芪芎通络胶囊对小鼠骨质疏松的改善作用及机制研究

Effect and Mechanism of Qixiong Tongluo Capsules on Osteoporosis in Mice

目的探讨芪芎通络胶囊对维甲酸导致小鼠骨质疏松的改善作用及作用机制。方法按随机数字表法将48只昆明小鼠分为6组,每组8只。除对照组[A组,给予等体积0.5%羧甲基纤维素钠(CMC-Na)]外,其余各组小鼠均于每天7:00给予维甲酸105 mg/kg,持续14 d造模。造模成功后,每天9:00继续给予上述剂量维甲酸,18:00仙灵骨葆组(C组)小鼠灌胃给予仙灵骨葆胶囊1.5 g/kg,芪芎通络胶囊高、中、低剂量组(D1,D2,D3组)给予按生药量计为1.8,0.9,0.45 g/kg的治疗,A组和模型组(B组)小鼠均给予等体积的0.5%CMC-Na。称取小鼠初始体质量和末期体质量,称取胸腺、肝、脾质量,计算脏器指数;测量小鼠股骨湿重、干重、长度和直径;采用试剂盒检测血清钙、血清磷浓度;应用Quantum FX型小动物CT检测股骨密度;计算免疫组化检测股骨中OPG/RANKL蛋白比值的变化。结果与A组相比,B组小鼠体质量、股骨湿重、股骨干重、血清钙含量、骨密度均显著降低(P<0.05),血清磷含量显著升高(P<0.05);与B组相比,各给药组小鼠体质量有升高趋势,C组和D1组小鼠股骨湿重、干重、血清钙含量和骨密度显著升高(P<0.05),C组和D2,D1组小鼠血清磷含量显著降低(P<0.05);免疫组化结果显示,B组小鼠OPG/RANKL蛋白比值显著降低(P<0.05),C组和D1组,D2组,D3组小鼠OPG/RANKL蛋白比值显著升高(P<0.05)。结论芪芎通络胶囊对维甲酸导致的小鼠骨质疏松有改善作用,其作用机制可能与升高OPG/RANKL蛋白表达比值有关。

Objective To investigate the effect and mechanism of Qixiong Tongluo Capsules on osteoporosis induced by retinoic acid in mice.Methods According to the random number table method,48 Kunming mice were divided into 6 groups with 8 mice in each group.In addition to group A[given equal volume of 0.5%sodium carboxymethyl cellulose(CMC-Na)],mice in the other groups were continuously given 105 mg/kg retinoic acid at 7:00 every day for 14 d.After successful modeling,all mice were given 105 mg/kg retinoic acid at 9:00 every day.At 18:00 every day,the mice in Xianlinggubao group(group C)were given 1.5 g/kg Xianlinggubao Capsules by gavage,the high-,medium-and low-dose groups of Qixiong Tongluo Capsules(group D1,D2,D3)were given Qixiong Tongluo Capsules(1.8,0.9,0.45 g/kg according to the crude drug dose),the mice in the control group(group A)and the model group(group B)were given equal volume of 0.5%CMC-Na.The initial and final body weight of mice,the thymus,liver and spleen were weighed and the organ index was calculated.The wet weight,dry weight,length and diameter of femur were measured.The concentrations of calcium and phosphorus in serum were measured by kits.The bone mineral density(BMD)of femur was determined by Quantum FX CT.The ratio of OPG/RANKL protein in femur was detected by immunohistochemistry.Results Compared with group A,the body weight,wet weight,and dry weight of femur,the serum calcium content and BMD in group B were significantly decreased(P<0.05),and the content of serum phosphorus in group B was significantly increased(P<0.05).Compared with group B,the body weight of mice in each treatment group was increased,the wet weight and dry weight of femur,the serum calcium content and BMD of mice in group C and group D1 were significantly increased(P<0.05),and the content of serum phosphorus in group C,group D2 and group D1 was significantly decreased(P<0.05).The results of immunohistochemistry showed that the ratio of OPG/RANKL protein in group B was significantly decreased(P<0.05),while the ratios of OPG/RANKL protein in group C,group D1,group D2 and group D3 were significantly increased(P<0.05).Conclusion Qixiongtongluo Capsules can improve osteoporosis induced by retinoic acid in mice,and its mechanism of action may be related to the increase of the ratio of OPG/RANKL protein expression.