基于Ca2+代谢探讨葛根素治疗骨质疏松症引起心脑血管疾病的药理药效及初步作用机制

Pharmacological efficacy and preliminary mechanism of puerarin for osteoporosis induced cardiovascular diseases based on calcium metabolism

目的观察葛根素对骨质疏松症(OP)引起心脑血管疾病(CD)大鼠的影响,从Ca^2+代谢角度探讨葛根素治疗OP引起CD的药理药效及初步作用机制。方法采用D-半乳糖颈背部注射(1次·d^-1)+地塞米松肌内注射(2次/周)的方法制备OP引起CD大鼠模型,造模成功后,随机分为空白组、模型组、盐酸地尔硫[艹卓]组(21.6 mg·kg^-1)、葛根素组(0.162 g·kg^-1),每组12只,每日灌胃1次,连续灌胃14 d后,采集各组血清样本,分离各组大鼠股骨、血管、心脏等组织。采用HE染色,观察各组大鼠心脏及血管病理学变化情况。采用半自动生化仪检测血清中HDL-C、LDL-C、TG等生化指标的变化;采用ICP-MS法检测股骨、血清、血管以及心脏中Ca^2+含量。结果病理指标及生化指标结果显示,OP引起CD大鼠模型造模成功,葛根素能够改善心脏及血管病理状态,并能调节CD相关生理指标,与模型组相比差异具有统计学意义;ICP-MS结果显示,葛根素治疗后大鼠股骨中Ca^2+含量明显增多,血清、血管、心脏中的Ca2+含量明显减少,与模型组相比差异具有统计学意义。结论葛根素对OP引起的CD有一定的治疗作用,其作用机制可能与调节Ca^2+代谢、抑制"钙搬家"现象有关。

Objective To explore the pharmacological efficacy and preliminary mechanism of puerarin for osteoporosis(OP)induced cardiovascular diseases(CD)in rats based on calcium metabolism.Methods The OP induced CD rat model was established by D-galactose neck back injection(once daily)coupled with dexamethasone intramuscular injection(twice a week).The model rats were randomly divided into 4 groups(n=12)including a blank group,a model group,a positive group(21.6 mg·kg^-1)and a puerarin group(0.162 g·kg^-1).The rats in the positive group and the puerarin group were given treatment medicine once daily for 14 days.The serum samples of each group were collected,and the femur,blood vessels and heart tissues of rats in each group were obtained on the last day of the experiment.HE staining was used to observe the pathological changes of the heart and blood vessels in each group.ELISA kits were used to detect the changes in HDL-C,LDL-C and TG in the serum.ICP-MS was used to detect the content of calciumin all organs.Results The pathological indicators and biochemical indicators showed that OP induced CD model was successfully established.Puerarin ameliorated the pathological state of the heart and blood vessels,and regulated the physiological indicators related to CD,which were significantly different from the model group.ICP-MS results showed that the content of calciumin in the femur was significantly increased after puerarin treatment,and the content of calcium in the serum,the blood vessel and the heart was obviously decreased as compared with that of the model group.Conclusion Puerarin has a significant therapeutic effect on OP induced CD,whose mechanism may be related to the regulation of calcium metabolism and inhibition of"calcium movement".