蕊花糖苷与99Tc-MDP联合治疗糖皮质激素诱导大鼠骨质疏松的效果及其分子机制研究
Therapeutic effect and molecular mechanism of Verbascoside combined with 99Tc-MDP on glucocorticoid-induced osteoporosis in rats
投稿时间:2018-12-26  修订日期:2019-03-21
DOI:
中文关键词:  毛蕊花糖苷  99Tc-MDP  糖皮质激素  骨质疏松  USP10  FLT3
英文关键词:verbascoside  99Tc-MDP  glucocorticoid  osteoporosis  USP10  FLT3
基金项目:
作者单位邮编
孙玉兰* 大连市友谊医院 116000
刁云鹏 大连医科大学 
孙伟 大连市友谊医院 
王琳 大连市友谊医院 
李禾 大连市友谊医院 
李淼 大连市友谊医院 
王萍 大连市友谊医院 
冯英霞 大连市友谊医院 
徐岩 大连市友谊医院 
宫宇 大连市友谊医院 
王青 大连市友谊医院 
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中文摘要:
      摘 要 目的:探索毛蕊花糖苷(verbascoside, Ver) 联合99Tc-亚甲基二磷酸盐(99-Technetium-methylene diphosphonate,99Tc-MDP)对糖皮质激素诱导大鼠骨质疏松(glucocorticoid-induced osteoporosis, GIO)的治疗作用,及其分子机制。 方法:SD大鼠连续8周肌肉注射地塞米松(Dexamethasone,Dex)磷酸钠(1mg/kg,1周2次)建立GIO模型。Dex造模同时,Ver组、联合组、99Tc-MDP组、模型组大鼠分别给与Ver(30mg/kg)、联合99Tc-MDP(5mg/kg)、Ver联合99Tc-MDP(5mg/kg)、生理盐水,对照组大鼠不予造模。给药8周后检测相关指标。 结果:与对照组相比较,模型组的大鼠的体重、股骨干重明显降低,骨代谢相关血液指标明显异常;双能X线吸收法(dual-energy X-ray absorption,DEXA)结果显示:模型组的大鼠全身、腰椎体及股骨骨密度均明显降低;股骨三点弯曲实验最大载荷、弹性载荷、弹性位移及弹性模量等参数也都明显降低;进一步RT-PCR结果显示,模型组骨组织中USP10及FLT3表达明显高于对照组。而毛蕊花糖苷及联合99Tc-MDP治疗均明显改善上述症状。进一步研究发现毛蕊花糖苷组和联合用药组的USP10/FLT3表达明显低于99Tc-MDP组及模型组,而99Tc-MDP组与模型组之间的表达无明显差异。 结论:毛蕊花糖苷可以抑制大鼠骨组织USP10/FLT3通路的活性,进而改善GIO;毛蕊花糖苷和99Tc-MDP治疗GIO大鼠具有良好的药理协同作用,并且是通过作用不同的分子靶点而完成的。
英文摘要:
      Abstract Objective: To explore the therapeutic effect of verbascoside (Ver) combined with 99Tc-methylenediphosphate (99Tc-MDP) on glucocorticoid-induced osteoporosis (GIO), in rats and its molecular mechanism. Methods: SD rats were injected Dexamethasone (Dex ) sodium phosphate ( 1mg/kg, twice a week ) intramuscularly for 8 weeks to establish GIO model. After GIO model was established, rats in Ver group, combined group, 99Tc-MDP group and model group were given Ver(30mg/kg ), Ver combined 99Tc-MDP(5mg/kg ) 99Tc-MDP(5mg/kg) and normal saline respectively, while rats in the control group were not modeled. The related indexes were detected after 8 weeks of administration. Results: Compared with the control group, the body weight and weight of the femoral shaft in the model group were significantly reduced, and the blood indexes related to bone metabolism were obviously abnormal. The results of dual-energy X-ray absorption (DEXA) showed that the bone mineral density of the whole body, lumbar spine and femur in the model group all decreased significantly. The maximum load, elastic load, elastic displacement and elastic modulus of the three-point bending test of the femur were also significantly reduced. However, both Ver and 99Tc-MDP treatment significantly improved the above symptoms. Further Western blot results showed that USP10 and FLT3 expression in the bone tissue of model group was significantly higher than that of control group. USP10/FLT3 expression in the Ver group and the combination group was significantly lower than that in the 99Tc-MDP group and the model group, but there was no significant difference between the 99Tc-MDP group and the model group. Conclusion: Ver can inhibit the activity of USP10/FLT3 pathway in rat bone tissue and improve GIO;Ver and 99Tc-MDP have a good pharmacological synergistic effect in treating GIO rats, and are accomplished by acting on different molecular targets.
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