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褪黑素通过抑制膝关节软骨表面的炎症和相关氧化应激来减轻大鼠骨关节炎的进展。

Melatonin Attenuates the Progression of Osteoarthritis in Rats by Inhibiting Inflammation and Related Oxidative Stress on the Surface of Knee Cartilage.

机构信息

Department of Orthopaedics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Anesthesiology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Orthop Surg. 2022 Sep;14(9):2230-2237. doi: 10.1111/os.13408. Epub 2022 Jul 27.

Abstract

OBJECTIVE

To investigate the correlation between melatonin and osteoarthritis (OA) in rats. To explore the relevant mechanisms in the occurrence and development of osteoarthritis in rats, and to further understand the disease of osteoarthritis.

METHODS

Forty healthy 6-month-old male SD rats were randomly divided into two groups: sham and drug intervention groups. Pre-OA modeling, enzyme-linked immunosorbent assay was employed to detect the levels of IL-1β, IL-6, COX-2, and melatonin in the serum of the rats in each group. For OA modeling, we administered an injection of papain into the knee cavity of all rats. The levels of IL-1β, IL-6, and COX-2 in the serum of rats in each group were detected 2 weeks after the modeling. Additionally, 2 weeks after the modeling, the rats in the drug intervention group were intraperitoneally injected with melatonin antagonists. The rats in the sham group were intraperitoneally injected with normal saline for 2 weeks. The levels of IL-1β, IL-6, and COX-2 in the serum of each group were measured at the second, third, and fourth weeks after the drug intervention, and the levels of melatonin in the serum were measured at the second week after the drug intervention. Finally, the rats were euthanized by cervical dislocation, and pathological sections were collected from the knee joint to observe the pathological tissue changes under a microscope, and Mankin score was determined. The independent samples t-test method was used for analysis.

RESULTS

The imaging examination after the drug intervention showed that the modeling of knee osteoarthritis in rats was successful. In the pathological findings, HE staining showed a legible cartilage structure of each layer, with cartilage proliferation and partial cartilage tearing to the radial layer. The tide line was intact; toluidine blue staining revealed more obvious changes. The differences among the mean values of IL-6, IL-1β, and COX-2 measured in each period were statistically significant (t = 5.50, p < 0.05). The measured mean values of IL-6, IL-1β, and COX-2 revealed statistically significant differences among the groups (t = 2.01, p < 0.05). The intergroup comparison of the Mankin scores in each period showed statistically significant differences.

CONCLUSION

Melatonin may inhibit inflammation and associated oxidative stress on the surface of knee cartilage. It may be related to the repair and regeneration of articular surface cartilage during the development of OA in the rat knee joint.

摘要

目的

探讨褪黑素与大鼠骨关节炎(OA)的相关性。旨在探讨褪黑素在大鼠 OA 发生发展中的相关机制,进一步了解 OA 疾病。

方法

40 只 6 月龄健康雄性 SD 大鼠随机分为两组:假手术组和药物干预组。在 OA 造模前,采用酶联免疫吸附试验检测各组大鼠血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、环氧化酶-2(COX-2)和褪黑素的水平。OA 造模后,所有大鼠均向膝关节腔内注射木瓜蛋白酶。造模后 2 周,检测各组大鼠血清中 IL-1β、IL-6 和 COX-2 的水平。此外,造模后 2 周,药物干预组大鼠腹腔注射褪黑素拮抗剂,假手术组大鼠腹腔注射生理盐水 2 周。药物干预后第 2、3、4 周,测量各组大鼠血清中 IL-1β、IL-6 和 COX-2 的水平,药物干预后第 2 周测量血清中褪黑素的水平。最后,大鼠颈椎脱臼处死,收集膝关节病理切片,在显微镜下观察病理组织变化,测定 Mankin 评分。采用独立样本 t 检验方法进行分析。

结果

药物干预后的影像学检查显示,大鼠膝骨关节炎建模成功。在病理发现中,HE 染色显示各层清晰的软骨结构,软骨增生,部分软骨向放射层撕裂,潮线完整;甲苯胺蓝染色显示出更明显的变化。各时期测量的 IL-6、IL-1β和 COX-2 的平均值之间的差异具有统计学意义(t=5.50,p<0.05)。各组间 IL-6、IL-1β和 COX-2 测量的平均值之间差异具有统计学意义(t=2.01,p<0.05)。各时期组间 Mankin 评分的比较差异具有统计学意义。

结论

褪黑素可能抑制膝软骨表面的炎症和相关氧化应激,这可能与大鼠膝关节 OA 发展过程中关节表面软骨的修复和再生有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b97/9483081/cedb9279336d/OS-14-2230-g003.jpg

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