雷公藤甲素通过抑制破骨细胞生成预防骨丢失的研究

Triptolide prevents bone loss by inhibiting osteoclastogenesis

目的探讨雷公藤甲素抗骨质疏松的作用及机制。方法建立大鼠老年性骨质疏松模型。40只22月龄雄性SD大鼠随机分为雷公藤甲素(每天15μg/kg腹腔注射)治疗组和生理盐水对照组(每天15μg/kg腹腔注射),连续8周。采用显微CT分析胫骨近端骨松质的骨密度(BMD)和骨显微结构。WB检测成骨相关蛋白表达水平。TRACP-5b染色法测定破骨细胞数,同时检测骨吸收标志物表达水平。结果显微CT结果显示,雷公藤甲素治疗组大鼠骨密度、骨体积/总体积比值(Bv/Tv)、骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)、骨小梁间距(Tb.Sp)均显著高于对照组(P<0.05)。两组的成骨相关蛋白表达水平无明显差异,TRACP-5b染色显示雷公藤甲素减少了体内破骨细胞的数量(P<0.05),同时血液骨吸收标志物水平也明显降低(P<0.05)。结论雷公藤甲素通过抑制破骨细胞生成进而对老年性骨质疏松有保护作用。雷公藤甲素可能是治疗老年性骨质疏松症的一种可行方案。

Objective To investigate the antiosteoporotic effect and mechanism of triptolide.Methods A rat model of senile osteoporosis was established.Forty 22-month-old male SD rats were randomly divided into a treatment group of triptolide(15μg/kg per day intraperitoneally)and a control group of saline(15μg/kg per day intraperitoneally)for 8 weeks treatment.Bone mineral density(BMD)and bone microstructure of the proximal tibial cancellous were analyzed by micro-CT.Western blot was used to detect the expression level of osteogenic-related proteins.The number of osteoclasts was measured by TRACP-5b staining,and the expression levels of bone resorption markers were also detected.Results Micro-CT results showed that BMD,bone volume/total volume ratio(Bv/Tv),bone trabecular thickness(Tb.Th),bone trabecular number(Tb.N),and bone trabecular spacing(Tb.Sp)in the rats treated with ryanodine were significantly higher than those in the control group(P<0.05).There was no significant difference in osteogenesis-related protein expression between the two groups,and TRACP staining result showed that triptolide reduced the number of osteoclasts in vivo(P<0.05),while blood bone resorption marker levels were also significantly lower(P<0.05).Conclusions Triptolide has a protective effect on age-related osteoporosis by inhibiting osteoclastogenesis.Which may be a feasible option for the treatment of senile osteoporosis.