墨旱莲对维甲酸所致大鼠骨质疏松症的药效学研究

目的探讨中药墨旱莲对维甲酸所致大鼠骨质疏松症的药效作用。方法 3月龄SPF级雌性SD大鼠60只,随机分为正常对照组、模型组(RA,75 mg/(kg·d))、墨旱莲组(1.46、0.73、0.37 g/(kg·d))、仙灵骨葆组(1.5 g/(kg·d))。除正常组外,其余各组给予维甲酸造模2 w,造模同时给予墨旱莲、仙灵骨葆。实验过程每日称量体重,连续给药6w后测定血钙(S-Ca)、血磷(S-P)、血清中碱性磷酸酶(ALP)和骨钙素(OCN)的水平,尿液中钙(U-Ca)、磷(U-P)、脱氧吡啶啉(DPD)的水平。采用DXA型骨密度仪检测大鼠的股骨、第4椎骨、胫骨的骨密度(bone mineral density,BMD)。三点弯曲试验检测左侧股骨生物力学性能:最大载荷、结构硬度、能量吸收、最大应力、弹性模量。Micro CT法分析右侧股骨骨微结构。结果墨旱莲1.46 g/(kg·d)能显著升高模型组大鼠的血钙水平,同时降低尿钙、ALP、OCN和DPD(P0.05)水平。与模型组相比,墨旱莲1.46 g/(kg·d)对维甲酸所致骨质疏松大鼠的股骨、第四椎骨及胫骨骨密度分别提高8.17%、11.79%、14.59%(P0.05),对最大载荷、结构硬度、能量吸收、最大应力、弹性模量等生物力学参数分别提高13.98%、16.33%、40.18%、12.45%、34.96%(P0.05),同时能有效抑制维甲酸所致大鼠股骨干骺端骨小梁微结构的退化(P0.05)。结论墨旱莲1.46 g/(kg·d)对维甲酸所致大鼠的骨质疏松症有防治作用,其作用机制可能与增强钙吸收、促进成骨细胞活性、降低骨转换率有关。

Pharmacodynamics of Herba Ecliptae on retinoic acid induced osteoporosis in rats

Objective To investigate the protective effect of Herba Ecliptae on bone in retinoic acid-induced osteoporosis in rats. Methods A total of 60 adult female Sprague-Dawley rats were randomly divided into control group, retinoic acid group (RA, 75mg/(kg?d)), Herba Ecliptae group (1.46, 0.73, 0.37g/(kg?d)) and Xianling Gubao group (1.5g/(kg?d)). All groups except the control group were orally administered with retinoic acid daily, continuous for 14 days. Modeling and administration of Herba Ecliptae and retinoic acid were done at the same time. The body weight of the animals was recorded weekly during the experimental period. After 6 weeks of dosing, calcium (S-Ca), phosphorus (S-P), alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, calcium (U-Ca), phosphorus (U-P) and deoxypyridinoline (DPD) in urine were measured. The bone mineral density (BMD) of the femur, 4th lumbar vertebra and tibia were assayed by Dual Energy X-ray Absorptiometry. The biomechanical properties of left femur were evaluated by three-point bending test and the trabecular microarchitecture of the right femur was measured by MicroCT. Results Administration Herba Ecliptae (1.46 g/(kg?d)) over a 6-week period significantly increased S-Ca level, decreased U-Ca, ALP, OCN and DPD levels in retinoic acid-induced osteoporotic rats (P<0.05). Compared with the model group, Herba Ecliptae (1.46 g/(kg?d)) significantly enhanced the BMD of right femur, 4th lumbar vertebra and tibia, by 10.7, 12.7 and 12.5%, and improved biomechanical properties of Maximum Load, Stiffness, Energy, Maximum Stress and Elastic Modulus by 13.98, 16.33, 40.18, 12.45 and 34.96% (P<0.05). Further, microCT evaluation also showed that Herba Ecliptae (1.46 g/(kg?d)) dramatically promoted trabecular microarchitecture (P <0.05).Conclusion These results suggested that Herba Ecliptae might be a potential medicine for retinoic acid-induced acute osteoporosis, considering that HE can enhance calcium absorption, increase osteoblastic activity and decrease bone turnover rate significantly.