葛根素干预软骨氧化应激和Nrf2/HO-1通路改善PTOA大鼠软骨退变的机制

doi:10.11843/j.issn.0366-6964.2023.09.033

Abstract

Abstract: The aim of this experiment was to investigate the mechanism of puerarin in the intervention of oxidative stress of cartilage and the improvement of Nrf2/HO-1 pathway on cartilage degeneration in rats with post-traumatic osteoarthritis (PTOA), and to explore the therapeutic effect of puerarin on osteoarthritis. Forty male Sprague-Dawley rats were randomly divided into four groups:control group (n=8), model group (n=8), celecoxib group (n=8) and puerarin group (n=16). Puerarin group was divided into low dose group (n=8) and high dose group (n=8). The PTOA model was established by anterior cruciate ligament transection (ACLT) in all groups except the control group. Low-dose group (50 mg·kg^-1), high-dose group (100 mg·kg^-1) and celecoxib group (2.86 mg·kg^-1) were administered by gavage, and the control group was given equal amount of saline for 5 weeks. The degree of joint swelling, cold sensitivity response and knee extension vocalization tests were performed weekly to assess the degree of joint swelling and pain in rats. After the administration, knee joint and serum samples of rats in each group were collected. The tibial and femoral tissues were subjected to HE staining and a modified Mankin score to assess histopathological changes. The histopathological changes were evaluated using the Mankin method. The levels of MMP3, MMP13 and ADAMTS4 in rat cartilage, as well as the levels of CTX-Ⅱ and COMP in serum were measured to evaluate the improvement of puerarin on cartilage degeneration in rats with osteoarthritis. To evaluate the protective effect of puerarin on oxidative damage in rats, the activity of antioxidant enzymes (SOD, GSH-Px, and CAT) in rat serum, the content of MDA and the level of Nrf2/HO-1 pathway in rat cartilage were measured. Detection of IL-1β, IL-6 and TNF-α in rat serum to evaluate the anti-inflammatory effect of puerarin on the body. The results showed that, compared with the model group, the high dose group intervention could significantly reduce the degree of joint swelling and pain response in rats, improve the degree of articular cartilage injury, reduce the Mankin score (P<0.01), activate the Nrf2/HO-1 pathway in cartilage tissue, inhibit the expression of MDA, MMP3, MMP13, and ADAMTS4 (P<0.05), upregulate the activity of antioxidant enzymes in serum (P<0.01), and inhibit the inflammatory factor IL-1β, IL-6 and TNF-α and the levels of cartilage metabolic markers CTX-Ⅱ and COMP in serum (P<0.05). In summary, puerarin improves cartilage degeneration in PTOA rats by activating the Nrf2/HO-1 pathway to inhibit oxidative stress and inflammatory damage.

Key words: puerarin, post-traumatic osteoarthritis, cartilage degeneration, oxidative stress, Nrf2/HO-1 pathway

CLC Number:

S857.16

CHEN Hong, RUAN Hongri, MA Tianwen, LI Yanan, MIAO Xue, YANG Wenyue, GAO Li, WEI Chengwei. The Mechanism of Puerarin Improving Cartilage Degeneration in PTOA Rats by Interfering with Oxidative Stress and Nrf2/HO-1 Pathway of Cartilage[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(9): 3951-3963.

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The Mechanism of Puerarin Improving Cartilage Degeneration in PTOA Rats by Interfering with Oxidative Stress and Nrf2/HO-1 Pathway of Cartilage

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