| Objective To explore the effect of Tanshinone IIA on cartilage injury in knee osteoarthritis (KOA) rabbits by regulating the silent information regulator 1/nuclear factor-erythroid 2 related factor 2/heme oxygenase-1 (SIRT1/Nrf2/HO-1) pathway. Methods KOA rabbits were constructed and randomly grouped into model group, celecoxib group, low-dose Tanshinone IIA group, high-dose Tanshinone IIA group, and high-dose Tanshinone IIA+SIRT1 inhibitor EX527 group, each consisted of 6 rabbits. Six healthy rabbits were served as the control group. All rabbits were evaluated for behavioral activity. The serum inflammation and oxidative stress factors were measured. HE staining was used to observe the pathological morphology of cartilage tissue, and Mankin scoring was performed. TUNEL staining was performed to measure apoptosis of cartilage cells. Western blot was performed to measure the SIRT1, Nrf2, HO-1, Bcl-2, and Cleaved caspase 3 proteins. Results Compared with the control group, rabbits in the model group showed activity disorders and pathological damage to cartilage tissue, the Mankin score, cartilage cell apoptosis rate, IL-1β IL-6, MDA levels, and Cleaved caspase 3 protein were unusually increased, while IL-10 level, SOD, CAT activities, and SIRT1, Nrf2, HO-1, and Bcl-2 proteins in cartilage tissue were clearly decreased (P<0.05). Compared with the model group, the levels of cartilage tissue damage in rabbits were clearly reduced in the celecoxib group and the low- and high-dose Tanshinone IIA groups, the Mankin score, cartilage cell apoptosis rate, serum inflammatory factors, MDA levels, and Cleaved caspase 3 protein were unusually decreased, while IL-10 level, SOD, CAT activities, and SIRT1, Nrf2, HO-1, and Bcl-2 proteins in cartilage tissue were unusually raised (P<0.05). Compared with the TSA-H group, the cartilage lesions in the TSA-H+EX527 group were more severe, Mankin score, apoptosis rate of cartilage cells, inflammatory response and oxidative stress response were enhanced, Cleaved caspase 3 protein expression was increased, and SIRT1/Nrf-2/HO-1 pathway protein expression in cartilage was decreased (P<0.05). Conclusion TSA may alleviate oxidative stress and inflammatory symptoms, inhibit chondrocyte apoptosis, and improve cartilage tissue damage in KOA rabbits by activating the SIRT1/Nrf2/HO-1 pathway. |