齐墩果酸抑制骨关节炎大鼠肌肉氧化损伤及软骨下骨异常骨重建

doi:10.11843/j.issn.0366-6964.2022.11.033

Abstract

Abstract: We aimed to investigate the effects of oleanolic acid (OLA) on oxidative damage of muscle and abnormal subchondral bone reconstruction in rats with osteoarthritis (OA). Eighteen Sprague-Dawley rats were selected and randomly divided into three groups:the control group (CON group), the model group (OA group) and the oleanolic acid administration group (OLA group).The OA and OLA groups were established using anterior cruciate ligament dissection combined with partial meniscectomy (ACLT+PMMx) to establish a rat knee OA model, and the CON group underwent sham surgery. Rats in the OLA group were given 50 mg·(kg·d)^-1 OLA by gavage daily, and rats in the CON and OA groups were given equal volumes of sterile saline containing 20 mL·L^-1 Tween 80. After four consecutive weeks of dosing, knee, quadriceps and serum samples were taken. The rats were tested for joint pain using knee extension vocalization test and heat sensitivity test. Enzyme-linked immunosorbent assay to detect the levels of citrate synthase (CS), myosin heavy chain (MHC), interleukin 1 (IL-1) and interleukin 6 (IL-6) in rat muscle and the levels of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-Ⅰ) in rat serum. Western blot was used to detect changes in Nrf2/NQO1/HO-1 pathway protein expression in muscle tissue. Micro-CT was used for subchondral bone scanning and quantitative analysis of bone tissue microstructure. The results showed that compared with the OA group, OLA could reduce the OA pain score (P<0.05), activate the muscle Nrf2/NQO1/HO-1 pathway, promote the expression of muscle CS and MHC, and down-regulate the levels of IL-1 and IL-6 (P<0.05). In addition, percent bone volume (BV/TV), bone mineral density (BMD) and trabecular thickness (Tb.Th) were significantly increased (P<0.05) and expression of bone metabolic markers OCN and CTX-Ⅰ were significantly decreased (P<0.05) in subchondral bone of rats after OLA supplementation. The results suggest that OLA can inhibit the joint pain response in OA rats, inhibit muscle dysfunction in OA rats by regulating the Nrf2/NQO1/HO-1 pathway, improve the biomechanical properties and microstructural changes of subchondral bone in early OA, thereby delaying the occurrence of abnormal bone remodeling of subchondral bone in OA rats.

Key words: osteoarthritis, oleanolic acid, subchondral bone, muscle, oxidative stress

CLC Number:

S857.165

MA Tianwen, LÜ Liangyu, YU Yue, JIA Lina, CHEN Hong, TANG Jilang, ZHAO Mingchao, WANG Xinyu, ZHANG Jiantao, GAO Li. Oleanolic Acid Inhibits Muscle Oxidative Damage and Abnormal Subchondral Bone Remodeling in Osteoarthritis Rats[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(11): 4081-4088.

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Oleanolic Acid Inhibits Muscle Oxidative Damage and Abnormal Subchondral Bone Remodeling in Osteoarthritis Rats

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