褪黑素通过抑制大鼠脊髓损伤中炎性小体的激活来改善脊髓损伤。
Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats.
机构信息
Orthopedics Department, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Pudong, Shanghai, China.
Radiology Department, The 251st Hospital of Chinese PLA, Zhangjiakou, China.
出版信息
J Cell Biochem. 2019 Apr;120(4):5183-5192. doi: 10.1002/jcb.27794. Epub 2018 Sep 26.
BACKGROUND
The activation of inflammasomes plays an important role in the pathogenesis of spinal cord injury (SCI). In addition, the administration of melatonin (MT) has been shown to suppress the activation of inflammasomes. In this study, we aimed to investigate the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI.
METHODS
Basso-Beattie-Bresnahan (BBB) locomotion scaling was conducted to evaluate the therapeutic effect of MT on post-SCI locomotion recovery. In addition, the measurement of spinal cord water content was performed together with Nissl staining to evaluate the protective effect of MT against SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry (IHC) assay, Western blot analysis, and real-time polymerase chain reaction (PCR) were also conducted to clarify the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI.
RESULTS
BBB scores of SCI + MT rats were increased compared with the BBB scores of SCI rats, thus confirming the beneficial role of MT treatment in post-SCI functional recovery. Meanwhile, the administration of MT could alleviate SCI by reducing spinal cord water content and by exerting a neuroprotective effect on motor neurons. Furthermore, in the treatment of SCI, MT also attenuated cell apoptosis. Moreover, the relative expression of NLRP3, interleukin-1β (IL-1β), and caspase-1 were markedly elevated in the SCI group compared with that in the sham group, while the administration of MT reduced the expression of NLRP3 in SCI rats.
CONCLUSIONS
MT treatment accelerated the recovery of SCI by suppressing the activation of inflammasomes.
背景
炎症小体的激活在脊髓损伤(SCI)的发病机制中起着重要作用。此外,褪黑素(MT)的给药已被证明能抑制炎症小体的激活。在本研究中,我们旨在探讨 MT 治疗 SCI 的治疗作用的分子机制。
方法
巴索-比蒂-布雷森汉(BBB)运动评分用于评估 MT 对 SCI 后运动功能恢复的治疗效果。此外,还进行了脊髓含水量测量和尼氏染色,以评估 MT 对 SCI 的保护作用。末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)检测、免疫组织化学(IHC)检测、Western blot 分析和实时聚合酶链反应(PCR)也用于阐明 MT 治疗 SCI 的治疗作用的分子机制。
结果
SCI+MT 大鼠的 BBB 评分高于 SCI 大鼠,证实了 MT 治疗在 SCI 后功能恢复中的有益作用。同时,MT 的给药可以通过降低脊髓含水量和对运动神经元发挥神经保护作用来减轻 SCI。此外,在 SCI 的治疗中,MT 还能减轻细胞凋亡。此外,与假手术组相比,NLRP3、白细胞介素-1β(IL-1β)和半胱天冬酶-1在 SCI 组中的相对表达明显升高,而 MT 给药降低了 SCI 大鼠中 NLRP3 的表达。
结论
MT 治疗通过抑制炎症小体的激活加速了 SCI 的恢复。