孫 建, 房義輝, 柳 達

·臨床論著·

老年女性骨質(zhì)疏松患者血清IGF-1和ET-1水平變化的意義

孫 建1, 房義輝1, 柳 達2

目的 探討老年女性骨質(zhì)疏松患者血清胰島素樣生長因子-1(IGF-1)和內(nèi)皮素-1(ET-1)水平變化的意義。方法 選取93例老年女性骨質(zhì)疏松患者作為病例組,并選取同期50例老年女性健康者作為對照組。采用ELISA法檢測血清IGF-1和ET-1水平及骨代謝指標；采用雙能X線骨密度(BMD)測量儀對每位研究對象L1～4椎體處和股骨頸的BMD進行檢測。采用Pearson相關(guān)分析對變量間相關(guān)關(guān)系進行分析。結(jié)果 病例組IGF-1、骨鈣素(BGP)、骨堿性磷酸酶(BAP)和BMD水平均低于對照組,而ET-1、Ⅰ型膠原交聯(lián)羧基端肽(CTX-1)和抗酒石酸酸性磷酸酶5b(TRACP-5b)水平均高于對照組,差異均有統(tǒng)計學意義(P<0.001)。Pearson相關(guān)分析顯示,病例組血清IGF-1水平與ET-1、CTX-1和TRACP-5b呈負相關(guān)(P<0.05),而與BGP、BAP和BMD呈正相關(guān)(P<0.05)；病例組血清ET-1水平與BGP、BAP和BMD呈負相關(guān)(P<0.05),而與CTX-1和TRACP-5b呈正相關(guān)(P<0.05)。結(jié)論 老年女性骨質(zhì)疏松患者血清IGF-1水平降低而ET-1水平升高,且與BMD和骨代謝指標密切相關(guān),可能共同參與了骨質(zhì)疏松發(fā)病過程。

老年人;女性;骨質(zhì)疏松;胰島素樣生長因子-1;內(nèi)皮素-1

隨著我國人口老齡化加劇,骨質(zhì)疏松的患病率呈逐年上升趨勢;骨質(zhì)疏松成為患者骨折甚至死亡的重要原因,其中老年女性占了絕大部分,這嚴重影響老年女性的健康[1]。目前,老年女性發(fā)生骨質(zhì)疏松的發(fā)病機制尚未研究清楚。胰島素樣生長因子-1(IGF-1)作為骨骼中含量較多的生長因子,在調(diào)控破骨細胞增殖和分化、骨細胞功能、骨代謝等方面發(fā)揮重要作用[2],研究表明[3]IGF-1可能與骨質(zhì)疏松發(fā)生過程密切相關(guān)。內(nèi)皮素-1(ET-1)作為縮血管多肽,與血管內(nèi)皮細胞增殖密切相關(guān)[4],研究表明[5]雌激素水平可影響ET-1生物活性而導(dǎo)致微循環(huán)血管功能紊亂。筆者選取2013年2月～2015年3月在我院就診的93例老年女性骨質(zhì)疏松患者作為研究對象,分析患者血清中IGF-1和ET-1水平變化,探討兩者與骨代謝指標之間的關(guān)系,報道如下。

1 材料與方法

1.1 病例與對照資料 病例組93例,年齡65～79(70.4±5.3)歲?；颊呔蟇HO推薦的骨質(zhì)疏松診斷標準。排除標準:① 甲狀腺、甲狀旁腺、糖尿病等內(nèi)分泌系統(tǒng)疾病者；② 心、肝、腎等重要臟器功能障礙者；③ 惡性腫瘤者；④ 6個月內(nèi)有服用鈣劑、Vit D、肝素及激素類藥物者。同期,招募在我院進行健康體檢≥65歲的老年女性健康志愿者,均排除骨質(zhì)疏松及其他骨科疾病,其他排除標準同病例組,最終入選50例作為對照組,年齡65～81(71.2±5.7)歲。本研究通過醫(yī)院倫理委員會批準,病例組和對照組人員均知情同意。

1.2 方法

1.2.1 血清IGF-1和ET-1水平及骨代謝指標檢測 研究對象均抽取晨起空腹靜脈血6 ml,3 500 r/min離心15 min,留取血清,保存于-70℃冰箱備檢。采用ST-360自動多功能酶標儀(上?？迫A公司),ELISA法檢測血清IGF-1和ET-1水平,以及骨代謝指標骨鈣素(BGP)、骨堿性磷酸酶(BAP)、Ⅰ型膠原交聯(lián)羧基端肽(CTX-1)和抗酒石酸酸性磷酸酶5b(TRACP-5b)指標。人IGF-1和ET-1檢測試劑盒均購自上海常斤生物科技有限公司,BGP、BAP、CTX-1和TRACP-5b檢測試劑盒均購自上海研生生化試劑有限公司。實驗均在標準條件下按照試劑盒操作說明進行。

1.2.2 骨密度(BMD)檢測 用雙能X線BMD測量儀(美國GE公司)對每位研究對象L1～4椎體處和股骨頸(左側(cè))的BMD進行檢測。參照WHO的標準,骨量正常:T值>-1.0 SD；骨量減少:-2.5 SD

2 結(jié)果

2.1 兩組一般資料比較 見表1。年齡、絕經(jīng)時間、體重、體重指數(shù)和高血壓比例兩組比較差異無統(tǒng)計學意義(P>0.05)。

2.2 兩組血清IGF-1和ET-1水平及骨代謝指標比較 見表2。IGF-1、BGP、BAP和BMD病例組水平均低于對照組,ET-1、CTX-1和TRACP-5b水平病例組均高于對照組,各項比較差異均有統(tǒng)計學意義(P<0.001)。

2.3 病例組血清IGF-1和ET-1水平與骨代謝指標相關(guān)性 見表3。Pearson相關(guān)分析顯示,病例組血清IGF-1水平與ET-1、CTX-1和TRACP-5b呈負相關(guān)(P<0.05),而與BGP、BAP和BMD呈正相關(guān)(P<0.05)；病例組血清ET-1水平與BGP、BAP和BMD呈負相關(guān)(P<0.05),而與CTX-1和TRACP-5b呈正相關(guān)(P<0.05)。

3 討論

3.1 骨代謝指標與骨質(zhì)疏松相關(guān)性 骨質(zhì)疏松是由于骨密度降低和骨微結(jié)構(gòu)破壞而導(dǎo)致骨強度降低及骨折風險增加的全身性疾病。骨質(zhì)疏松發(fā)病因素較為復(fù)雜,與肥胖、內(nèi)分泌、遺傳、酗酒等多種因素有關(guān)[6],但具體機制尚未研究清楚。研究表明[7]絕經(jīng)后女性骨質(zhì)疏松發(fā)病率顯著升高。本研究中病例組與對照組一般資料比較差異無統(tǒng)計學意義,排除了一般情況對研究結(jié)果的影響。BGP作為骨基質(zhì)中主要的非膠原蛋白,是骨形成的特異性標志物[8]；BAP作為非單一的同工酶,可反映人體成骨細胞活性,骨質(zhì)疏松患者血清水平顯著降低；BMD是反映骨質(zhì)破壞程度的直接指標[8]；CTX-1作為反映破骨細胞活性及骨吸收的指標,是骨轉(zhuǎn)換標志物中首選的風險評估指標[9],TRACP-5b是反映骨吸收及破骨細胞功能的指標[10]。本研究顯示,病例組BGP、BAP和BMD水平均低于對照組,而CTX-1和TRACP-5b水平均高于對照組,說明病例組患者骨代謝指標發(fā)生了一系列改變,骨形成與骨吸收平衡被打破,從而導(dǎo)致BMD降低,發(fā)生骨質(zhì)疏松。

表1 兩組一般資料比較±s)

表2 兩組血清IGF-1和ET-1水平及骨代謝指標比較

表3 病例組血清IGF-1和ET-1水平與骨代謝指標相關(guān)性

注:*P<0.05

3.2 IGF-1參與骨質(zhì)疏松發(fā)病過程 IGF-1作為骨骼中含量最為豐富的細胞因子,在骨細胞增殖、骨代謝等方能發(fā)揮重要作用,研究表明[11]IGF-1可抑制骨吸收并促進骨形成。同時,IGF-1亦可通過促進血管生成因子(VEGF)在成骨細胞中分泌而促進血管新生,為骨生長提高保障[12]。本研究顯示,病例組IGF-1水平均低于對照組,說明血清IGF-1水平改變與骨質(zhì)疏松發(fā)病有關(guān),Pearson相關(guān)分析顯示病例組血清IGF-1水平與CTX-1和TRACP-5b呈負相關(guān)(P<0.05),而與BGP、BAP和BMD呈正相關(guān)(P<0.05),說明IGF-1參與了骨質(zhì)疏松發(fā)病過程。有研究指出[13],IGF-1參與調(diào)控骨代謝取決于機體內(nèi)雌激素水平。由于絕經(jīng)后老年女性體內(nèi)雌激素水平降低,從而影響和干擾了IGF-1分泌,進而影響骨質(zhì)代謝而促進骨質(zhì)疏松的發(fā)生。

3.3 ET-1參與骨質(zhì)疏松發(fā)病過程 ET-1存在于骨細胞、成骨細胞和破骨細胞,與微循環(huán)血管收縮功能密切相關(guān)[14]。本研究中病例組ET-1水平高于對照組,Pearson相關(guān)分析顯示,病例組血清ET-1水平與BGP、BAP和BMD呈負相關(guān)(P<0.05),而與CTX-1和TRACP-5b呈正相關(guān)(P<0.05),說明ET-1亦參與了骨質(zhì)疏松發(fā)病過程。我們推測,高水平ET-1可對骨組織微循環(huán)產(chǎn)生影響,通過破壞血管內(nèi)皮及改變血流,使血液中的各種微量元素及營養(yǎng)物質(zhì)無法正常進入骨骼組織，導(dǎo)致骨營養(yǎng)代謝障礙,從而加速骨質(zhì)疏松病程。

亦有研究指出[15],IGF-1與ET-1在冠心病患者血漿中呈負相關(guān),參與冠心病發(fā)病過程。本研究亦發(fā)現(xiàn),病例組血清IGF-1水平與ET-1呈負相關(guān),提示IGF-1和ET-1可能相互影響而參與了骨質(zhì)疏松發(fā)病過程,具體機制尚待進一步研究。

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(接收日期：2016-11-15)

Values of changes of serum IGF-1 and ET-1 levels in aged women with osteoporosis

SUNJian,FANGYi-hui,LIUDa

(DeptofBoneTrauma,ChineseMedicineHospitalofLiaochengCity,Liaocheng,Shandong252000,China)

Objective To investigate the values of changes of serum IGF-1 and ET-1 levels in aged women with osteoporosis. Methods Ninty-three cases of aged women with osteoporosis seemed as the case group and 50 cases of healthy older women seemed as the control group were selected. The serum IGF-1 and ET-1 levels and bone metabolism indexes were detected by using ELISA method. The bone mineral density(BMD) of each subject at the L1～4vertebrae and femoral neck were tested by using dual-energy X-ray absorptiometry measuring instrument. The correlations among variables were analyzed by using pearson correlation analysis. Results The serum levels of IGF-1,BGP, BAP and BMD in case group were lower than the control group, and the serum levels of ET-1, CTX-1 and TRACP-5b were higher than the control group, the differences were statistically significant (P<0.001). Pearson correlation analysis showed that serum levels of IGF-1 in case group were negatively correlated with ET-1, CTX-1 and TRACP-5b (P<0.05), while were positively correlated with BGP, BAP and BMD (P<0.05). The serum levels of ET-1 in case group were negatively correlated with BGP, BAP and BMD (P<0.05), while were positively correlated with CTX-1 and TRACP-5b (P<0.05). Conclusions The serum level of IGF-1 in aged women with osteoporosis is reduced, while the serum level of ET-1 is elevated, and they are closely related with BMD and bone metabolism indexes. They might be involved in the pathogenesis of osteoporosis.

aged;women;osteoporosis;insulin-like growth factor-1;endothelin-1

10.3969/j.issn.1008-0287.2017.01.019

遼寧省自然科學基金(編號:2013021054)

1聊城市中醫(yī)醫(yī)院骨創(chuàng)傷科,山東 聊城 2520002中國醫(yī)科大學第四醫(yī)院骨科,遼寧 沈陽 110000

孫 建,男,主治醫(yī)師,主要從事代謝性骨病研究,E-mail:176572191@qq.com

R 681；R 446.112

A

1008-0287(2017)01-0042-04