for 14 days continuously starting from day 14 after surgery. Immumohistochemical staining was used to detect the 5’-nucleotidase(CD73) in L4-5 dorsal root ganglion(DRG) and spinal dorsal horn(SDH). The serum testosterone content was detected, and the protein variations of CD73 or A1 R were detected in DRG, SDH, testis, and BST. Results: Compared with CCI model group, the progesterone group showed significantly increased serum testosterone level(P < 0.05), which could be reversed by DPCPX(P < 0.05) The numbers of CD73 positive cells in DRG and SDH of progesterone group were significantly increased than that of CCI model group(P < 0.05), but DPCPX reversed these changes(P < 0.05). The expressions of A1 R protein in DRG and SDH of progesterone group exhibited similar changes as the numbers of CD73 positive cells. Compared to CCI model group, the progesterone group presented significantly increased CD73 protein and A1 R protein in testis and BST(P < 0.05). Meanwhile, the inhibitions of CD73 protein in testis and BST induced by DPCPX were not statistically significant compared to progesterone group. However, the alterations of A1 R protein in testis and BST induced through DPCPX were apparent(P < 0.05). Conclusion: Progesterone alleviates NP in rats by regulating CD73 and A1 R, that’re the upstream and the downstream signal of the adenosine signal pathway, in DRG, SDH, reproductive endocrine ta

关 键 词：神经病理性疼痛 坐骨神经结扎损伤 5’-核苷酸酶 腺苷A1受体 生殖内分泌 终纹床核 

分 类 号：R741.041[医药卫生—神经病学与精神病学]