Department of Orthopedics and Traumatology, Taipei Medical University Hospital, Taipei, Taiwan.
Osteoarthritis Cartilage. 2009 Nov;17(11):1485-93. doi: 10.1016/j.joca.2009.05.006. Epub 2009 May 19.
To study the effects of intra-articular injection of magnesium sulfate (MgSO(4)) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats.
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 OA+MgSO(4) group (n=7), the treated knee was injected with 500-microg (0.1-ml) MgSO(4) 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 MgSO(4) group (n=6), naïve rats received only MgSO(4) injections; in the control group (n=6), naïve 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 MgSO(4) on N-methyl-D-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes.
OA rats receiving intra-articular MgSO(4) injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO(4) treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA+MgSO(4) group as compared to the OA group. Moreover, MgSO(4) attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage.
Our results indicate that local intra-articular administration of MgSO(4) 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.
研究关节内注射硫酸镁（MgSO4）对骨关节炎（OA）发展的影响，并观察大鼠痛觉行为的变化。
采用关节内注射胶原酶（500 U）的方法诱导 Wistar 大鼠右膝 OA，左膝不做处理。在 OA+MgSO4 组（n=7）中，从胶原酶注射后 1 周开始，每周两次向患病膝关节内注射 500μg（0.1 ml）MgSO4，共 5 周；在 OA 组（n=7）中，相同膝关节内注射相同剂量的生理盐水。在 MgSO4 组（n=6）中，未处理的大鼠仅接受 MgSO4 注射；在对照组（n=6）中，未处理的大鼠仅接受生理盐水注射。在胶原酶注射前及注射后 1、2、4、6 和 8 周，测量大鼠 OA 发展过程中的痛觉行为（机械性痛觉过敏和热痛觉过敏），随后处死动物。在股骨髁、胫骨平台和滑膜中检查大体形态和组织病理学变化。采用免疫组织化学分析检测 MgSO4 对关节软骨细胞中 N-甲基-D-天冬氨酸（NMDA）受体亚单位 1 磷酸化（p-NR1）和细胞凋亡的影响。
接受关节内 MgSO4 注射的 OA 大鼠软骨退变程度明显低于接受生理盐水注射的大鼠。MgSO4 治疗还抑制了滑膜炎。与 OA 组相比，OA+MgSO4 组的机械性痛觉过敏和热痛觉过敏均显著改善。此外，MgSO4 减轻了 OA 病变软骨中 p-NR1 和软骨细胞凋亡。
我们的研究结果表明，在实验性大鼠 OA 模型中，（1）在胶原酶注射后局部关节内给予 MgSO4 通过抑制细胞 NMDA 受体磷酸化和凋亡来调节软骨细胞代谢；（2）减轻 OA 的发展；（3）同时减轻痛觉。
