Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes
Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes
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DOI：
10.1016/j.joca.2009.05.006
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发表时间：
2009-11-01
影响因子：
7
通讯作者：
Jean, Y. H.
中科院分区：
文献类型：
--
作者：
Lee, C. H.;Wen, Z. H.;Jean, Y. H.
目的：研究硫酸镁关节腔内注射对大鼠骨性关节炎(OA)形成的影响及其对大鼠伤害性行为的影响。方法：采用大鼠右膝关节关节内注射胶原酶(500U)复制大鼠骨关节炎模型，左侧膝关节不给予治疗。CA+硫酸镁组(n=7)从注射胶原酶后1周开始，每周2次注射硫酸镁500 mg(0.1-ml)，连续注射5周；骨关节炎组(n=7)注射等量生理盐水。在硫酸镁组(n=6)，幼鼠只注射硫酸镁；对照组(n=6)，幼鼠只注射生理盐水。分别于注射胶原酶前及注射胶原酶后1、2、4、6、8周，测定其痛觉行为(机械性超敏和热痛敏)，然后处死动物。大体观察股骨髁、胫骨平台和滑膜的大体形态和组织病理学。免疫组织化学方法检测硫酸镁对关节软骨细胞N-甲基-D-天冬氨酸受体1亚单位1磷酸化(p-NR1)和细胞凋亡的影响。结果：硫酸镁关节腔内注射组大鼠关节软骨退变程度明显低于生理盐水组。硫酸镁治疗对滑膜炎症也有抑制作用。与OA组相比，OA+MgSO4组的机械性痛觉过敏和热痛敏症状有明显改善。结论：胶原酶注射后局部关节内注射硫酸镁可通过抑制细胞NMDA受体的磷酸化和细胞凋亡来调节软骨细胞的代谢，延缓骨性关节炎的发展，同时减少伤害性感觉。皇冠版权所有(C)2009，由爱思唯尔有限公司代表国际骨性关节炎研究会出版。版权所有。
Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO4) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats.Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the CA + MgSO4 group (n = 7), the treated knee was injected with 500-mu g (0.1-ml) MgSO4 twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO4 group (n = 6), naive rats received only MgSO4 injections; in the control group (n = 6), naive rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO4 on N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes.Results: OA rats receiving intra-articular MgSO4 injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO4 treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO4 group as compared to the OA group. Moreover, MgSO4 attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage.Conclusions: Our results indicate that local intra-articular administration Of MgSO4 following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown Copyright (C) 2009 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. All rights reserved.