埃索美拉唑对雄性大鼠骨密度及骨代谢的影响

The effect of esomeprazole use to bone mineral density and bone metabolism of male rats

目的 观察不同剂量的埃索美拉唑在不同时间点对雄性SD大鼠骨密度及骨代谢的影响。方法 将24只3个月龄雄性SD大鼠按体质量随机分为对照组（给予赋形剂）、小剂量组[按10 mg/（kg·d）的剂量给予埃索美拉唑]和大剂量组[按50 mg/（kg·d）的剂量给予埃索美拉唑]。第0、8、14周时,检测每只大鼠全身骨密度及血清中骨碱性磷酸酶、抗酒石酸酸性磷酸酶和钙的浓度。处死大鼠后用组织形态学方法评估大鼠股骨结构改变。结果 与对照组比较,大剂量组中大鼠体质量增长明显受抑制（P〈0.05）,第14周时骨密度明显降低,血清中骨碱性磷酸酶、抗酒石酸酸性磷酸酶和钙的浓度明显升高,分别为（198.51±6.98）、（1.49±0.04）U/L、（2.44±0.05）mmol/L,而第8周时3组间差异无统计学意义（P〈0.05）。组织形态学显示14周时3组间的股骨结构差异明显,大剂量组空骨陷窝率明显高于对照组和小剂量组（P〈0.05）。结论 大剂量应用埃索美拉唑导致雄性大鼠骨密度降低并影响其骨代谢,这种效应还存在一定的时间依赖性。

Objective This study aimed to investigate the effects of different doses of esome- prazole use of male SD rats bone mineral density and bone metabolism at different time points in order to guide clinical treatment. Methods Twenty four 3-month-old male rats were divided into three groups ： the control group received the vehicle only, the low-dose esomeprazole group was treated with esomeprazole of 10 mg/ （kg·d） and the high-dose esomeprazole group was treated with esomeprazole of 50 mg （kg· d）. We assess total bone mineral densities （BMDs） and bone alkaline phosphatase （B-ALP）, tartate resistant acid phosphatase 5b （TRACP 5b） and serum calcium concentration at weeks 0, 8 and 14. Bone histomorphometric analysis was performed to evaluate the structural changes in the femur of rats after sacrifice. Resuits The body weight of the high-dose esomeprazole group was suppressed whereas that of the control group increased significantly at week 8 （P 〈 0. 05）. The BMD of the high-dose group decreased dramatic- ally whereas that of the other two groups increased significantly at week 14. Serum B-ALP, TRACP 5b and calcium concentrations increased significantly which is （ 198.51 ± 6. 98 ）, （ 1.49 ± 0. 04 ） U/L and （2.44 ± 0. 05） mmol/L respectively. Significant changes in the results were not observed at week 8 （P 〉 0.05）. Bone histomorphometric analysis showed significantly different bone structures among the three groups at week 14 and the ER of the high-dose group was significantly higher than the control group and the low-dose group. Conclusion Long term and high dose use of esomeprazole reduces bone mineral density and effects bone metabolism of male rats in a time-dependent manner.