杜仲提取物改善抑郁小鼠的骨代谢机制研究

目的探讨杜仲提取物改善抑郁小鼠的骨代谢机制。方法用慢性温和不可预见性刺激结合孤养方法建立抑郁症小鼠模型。按照体重将小鼠随机分为4组:正常组、模型组和低、高2个剂量实验组,每组10只;造模后第21天开始给药,低、高2个剂量实验组分别灌胃给予杜仲提取物20,40 mg·kg^-1(均3 mL),正常组和模型组给予等量的0.9%NaCl,1次/天,连续4周。以双能X线骨密度检测仪检测小鼠骨密度(BMD);以酶联免疫吸附法检测血清骨代谢相关指标;以免疫印迹法检测L5骨组织中磷酸化c-Jun氨基末端激酶(p-JNK)和磷酸化AP1(p-AP1)蛋白相对表达水平。结果正常组、模型组和低、高2个剂量实验组的小鼠骨BMD分别为(0.48±0.01),(0.39±0.02),(0.41±0.01)和(0.43±0.01)g·cm^-2;这4组骨组织中p-JNK蛋白相对表达量分别为0.97±0.05,2.44±0.08,1.99±0.04和1.58±0.03;这4组骨组织中p-AP1蛋白相对表达量分别为0.96±0.04,3.13±0.03,2.75±0.06和2.22±0.08。上述指标:模型组与正常组比较,差异均有统计学意义(均P<0.05);2个剂量实验组与模型组比较,差异均有统计学意义(均P<0.05)。结论杜仲提取物可能通过降低JNK、AP1磷酸化水平,发挥对抑郁症小鼠骨骼的保护作用。

Study on the improving and mechanism of eucommia ulmoides extract on bone metabolism in depressed mice

Objective To investigate the improving and mechanism of eucommia ulmoides extract on the bone metabolism in depressed mice. Methods The depression mouse model was established by chronic mild and unpredictable stimulation combined with solitary feeding. The mice were randomly divided into 4 groups according by weight:normal group, model group and low and high dose experimental groups,with 10 mice in each group. The drug was administered on the 21 st day after modeling. The low and high dose experimental groups were given 20,40 mg·kg^-1 eucommia ulmocha extract by gavage(3 mL);the normal group and the model group were given the same amount of normal saline,once a day for 4 weeks. The bone density(BMD) of mice was detected by dual-energy X-ray bone density detector. Serum bone metabolism related indexes were detected by enzyme-linked immunosorbent assay. The relative expression levels of phosphorylated c-Jun N-terminal kinase protein(p-JNK)and phosphorylated AP1(p-AP1)protein in L5 bone tissue were detected by Western blot. Results BMD in normal group, model group and low and high dose experimental groups were(0.48±0.01),( 0. 39 ± 0. 02),( 0. 41 ± 0. 01) and( 0. 43 ± 0. 01) g·cm^-2,respectively;the relative expression of p-JNK protein in bone tissues of the four groups were 0. 97 ± 0. 05,2. 44 ± 0. 08,1. 99 ± 0. 04 and 1. 58 ± 0. 03,respectively;the p-AP1 protein in bone tissues of the four groups were 0. 96 ± 0. 04,3. 13 ± 0. 03,2. 75 ± 0. 06 and 2. 22 ± 0. 08,respectively. Comparison between model group and normal group,the difference of the indicators were statistically significant( all P < 0. 05);comparison between two doses of experimental groups and model group,the difference of the indicators were statistically significant( all P < 0. 05). Conclusion Extracts of eucha ulmoides may protect the bones of depressed mice by reducing the phosphorylation levels of JNK and AP1.