CD39在慢性偏头痛大鼠三叉神经脊束尾核中的 表达及作用

THE ROLE OF CD39 IN TRIGEMINAL NUCLEUS CAUDALIS OF RATS WITH CHRONIC MIGRAINE

摘要:

目的：观察CD39(外核苷三磷酸双磷酸酶1, ENTPD1) 在慢性偏头痛(chronic migraine, CM)大鼠三叉神经脊束尾核 (trigeminal nucleus caudalis, TNC) 中的表达变化，并探讨其在CM中的作用。 方法：采用腹腔隔日重复注射硝酸甘油 (nitroglycerin, NTG) 建立 CM 大鼠模型。使用 von Frey test 测定大鼠眶周和后足机械痛阈值。Western blot 检测 CM模型鼠中CD39 及中枢敏化关键指标降钙素基因相关肽 (calcitonin gene-related peptide,CGRP ) 的表达变化，免疫荧光检测 CD39 在 TNC 的表达及定位情况。通过侧脑室注射 CD39类似物 Apyrase增加外源性CD39表达来探究其对慢性偏头痛中枢敏化的影响。 结果：CM造模后，大鼠眶周和后足机械痛阈显著降低；Western blot结果显示TNC 中 CGRP 蛋白表达显著增加；CD39的表达明显减少。荧光染色显示 CD39 与神经元共定位；使用 CD39 类似物 Apyrase后 CGRP 表达明显降低。 结论：本研究表明CD39在慢性偏头痛中发挥保护作用，可能通过抑制中枢敏化改善慢性偏头痛的进程。

Abstract:

Objective: To investigate the role of CD39 (ectonucleoside triphosphate diphosphohydrolase 1,ENTPD1) within trigeminal mucleus caudalis (TNC) in the pathophysiological process of chronic migraine (CM) rats. Methods: Nitroglycerin (NTG) was repeatedly intraperitoneally injected (i.p.) in awake rats to establish CM model. Mechanical pain thresholds of periorbital region and hind paw were detected by von Frey test. Western blotting was performed to detect the expression of CD39 and CGRP protein in TNC. Localization of CD39 in TNC was detected by immuno?uorescence methods.The effect of CD39 analog Apyrase on CM was explored through intracerebroventricular injection (icv). Results: Repeated injection of NTG decreased pain thresholds in both periorbital region and mechanical withdrawal threshold (MWT) of the hind paw , and the protein expression of CGRP in TNC was significantly increased, while the expression of CD39 was markedly decreased. Immunofluorescence staining revealed that CD39 was expressed in neurons in TNC. Furthermore,the use of CD39 analog Apyrase significantly reduced the expression of CGRP. Conclusion: The decreased expression of CD39 in TNC may regulate the pathophysiological processes of CM by affecting central sensitization.