维生素K2对维甲酸致大鼠骨质疏松症的抑制作用

The inhibitory effect of vitamin K2 on osteoporosis induced by tretinoin in growing female rats

目的 比较VitK2（20）、K2（35）和柠檬酸-苹果酸钙（CCM）对维甲酸致大鼠骨质疏松症的抑制作用.方法 取60只3月龄雌性大鼠随机均分为正常对照组、模型组、1 mg/kg Vit K2（20）组、0.01 mg/kg Vit K2（35）组、100 mg/kg CCM组和0.125 mg/kg的尼尔雌醇（nilestriol）片阳性对照组.正常对照组以二次蒸馏水10 ml＊kg-1＊d-1灌胃,其余组按维甲酸70 mg＊kg-1＊d-1灌胃共15 d,从第9天起上午灌服维甲酸,下午分别灌服VitK2（20）、K2（35）、CCM和尼尔雌醇,灌胃量均为10 ml＊kg-1＊d-1,连续14 d.结果 与模型组比较,1 mg/kg VitK2（20）, 0.01 mg/kg K2（35）和100 mg/kg CCM灌胃给药14 d可明显提高大鼠血清钙含量,显著升高股骨骨密度,并且骨密度与股骨灰重呈线性相关,其中VitK2（35）组的子宫指数、卵巢指数均明显高于其他药物组（P〈0.05）;VitK2组骨小梁厚度增加,表面积百分率明显增大,VitK2（35）组的骺板软骨细胞增生明显且有许多新的骨小梁形成.结论 VitK2（20）、K2（35）和CCM对维甲酸致大鼠的骨质疏松症有明显抑制作用,在同等剂量下,VitK2活性约为CCM的102～104倍,VitK2（35）尤为显著.

Abstract： Objective To investigate the inhibitory effects of vitamin K2 （20）, K2 （35） and calcium citrate malate （CCM） on osteoporosis induced by tretinoin in growing female rats. Methods Sixty three month old female rats were randomly divided into normal group, model group, Vitamin K2 （20） group, Vitamin I（2 （ 35 ） group, CCM group and nilestriol group. The normal group received 10 ml·kg^-1· d^-1 of second distilled water, the other five groups received 70 mg·kg^-1· d^-1 of tretinoin for 15 days, from the ninth day, respectively received additional drugs of 1 mg/kg K2 （20）, 0.01 mg/kg K2 （35）, 100 mg/kg CCM and 0. 125 mg/kg nilestriol in the afternoon for 14 days. Results The femur bone mineral density（BMD） and the serum level of Ca^2＋ was significantly increased in Vit K2 groups and CCM group compared with the model group, while the femur BMD had a positive linear correlation with its bone ash weight, the index of ovarian and uterine of Vit K2 （35） group were significantly higher than other drug groups. Trabecular thickness and percentage of trabecular area in Vit K2 groups were significantly increased more than that of the osteoporotic model, particularly, epiphyseal cartilage cells hyperplasia was very obvious and many new bone trabecular was formed in VitK2 （35）group. Conclusion Vitamin K2 （20）, K2 （35） and CCM all have the inhibitory effect on osteoporosis induced by tretinoin, Vit K2 especially K2 （35） is about 102- 104 times more potent than the traditional agents CCM at the same dose.