年齡對(duì)老年人血清胃蛋白酶原Ⅰ、胃蛋白酶原Ⅱ和胃泌素-17結(jié)果判讀的影響

戎國(guó)棟陳獻(xiàn)吳蕾?gòu)垵嵭耐醴键S珮珺

老年人; 胃蛋白酶原; 胃泌素-17; 年齡; 性別

胃蛋白酶原是由胃黏膜分泌的胃蛋白酶的前體形式,主要包括兩大亞類,胃蛋白酶原Ⅰ(PGⅠ)和胃蛋白酶原Ⅱ(PGⅡ)。PGⅠ主要由胃黏膜的主細(xì)胞和頸黏液細(xì)胞分泌,PGⅡ除了上述細(xì)胞分泌外,還可由胃竇黏液細(xì)胞及近端十二指腸的Brunner腺等合成。血清胃蛋白酶原濃度與其分泌水平相當(dāng),因此其水平的升高或者降低均可直接反映出胃黏膜損傷程度。胃泌素-17(G-17)是由胃竇部G細(xì)胞分泌的一種消化相關(guān)的激素,可促進(jìn)胃酸、胰液和膽汁等的分泌,也可刺激主細(xì)胞分泌胃蛋白酶原。血清G-17水平反映胃竇部的黏膜狀態(tài)。血清PGⅠ、PGⅡ和G-17檢測(cè)均歸為胃功能篩查組套,目前已大規(guī)模應(yīng)用于臨床胃病篩查,被認(rèn)為是胃癌早期診斷和預(yù)后監(jiān)測(cè)的工具。本研究旨在通過(guò)分析體檢人群血清PGⅠ、PGⅡ和G-17水平,探討年齡、性別因素對(duì)上述檢測(cè)結(jié)果的影響。

1 對(duì)象與方法

1.1 研究對(duì)象 收集2016 年1～11月來(lái)我院體檢的居民血清標(biāo)本共計(jì)2732份,并根據(jù)病歷資料排除胃部疾病及十二指腸潰瘍、十二指腸球炎等疾病。年齡10～91歲,其中男1348例,女1384例,根據(jù)PGⅠ、PGⅡ、G-17試劑盒參考范圍分組,3個(gè)指標(biāo)均正常的為正常組,共1016例,其余為異常組,共1716例。按年齡分為非老年亞組(<65歲,2313例)和老年亞組(≥65歲,419例)。

1.2 儀器與試劑 Biohit公司酶聯(lián)免疫吸附法(ELISA)試劑盒測(cè)定血清PGⅠ、PGⅡ和G-17水平。Thermo公司酶標(biāo)儀測(cè)定吸光度值。

1.3 方法 早晨空腹抽取靜脈血,3000 r/min離心5 min,血清置于-4 ℃冰箱保存待用。根據(jù)試劑盒說(shuō)明書(shū)測(cè)定血清PGⅠ、PGⅡ和G-17濃度,計(jì)算PGⅠ/PGⅡ比值(PGR)。根據(jù)試劑盒說(shuō)明書(shū),4個(gè)指標(biāo)的參考值范圍分別是70～165 μg/L、3～15 μg/L、1～15 pmol/L和7～20。

1.4 統(tǒng)計(jì)學(xué)分析 使用SPSS 17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。ln轉(zhuǎn)換用于偏態(tài)分布數(shù)據(jù)向正態(tài)分布轉(zhuǎn)換。2組間定量數(shù)據(jù)比較采用獨(dú)立樣本t檢驗(yàn),并采用相關(guān)分析分析年齡對(duì)4項(xiàng)指標(biāo)的影響。以P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 標(biāo)本分布情況 非老年亞組血清4項(xiàng)指標(biāo)正常率分別為PGⅠ 48.00%,PGⅡ 80.80%,G-17 77.22%和PGR 63.90%;老年亞組正常率分別為PGⅠ 3.10%,PGⅡ 71.12%,G-17 70.64%和PGR 73.51%。

2.2 老年亞組和非老年亞組4項(xiàng)指標(biāo)比較 由于4項(xiàng)指標(biāo)的結(jié)果均呈偏態(tài)分布,因此我們先將所有數(shù)據(jù)進(jìn)行Ln轉(zhuǎn)換再統(tǒng)計(jì)分析。在正常組中,老年亞組血清PGⅠ和PGⅡ水平均高于非老年亞組,而血清G-17水平在老年人中相對(duì)較低,差異均有統(tǒng)計(jì)學(xué)意義;而在異常組,老年人血清G-17反而升高(P<0.01)。正常組老年人血清PGR值與非老年人比較差異無(wú)統(tǒng)計(jì)學(xué)意義;而異常組老年人血清PGR值明顯較非老年人降低,差異具有統(tǒng)計(jì)學(xué)意義(P<0.01),見(jiàn)圖1。

同時(shí)按性別分層分析,結(jié)果發(fā)現(xiàn):(1)正常組中,老年亞組男性血清PGⅠ和PGⅡ水平高于同組女性以及非老年亞組的男性;老年亞組女性G-17水平低于非老年亞組女性;非老年亞組男性PGⅠ水平高于同組女性;(2)異常組中,老年亞組4項(xiàng)指標(biāo)在性別分布中差異均無(wú)統(tǒng)計(jì)學(xué)意義,非老年亞組男性PGⅠ、PGⅡ水平高于女性,G-17水平低于女性;非老年亞組女性PGⅠ、PGⅡ水平低于老年亞組女性,PGR水平高于老年亞組女性;非老年亞組男性PGR水平高于老年亞組男性,而PGⅡ和G-17水平低于老年亞組男性。見(jiàn)圖2。

注:A-D為異常組,E-H為正常組;*P<0.05;**P<0.01圖1 各指標(biāo)分別在異常組和正常組兩個(gè)年齡段的水平比較

注:A-D為異常組,E-H為正常組;*P<0.05;**P<0.01圖2 各指標(biāo)分別在異常組和正常組不同年齡段各性別間的水平比較

2.3 年齡對(duì)血清PGⅠ、PGⅡ,G-17和PGR檢測(cè)結(jié)果的影響 我們使用線性相關(guān)分析探討年齡與這4項(xiàng)指標(biāo)的關(guān)系。結(jié)果顯示,異常組年齡與血清PGⅠ、PGⅡ和G-17水平呈正相關(guān),與PGR呈負(fù)相關(guān)(P<0.05)。而在正常組,年齡與PGⅠ、PGⅡ和G-17均無(wú)統(tǒng)計(jì)學(xué)關(guān)聯(lián)。見(jiàn)圖3。

注:A-0為異常組,E-H為正常組圖3 異常組和正常組各指標(biāo)與年齡因素線性相關(guān)分析

3 討論

已有文獻(xiàn)報(bào)道,≥65歲老年人若PGR值異常,其罹患胃癌的風(fēng)險(xiǎn)大幅增加,是<65歲人群的數(shù)倍[1]。我們的統(tǒng)計(jì)結(jié)果表明,若PGR在正常值范圍內(nèi),年齡越大,此值發(fā)生異常的風(fēng)險(xiǎn)越低;而一旦判定PGR為異常時(shí),老年人相對(duì)于年輕人的結(jié)果更低,說(shuō)明疾病狀態(tài)下老年人PGR降低速度更快。圖1中PGⅠ和PGⅡ的變化趨勢(shì)可以解釋這種現(xiàn)象。正常組老年人PGⅠ水平高于年輕人,而PGⅡ近似,導(dǎo)致PGR與年輕人差異小。而在異常組,老年人PGⅡ升高速度明顯高于年輕人,即PGR迅速下降。PGR下降程度與胃黏膜萎縮情況有關(guān)。在萎縮性胃炎的早期階段,胃蛋白酶原水平均升高,但由于疾病后期主細(xì)胞被幽門(mén)腺細(xì)胞替代,PGⅡ水平持續(xù)上升,導(dǎo)致PGR值下降[2-3]。萎縮性胃炎是胃癌發(fā)生進(jìn)程中的第一階段。老年人較年輕人易罹患萎縮性胃炎及胃癌。因此PGR被認(rèn)為是針對(duì)萎縮性胃炎及胃癌篩查具有高靈敏度和高特異度的關(guān)鍵標(biāo)志[4]。

G-17是定位和評(píng)估胃黏膜萎縮區(qū)域的血清標(biāo)志物。目前,G-17和胃蛋白酶原的聯(lián)合檢測(cè)已經(jīng)成為臨床評(píng)估胃萎縮的重要篩查和監(jiān)測(cè)手段[5]。本研究表明,血清G-17值正常時(shí),老年亞組水平相對(duì)低;而在疾病狀態(tài)下,老年人血清G-17水平反而超過(guò)年輕人。有研究指出,細(xì)胞衰老并不干擾胃部泌酸，相反,大多數(shù)(80%～90%)老年人的胃泌酸功能和年輕人相比并無(wú)明顯差異。Farinat等[6]指出,胃壁細(xì)胞數(shù)量隨著年齡增長(zhǎng)而減少,這會(huì)引起G細(xì)胞代償性分泌G-17以維持其正常水平。本研究還發(fā)現(xiàn),正常組老年男性血清PGⅠ和PGⅡ水平高于同組女性。是否需要建立老年人性別相關(guān)血清PGⅠ和PGⅡ參考區(qū)間以降低檢測(cè)結(jié)果假陽(yáng)性,需要我們收集更多的臨床數(shù)據(jù)來(lái)分析與證實(shí)。

[1] Shafaghi A, Mansour-Ghanaei F, Joukar F, et al. Serum gastrin and the pepsinogen Ⅰ/Ⅱ ratio as markers for diagnosis of premalignant gastric lesions[J]. Asian Pac J Cancer Prev, 2013, 14(6):3931-3936.

[2] Lee JY, Kim N, Lee HS, et al. Correlations among endoscopic, histologic and serologic diagnoses for the assessment of atrophic gastritis[J]. J Cancer Prev, 2014, 19(1):47-55.

[3] Agréus L, Kuipers EJ, Kupcinskas L, et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers[J]. Scand J Gastroenterol, 2012, 47(2):136-147.

[4] Zoalfaghari A, Aletaha N, Roushan N, et al. Accuracy of pepsinogens for early diagnosis of atrophic gastritis and gastric cancer in Iranian population[J]. Med J Islam Repub Iran, 2014, 28:150.

[5] Nejadi-Kelarijani F, Roshandel G, Semnani S, et al. Diagnostic values of serum levels of pepsinogens and gastrin-17 for screening gastritis and gastric cancer in a high risk area in northern Iran[J]. Asian Pac J Cancer Prev, 2014, 15(17):7433-7436.

[6] Farinati F, Formentini S, Della Libera G, et al. Changes in parietal and mucous cell mass in the gastric mucosa of normal subjects with age: a morphometric study[J]. Gerontology, 1993,39(3):146-151.

InfluenceofageoninterpretationofserumpepsinogenⅠ,pepsinogenⅡandgastrin-17inelderly

RONGGuo-dong,CHENXian,WULei,ZHANGJie-xin,WANGFang,HUANGPei-jun.
DepartmentofLaboratoryMedicine,theFirstAffiliatedHospitalofNanjingMedicalUniversity,Nanjing210029,China

ObjectiveTo investigate the impact of age on the levels of serum pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), and gastrin-17 (G-17).MethodsWe collected 2732 serum samples of residents who

health examination in the First Affiliated Hospital of Nanjing Medical University in 2016. Serum levels of PGⅠ, PGⅡ, and G-17 were detected by enzyme linked immunosorbent assay, and then the ratio of PGⅠ to PGⅡ(PGR) was calculated. According to age, gender, and the reference ranges of the detection kits, all data were divided into normal group and abnormal group, elderly sub group and non-elderly sub group. Independent-sample t test, linear correlation analysis were used for statistical analysis.Results(1)In normal group, serum PGⅠ and PGⅡ levels in elderly subgroup were higher than those in non-elderly group, and serum G-17 level was lower than that in non-elderly subgroup. In abnormal group, serum PGⅠ, PGⅡ, and G-17 levels in elderly subgroup were significantly higher than those in non-elderly subgroup, and PGR was significantly lower than that in non-elderly subgroup. (2)In normal group, serum PGⅠ and PGⅡ levels of male in elderly subgroup were higher than those of the female in elderly subgroup and male of non-elderly subgroup； G-17 level of female in elderly subgroup was significantly lower than that in non-elderly subgroup； PGⅠ level of non-elderly subgroup in male was higher than that in female. In normal group, there were no significant difference between different genders in elderly subgroup. Serum PGⅠ and PGⅡ levels of male in non-elderly subgroup were higher than those of female, and G-17 level were significantly lower than that of female; Serum PGⅠ and PGⅡ levels of female in non-elderly subgroup were lower than those of the female in elderly subgroup; PGR level was significantly higher than that of female in elderly subgroup; PGR level of male in non-elderly subgroup was significantly higher, and G-17 level was lower than that of male in elderly subgroup.ConclusionsAge and gender are influencing factors of serum PGⅠ, PGⅡ, and G-17. Both should be concerned in clinical work to decrease false positive rate of the elderly.

aged; pepsinogen; gastrin-17; age; gender

江蘇省自然科學(xué)基金青年基金項(xiàng)目(BK20151029)

210029 江蘇省南京市，南京醫(yī)科大學(xué)第一附屬醫(yī)院檢驗(yàn)學(xué)部

張潔心，Email：jiexinzhang@njmu.edu.cn

目的探討年齡對(duì)血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)和胃泌素-17(G-17)結(jié)果判讀的可能影響。方法收集2016年在南京醫(yī)科大學(xué)第一附屬醫(yī)院進(jìn)行健康體檢的居民血清標(biāo)本共2732份。采用酶聯(lián)免疫吸附法對(duì)血清PGⅠ、PGⅡ和G-17水平進(jìn)行檢測(cè),并計(jì)算PGⅠ和PGⅡ的比值(PGR)。依據(jù)年齡、性別和試劑盒參考值范圍,將所有結(jié)果按照檢測(cè)項(xiàng)目分為正常組(所有指標(biāo)均正常)和異常組(有1項(xiàng)及以上指標(biāo)異常)以及老年亞組和非老年亞組。應(yīng)用ln轉(zhuǎn)換,分別采用獨(dú)立樣本t檢驗(yàn)和線性相關(guān)分析對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)。結(jié)果(1)正常組中,老年亞組血清PGⅠ和PGⅡ水平均高于非老年亞組,血清G-17水平低于非老年亞組。異常組中,老年亞組血清PGⅠ、PGⅡ和G-17水平均高于非老年亞組,而PGR顯著低于非老年亞組,差異有統(tǒng)計(jì)學(xué)意義。(2)進(jìn)一步按性別分層分析,正常組中,老年亞組男性血清PGⅠ和PGⅡ水平高于同組女性以及非老年亞組的男性;老年亞組女性G-17水平低于非老年亞組女性;非老年亞組男性PGⅠ水平高于同組女性。異常組中,老年亞組4項(xiàng)指標(biāo)在性別分布中差異均無(wú)統(tǒng)計(jì)學(xué)意義,非老年亞組男性PGⅠ、PGⅡ水平高于女性,G-17水平低于女性;非老年亞組女性PGⅠ、PGⅡ水平低于老年亞組女性,PGR水平高于老年亞組女性;非老年亞組男性PGR水平高于老年亞組男性,而G-17水平低于老年亞組男性。結(jié)論年齡和性別是影響老年人PGⅠ、PGⅡ和胃泌素-17檢測(cè)結(jié)果的因素。臨床工作中需要考慮這兩個(gè)因素以降低老年人群的假陽(yáng)性率。

R 446.11

A

10.3969/j.issn.1003-9198.2017.11.016

2016-11-22)