丹皮酚对去卵巢骨质疏松大鼠叉头框蛋白O3a/Wnt 信号通路及 椎骨密度的影响.

BACKGROUND: Paeonol can inhibit inflammation and relieve the clinical symptoms of chronic osteoarthritis. As a natural drug component with less side effects and more safety, it is of great clinical significance to explore the treatment of osteoporosis. OBJECTIVE: To investigate the effects of paeonol on the signal pathway of forkhead box O3a/Wnt and the density of vertebrae in ovariectomized osteoporosis (OVX-OP) rats. METHODS: Female Sprague-Dawley rats were randomly divided six groups (n=10 per group). Rats in the sham operation only underwent removal of adipose tissue adjacent to the ovary, and the other 50 rats were used to make OVX-OP rat models by bilateral ovariectomy. The rat models were randomly divided into OVX-OP group, estrogen group (ethinylestradiol 10 μg/kg/d), low- (paeonol 125 mg/kg/d), medium- (paeonol 250 mg/kg/d), and high-dose (paeonol 500 mg/kg/d) groups. The rats were administered by gavage. Sham operation group and OVX-OP group were given the same amount of normal saline. The intervention lasted for 12 weeks. The levels of serum estrogen, osteoprotegerin and osteocalcin were measured by enzyme-linked immunosorbent assay. Bone mineral density of the femur and vertebrae was measured by dual energy X-ray animal bone mineral density meter. The biomechanical indexes of the femur and vertebrae, elastic modulus, maximum load and yield load, were measured by orthopedic biomechanical tester. The expression levels of forkhead box O3a and Wnt2 mRNA were detected by real-time fluorescence quantitative PCR. The expression levels of forkhead box O3a, Wnt2 and nucleus β-catenin proteins were detected by western blot. RESULTS AND CONCLUSION: After the treatment, the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels, and nucleus β-catenin protein level were significantly lower in the OVX-OP group than the sham operation group (P < 0.05), while serum osteocalcin and vertebral forkhead box O3a mRNA and protein levels were significantly higher in the OVX-OP group (P < 0.05). Compared with the OVX-OP group, low-, medium, and high-dose paeonol significantly increased the bone mineral density, elastic modulus, maximum load, and yield load in the 4th and 5th lumbar vertebrae, serum estradiol and osteoprotegerin levels, Wnt2 mRNA and protein levels in the vertebrae (P < 0.05), and decreased the levels of serum osteocalcin and vertebral FOXO3a mRNA and protein (P < 0.05). Moreover, the above-mentioned indexes were better in the high-dose paeonol group than the estrogen group (P < 0.05). To conclude, paeonol can increase bone mineral density of the vertebrae, improve the biomechanical condition, and relieve osteoporosis in OVX-OP rats, which may be related to the inhibition of forkhead box O3a and the promotion of Wnt2/β-catenin pathway activation. [ABSTRACT FROM AUTHOR]