绝经后骨质疏松症患者外周血中GRP78和ATF4的表达水平及临床意义

Expressions of GRP78 and ATF4 in peripheral blood of postmenopausal patients with osteoporosis and their clinical significance

目的探究绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者外周血中葡萄糖调节蛋白78(glucoseregulated protein 78,GRP78)和激活转录因子4(activating transcription factor 4,ATF4)的水平及临床意义。方法选取2018年12月—2021年5月石家庄市第三医院创伤骨科收治的96例PMO患者为PMO组,另选取同期96名体检健康的绝经女性为正常组。比较PM O组和正常组的一般资料;采用酶联免疫吸附法测定血清GR P78、ATF4水平;利用电化学发光免疫分析仪测定血清β-胶原特殊序列(β-Crosslaps)、Ⅰ型前胶原氨基端前肽(procollagenⅠtype N-terminal propeptide,PINP)水平;利用双能X线骨密度仪检测腰椎骨密度(bone mineral density,BMD);采用Pearson法分析PMO患者血清GRP78、ATF4水平与β-Crosslaps、PIN P、BM D的相关性及PMO患者血清GR P78表达水平与ATF4的相关性;用Logistic回归分析PMO发生的影响因素。结果PMO组患者腰臀比、BMD低于正常组(t=9.76、15.47,P均<0.001);血清GRP78、ATF4、β-Crosslaps、PINP水平高于正常组(t=18.32、16.81、8.15、14.84,P均<0.001);PMO患者血清GRP78、ATF4水平与β-Crosslaps、PINP均呈正相关(r=0.56、0.48、0.48、0.52,P<0.001、<0.001、<0.001、=0.006),与BMD呈负相关(r=-0.54、-0.44,P均<0.001);PMO患者血清GRP78水平与ATF4呈正相关(r=0.595,P<0.001);PINP、GRP78、β-Crosslaps、ATF4是影响PMO发生的危险因素(OR=2.518、2.672、2.271、2.336,P均<0.001),BMD是影响PMO发生的保护因素(OR=0.583,P<0.001)。结论PMO患者血清GRP78、ATF4水平较高,均与β-Crosslaps、PINP、BMD相关,GRP78、ATF4可能是诊治PMO的潜在靶标,测定血清GRP78、ATF4水平有助于临床防治PMO。

Objective To explore the levels and clinical significance of peripheral blood glucose-regulated protein 78(GRP78)and activating transcription factor 4(ATF4)in patients with postmenopausal osteoporosis(PMO).Methods A total of 96 PMO patients admitted to the Third Hospital of Shijiazhuang between December 2018 and May 2021 were selected as the PMO group while another 96 menopausal women confirmed to be healthy by physical examinations served as the normal group.The basic data of the two groups was compared.Enzyme linked immunosorbent assaywas used to measure the serum levels of GRP78 and ATF4 while electrochemiluminescence immunoassay was adopted to measure the serum levels ofβ-Crosslaps and procollagenⅠtype N-terminal propeptide(PINP).The dual-energy X-ray bone densitometer was used to detect lumbar bone mineral density(BMD)while the Pearson method was employed to analyze the correlations between serum levels of GRP78 and ATF4 in PMO patients andβ-Crosslaps,PINP and BMD as well as those between serum levels of GRP78 and ATF4 in PMO patients.Logistic regression was used to analyze the influencing factors of PMO.Results The waist-to-hip ratio and BMD of the PMO group were lower than those in the normal group(t=9.76,15.47,both P<0.001),but the serum levels of GRP78,ATF4,β-Crosslaps and PINP were higher(t=18.32,16.81,8.15,14.84,all P<0.001).The serum levels of GRP78 and ATF4 in PMO patients were positively correlated withβ-Crosslaps and PINP(r=0.56,0.48,0.48,0.52,P<0.001,<0.001,<0.001,=0.006),but negatively with BMD(r=-0.54,-0.44,both P<0.001).The serum level of GRP78 of PMO patients was positively correlated with ATF4(r=0.595,P<0.001).PINP,GRP78,β-Crosslaps and ATF4 were risk factors for PMO(OR=2.518,2.672,2.271,2.336,all P<0.001),while BMD was a protective factor(OR=0.583,P<0.001).Conclusion The serum levels of GRP78 and ATF4 in patients with PMO are relatively high,which are related toβ-Crosslaps,PINP,and BMD.GRP78 and ATF4 may be potential targets for the diagnosis and treatment of PMO.Determination of serum GRP78 and ATF4 levels is helpful for clinical prevention and treatment of PMO.