奥美拉唑对去势大鼠骨密度和骨代谢的影响

目的：观察质子泵抑制剂奥美拉唑对去势雌性大鼠骨密度和骨代谢的影响，为临床合理应用质子泵抑制剂提供依据。方法：8月龄SD雌性大鼠，分成假手术组（Sham+NS组）、假手术给药组（Sham+OMZ组）、去势组（OV+NS组）、去势给药组（OV+OMZ组）。去势组大鼠行去卵巢手术建模，假手术组同等部位切除部分脂肪。给药组大鼠按体质量30 mg·kg^-1·d^-1灌胃奥美拉唑，非给药组按2 mL·d^-1生理盐水灌胃。以双能X线吸收法（DXA）检测骨密度；酶联免疫吸附法检测血清中骨代谢标志物TRAP、CTX-1、PINP、BALP、OC浓度；qRT-PCR法检测股骨骨髓细胞OPG、RANKL、c-FOS、NFATc1的mRNA表达水平以及R/O值。结果：去势组较假手术组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高，去势给药组较去势组骨密度降低、TRAP、CTX-1、PINP、OC浓度升高、R/O值升高。结论：质子泵抑制剂奥美拉唑可能诱导去势雌性大鼠体内的RANKL表达量相对增加，R/O值升高，进而通过OPG/RANK/RANKL信号通路使得破骨细胞活动相对增强，骨吸收代谢加快，加速骨质疏松进程。

Effects of omeprazole on bone mineral density and bone metabolism in ovariectomized rats

OBJECTIVE To observe the effect of omeprazole, a proton pump inhibitor, on bone mineral density and bone metabolism in ovariectomized female rats, and to provide evidence for rational use of proton pump inhibitors in clinic. METHODS Female SD rats of 8 months old were divided as follows:Sham+NS group, Sham+OMZ group, OV+NS group, OV+OMZ group. Modeling:Ovariectomy was performed in OV group rats, and part of the fat was removed at the same site in the Sham group. Drug administration:Rats in the administration group were orally administered at a body weight of 30 mg·kg^-1·d^-1, 2 mL normal saline(NS) was administered to the non-administration group. Index:Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA); serum levels of bone metabolic markers TRAP, CTX-1, PINP, BALP and OC were detected by enzyme-linked immunosorbent assay (ELISA); and the expression levels of OPG, RANKL, c-FOS, NFATc 1 and R/O in femoral bone marrow cells were detected by qRT-PCR. RESULTS Compared with Sham+NS group, OV+NS group had lower BMD, higher TRAP, CTX-1, PINP, OC concentration and R/O value, while OV+OMZ group had lower BMD, higher TRAP, CTX-1, PINP, OC concentration and R/O value than OV+NS group. CONCLUSION Omeprazole may induce a relative increase in the expression level of RANKL and an increase in the R/O value in the ovariectomized rats, thereby enhancing the osteoclast activity through the OPG/RANK/RANKL signaling pathway, speed up bone resorption metabolism, and finially accelerate the osteoporosis process.