阿托伐他汀对激素性股骨头坏死大鼠的作用及对Wnt/β-catenin信号通路的影响

Effect of atorvastatin on steroid-induced osteonecrosis of the femoral head and the Wnt/β-catenin signaling pathway in rats

摘要:

目的 探究阿托伐他汀对激素性股骨头坏死大鼠的作用及对果蝇无翅基因/β-连环蛋白（Wnt/β-catenin）信号通路的影响。方法 30只SD雄性大鼠随机分为对照组、模型组及阿托伐他汀组，每组10只。模型组和阿托伐他汀组复制激素性股骨头坏死模型并对每只大鼠腹腔注射醋酸泼尼松龙（24.5 mg/kg）和青霉素钠（8万u），2次/周，连续给药6周，共18只大鼠模型复制成功。模型复制的同时，阿托伐他汀组腹腔注射阿托伐他汀1 mg/（kg·d），对照组与模型组给予等量的生理盐水，连续治疗6周后，检测各组大鼠血清钙（S-Ca）、血清磷（S-P）水平，以及血清碱性磷酸酶（ALP）、转化生长因子β₁（TGF-β₁）水平；比较大鼠骨组织ALP、TGF-β₁ mRNA相对表达量；比较大鼠骨组织Wnt1、β-catenin蛋白的表达。结果 与对照组比较，模型组大鼠血清S-Ca、S-P及TGF-β1水平降低（P <0.05），ALP水平升高（P <0.05），ALP mRNA相对表达量升高（P <0.05），TGF-β₁ mRNA相对表达量降低（P <0.05），Wnt1水平和β-catenin蛋白相对表达量下降（P <0.05）；与模型组比较，阿托伐他汀组大鼠血清S-Ca、S-P及TGF-β₁水平升高（P <0.05），ALP水平降低（P <0.05），ALP mRNA相对表达量下降（P <0.05），TGF-β₁ mRNA相对表达量升高（P <0.05），Wnt1水平和β-catenin蛋白相对表达量升高（P <0.05）。结论 阿托伐他汀能够改善激素性股骨头坏死大鼠骨代谢指标，其机制可能与Wnt/β-catenin信号通路有关。

Abstract:

Objective To explore the effects of atorvastatin on steroid-induced femoral head necrosis and the Wnt/β-catenin signaling pathway in rats.Methods Thirty male SD rats were randomly divided into control group, model group and atorvastatin group, with 10 in each group. The steroid-induced osteonecrosis of the femoral head models were established with rats in the model and atorvastatin groups via intraperitoneal injection with 24.5 mg/kg of prednisolone acetate and 80,000 units of penicillin sodium twice a week for consecutive 6 weeks. The rats in the control group were given the equal volume of normal saline and penicillin sodium. A total of 18 rats were successfully modelled. After 6 weeks of continuous treatments, the serum levels of calcium (S-Ca), phosphorus (S-P), alkaline phosphatase (ALP) and transforming growth factor β1 (TGF-β₁) in the rats were detected. The relative mRNA expressions of ALP and TGF-β₁ and the relative protein expressions of Wnt and β-catenin in the femoral head were compared.Results Compared with the control group, the levels of S-Ca, S-P and TGF-β₁ were decreased, the level of ALP was increased, the mRNA expression of ALP was up-regulated, and the mRNA expression of TGF-β1 and the protein expressions of Wnt1 and β-catenin were down-regulated in the model group (P < 0.05). Compared with the model group, the levels of S-Ca, S-P and TGF-β₁ were increased, the level of ALP was decreased, the mRNA expression of ALP was down-regulated, and the mRNA expression of TGF-β₁ and protein expressions of Wnt and β-catenin were up-regulated in the atorvastatin group (P < 0.05).Conclusions Atorvastatin can improve bone metabolism indexes in rats with steroid-induced osteonecrosis of the femoral head, and its mechanism may be related to the Wnt/β-catenin signaling pathway.