关键词: 激素性股骨头坏死, 黄芩素, 破骨细胞, 细胞凋亡, 氧化应激

Abstract: BACKGROUND: The development of steroid-induced osteonecrosis of the femoral head is a complex process involving multiple mechanisms. There is still no standard therapeutic drug for early intervention of this disease. Current studies have shown that baicalein has various pharmacological activities such as regulating lipid metabolism, bone metabolism, apoptosis and anti-oxidative stress, which provides an idea for the prevention and treatment of steroid-induced osteonecrosis of the femoral head.
OBJECTIVE: To observe the preventive effect of baicalein against steroid-induced osteonecrosis of the femoral head and to investigate its possible mechanism.
METHODS: Thirty-six 10-week-old male Sprague-Dawley rats were randomly divided into three groups (n=12 per group): blank control group, model group, and baicalein intervention group. In the model group and baicalein intervention group, intraperitoneal lipopolysaccharide and intramuscular injection of methylprednisolone sodium succinate were performed for modeling, while normal saline was used as a substitute for the modeling drug in the blank control group. Baicalein 300 mg/kg was administered by gavage (once a day for 6 weeks) at the time of initial intramuscular glucocorticoid injection in the baicalein intervention group, and baicalein was replaced by normal saline in the other two groups. The serum level of malondialdehyde in rats was detected at 2 weeks of the experiment. Blood lipid indicators and bone formation metabolic markers were detected at 6 weeks of the experiment, the histomorphometric changes of the femoral head were analyzed by hematoxylin-eosin staining, anti-tartaric acid phosphatase staining and TUNEL staining, and the femoral head was subjected to Micro-CT scanning and three-dimensional reconstruction of the bone in order to analyze the alterations of bone tissue structure and parameters.
RESULTS AND CONCLUSION: The serum levels of malondialdehyde, triglyceride, β-collagen type I carboxy-terminal peptide were increased and the serum levels of bone specific alkaline phosphatase and pre-collagen type I amino-terminal peptide were decreased in the model group compared with the blank control group (P < 0.05). The serum level of malondialdehyde decreased in the baicalein intervention group compared with the model group (P < 0.05), but there was no significant difference between the baicalein intervention group and blank control group (P > 0.05). The serum level of triglyceride was higher in the baicalein intervention group than the blank control group (P < 0.05), but had no significant difference between the baicalein intervention group and model group (P > 0.05). There were also no significant differences in the levels of bone specific alkaline phosphatase and β-collagen type I carboxy-terminal peptide between the baicalein intervention group and the other two groups (P > 0.05). The serum level of the baicalein intervention group was lower in the baicalein intervention group than the blank control group (P < 0.05) but had no significant difference between the baicalein intervention group and model group (P > 0.05). Histomorphological analysis of the femoral head showed that the rate of bone empty lacuna, osteoclast counting and cell apoptosis rate in the femoral head of model group rats were significantly higher than those of the other two groups (P < 0.05). There was a significant increase in the number of adipocytes in the bone marrow cavity of the femoral head, bone trabeculae were thinned and sparsely arranged with more disruptions in the continuity. The incidence of osteonecrosis was higher in the model group (75%) than in the baicalein intervention group (25%; bilateral and unilateral exact significance results were both 0.05). There was also an increase in the number of adipocytes in the bone marrow cavity of the femoral head in the baicalein intervention group, and the trabecular changes were roughly similar to those in the model group. Micro-CT results showed that bone volume fraction, trabecular thickness, trabecular number, and bone mineral density decreased and trabecular separation increased in the model group compared with the blank control group (P < 0.05). Overall significant bone mass loss was observed in the model group. Bone tissue parameters in the baicalein intervention group were significantly improved than those in the model group, which were reflected in bone volume fraction, trabecular thickness and trabecular separation (P < 0.05), and trabecular number and bone mineral density had no significant difference between the baicalein intervention group and blank control group (P > 0.05). Although baicalein failed to significantly ameliorate dyslipidemia and promote bone formation in rats with steroid-induced osteonecrosis of the femoral head, it could reduce the incidence of steroid-induced osteonecrosis of the femoral head by reducing oxidative stress damage, decreasing cell apoptosis, inhibiting osteoclasts, suggesting its effectiveness in the early prevention of steroid-induced osteonecrosis of the femoral head.

Key words: steroid-induced osteonecrosis of the femoral head, baicalein, osteoclast, cell apoptosis, oxidative stress