蛇床子素对绝经后骨质疏松症大鼠骨代谢的调节作用及机制

目的 探究蛇床子素对绝经后骨质疏松症(postmenopausal osteoporosis,PMO)模型大鼠骨代谢生化指标及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)通路的影响.方法 选取90只雌性大鼠,采用随机数字表法将大鼠分为:健康对照组、模型组、雌二醇组和蛇床子素低、中、高剂量组,每组15只.除健康对照...

Regulation effect and mechanism of osthole on bone metabolism in rats with postmenopausal osteoporosis

Objective To explore the effects of osthole on biochemical indexes of bone metabolism and phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) pathway in model rats with postmenopausal osteoporosis (PMO). Methods Ninety female rats were enrolled and divided into healthy control group, model group, estradiol group, low-dose, medium-dose, and high-dose osthole groups by random number table method, with 15 cases in each group. Except for healthy control group, bilateral ovaries were removed to prepare PMO rat model. Rats in estradiol group received 0.21 mg/kg of estradiol intragastrically. Rats in low-dose, medium-dose, and high-dose osthole groups received 10, 20, or 40 mg/kg of osthole intragastrically, respectively. After 12-week treatment, the serum levels of anti-tartrate acid phosphatase-5b (TRAP-5b), osteocalcin (OC), and alkaline phosphatase (ALP), urine calcium, phosphorus, creatinine, and deoxypyridinoline (D-Pry) in each group were detected. The systemic bone mineral density (BMD) was measured after 8 and 12 weeks of treatment. BMD of the left femur and lumbar vertebra, and biomechanical properties of the right femur and the fourth lumbar vertebra were detected after 12 weeks of treatment. The relative expression levels of PI3K/AKT pathway-related proteins were detected with Western blotting. Results Compared to those in healthy control group, levels of TRAP-5b, urine calcium/creatinine, urine phosphorus/creatinine, and D-Pry increased significantly (P<0.05), while OC, ALP, systemic BMD, BMD of the isolated femur and vertebrae, elastic modulus and maximum load of the femur, elastic modulus and maximum loads of the lumbar vertebrae, levels of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) and phosphorylated phosphoinositide-3 kinase/phosphoinositide-3 kinase (p-PI3K/PI3K) decreased significantly in the model group (P<0.05). Compared to those in estradiol group, levels of TRAP-5b, urine calcium/creatinine, urine phosphorus/creatinine, and D-Pry increased significantly (P<0.05), while OC, ALP, systemic BMD, BMD of the isolated femur and vertebrae, elastic modulus and maximum load of the femur and lumbar vertebrae, levels of p-AKT/AKT and p-PI3K/PI3K decreased significantly in low-dose, medium-dose, and high-dose osthole groups (P<0.05). Compared to those in model group, levels of TRAP-5b, urine calcium/creatinine, urine phosphorus/creatinine and D-Pry decreased significantly in low-dose, medium-dose, and high-dose osthole groups (P<0.05), but they gradually decreased with the increase of usage dosage (P<0.05). OC, ALP, systemic BMD, BMD of the isolated femur and vertebrae, elastic modulus and maximum load of the femur, elastic modulus and maximum loads of the lumbar vertebrae, levels of p-AKT/AKT and p-PI3K/PI3K increased significantly (P<0.05), and they gradually increased with the increase of usage dosage (P<0.05). Conclusion Osthole improves bone metabolism and increase BMD with a dose-dependent manner in PMO rats. The action mechanism is related to the activating of PI3K/AKT signaling pathway.