Departments of Pediatric Bone Oncology, Cangzhou Combine Traditional Chinese and Western Medicine Hospital, No. 31 Huanghe West Road, Cangzhou, 061000, Hebei, China.
Departments of Otorhinolaryngology and Geriatrics, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, 061000, Hebei, China.
J Bioenerg Biomembr. 2021 Jun;53(3):285-293. doi: 10.1007/s10863-021-09889-1. Epub 2021 Mar 16.
This study was conducted to investigate the protective effects of glycyrrhizin on a rat model of osteoarthritis and elucidate the underlying mechanism. Rat osteoarthritis was established by using medial meniscectomy (MMx) and an anterior cruciate ligament transaction (ACLT). Glycyrrhizin (2, 4, and 10 mg/kg) was administered by intra-articular knee injection for 12 weeks. Incapacitance test was performed to determine mechanical hyperalgesia. Enzyme-linked immunosorbent assay (ELISA) was performed to measure cartilage degradation and inflammation-related markers. Quantitative reverse transcription PCR (RT-qPCR) and Western blot were performed to determine the mRNA and protein levels of genes, respectively. The results demonstrated that treatment with glycyrrhizin ameliorated mechanical hyperalgesia and bilateral joints oedema in a rat model of osteoarthritis. Treatment with 10 mg/kg glycyrrhizin also suppressed serum enzymes including matrix metalloproteinase (MMP)-1, MMP-3, prostaglandin E2, and C-telopeptide of type II collagen (CTX-II). In addition to inhibition of cartilage matrix catabolic related markers, treatment with glycyrrhizin also decreased the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and iNOS in serum and cartilage. The underlying mechanism study demonstrated that treatment with glycyrrhizin inhibited HMGB1 and the TLR4/NF-κB signaling pathway. In summary, treatment with glycyrrhizin ameliorated cartilage degeneration and inflammation in osteoarthritis rats by the regulation of HMGB1 and the TLR4/NF-κB signaling pathway.
本研究旨在探讨甘草酸对骨关节炎大鼠模型的保护作用,并阐明其潜在机制。采用内侧半月板切除术(MMx)和前交叉韧带横断术(ACLT)建立大鼠骨关节炎模型。通过关节内膝关节注射给予甘草酸(2、4 和 10mg/kg)12 周。进行电容测试以确定机械性痛觉过敏。酶联免疫吸附测定(ELISA)用于测量软骨降解和炎症相关标志物。定量逆转录 PCR(RT-qPCR)和 Western blot 分别用于测定基因的 mRNA 和蛋白水平。结果表明,甘草酸治疗可改善骨关节炎大鼠的机械性痛觉过敏和双侧关节肿胀。10mg/kg 甘草酸治疗还抑制了包括基质金属蛋白酶(MMP)-1、MMP-3、前列腺素 E2 和 II 型胶原 C 端肽(CTX-II)在内的血清酶。除了抑制软骨基质分解代谢相关标志物外,甘草酸治疗还降低了血清和软骨中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α和诱导型一氧化氮合酶(iNOS)的水平。机制研究表明,甘草酸治疗通过抑制 HMGB1 和 TLR4/NF-κB 信号通路来改善骨关节炎大鼠的软骨退变和炎症。总之,甘草酸通过调节 HMGB1 和 TLR4/NF-κB 信号通路改善了骨关节炎大鼠的软骨退变和炎症。