年齡對老年人血清胃蛋白酶原Ⅰ、胃蛋白酶原Ⅱ和胃泌素-17結果判讀的影響

年齡對老年人血清胃蛋白酶原Ⅰ、胃蛋白酶原Ⅱ和胃泌素-17結果判讀的影響

戎國棟陳獻吳蕾張潔心王芳黃珮珺

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胞和頸黏液細胞分泌,PGⅡ除了上述細胞分泌外,還可由胃竇黏液細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,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細胞分泌的一種消化相關的激素,可促進胃酸、胰液和膽汁等的分泌,也可刺激主細胞分泌胃蛋白酶原。血清G-17水平反映胃竇部的黏膜狀態。血清PGⅠ、PGⅡ和G-17檢測均歸為胃功能篩查組套,目前已大規模應用于臨床胃病篩查,被認為是胃癌早期診斷和預后監測的工具。本研究旨在通過分析體檢人群血清PGⅠ、PGⅡ和G-17水平,探討年齡、性別因素對上述檢測結果的影響。

1 對象與方法

1.1 研究對象 收集2016 年1～11月來我院體檢的居民血清標本共計2732份,并根據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PGⅠ、PGⅡ、G-17試劑盒參考范圍分組,3個指標均正常的為正常組,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公司酶聯免疫吸附法(ELISA)試劑盒測定血清PGⅠ、PGⅡ和G-17水平。Thermo公司酶標儀測定吸光度值。

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。根據試劑盒說明書測定血清PGⅠ、PGⅡ和G-17濃度,計算PGⅠ/PGⅡ比值(PGR)。根據試劑盒說明書,4個指標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 統計學分析 使用SPSS 17.0軟件進行統計學分析。ln轉換用于偏態分布數據向正態分布轉換。2組間定量數據比較采用獨立樣本t檢驗,并采用相關分析分析年齡對4項指標的影響。以P<0.05為差異具有統計學意義。

2 結果

2.1 標本分布情況 非老年亞組血清4項指標正常率分別為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項指標比較 由于4項指標的結果均呈偏態分布,因此我們先將所有數據進行Ln轉換再統計分析。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較低,差異均有統計學意義;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統計學意義;而異常組老年人血清PGR值明顯較非老年人降低,差異具有統計學意義(P<0.01),見圖1。

同時按性別分層分析,結果發現:(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項指標在性別分布中差異均無統計學意義,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 各指標分別在異常組和正常組兩個年齡段的水平比較

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 年齡對血清PGⅠ、PGⅡ,G-17和PGR檢測結果的影響 我們使用線性相關分析探討年齡與這4項指標的關系。結果顯示,異常組年齡與血清PGⅠ、PGⅡ和G-17水平呈正相關,與PGR呈負相關(P<0.05)。而在正常組,年齡與PGⅠ、PGⅡ和G-17均無統計學關聯。見圖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與年齡因素線性相關分析

3 討論

已有文獻報道,≥65歲老年人若PGR值異常,其罹患胃癌的風險大幅增加,是<65歲人群的數倍[1]。我們的統計結果表明,若PGR在正常值范圍內,年齡越大,此值發生異常的風險越低;而一旦判定PGR為異常時,老年人相對于年輕人的結果更低,說明疾病狀態下老年人PGR降低速度更快。圖1中PGⅠ和PGⅡ的變化趨勢可以解釋這種現象。正常組老年人PGⅠ水平高于年輕人,而PGⅡ近似,導致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。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胞被幽門腺細胞替代,PGⅡ水平持續上升,導致PGR值下降[2-3]。萎縮性胃炎是胃癌發生進程中的第一階段。老年人較年輕人易罹患萎縮性胃炎及胃癌。因此PGR被認為是針對萎縮性胃炎及胃癌篩查具有高靈敏度和高特異度的關鍵標志[4]。

G-17是定位和評估胃黏膜萎縮區域的血清標志物。目前,G-17和胃蛋白酶原的聯合檢測已經成為臨床評估胃萎縮的重要篩查和監測手段[5]。本研究表明,血清G-17值正常時,老年亞組水平相對低;而在疾病狀態下,老年人血清G-17水平反而超過年輕人。有研究指出,細胞衰老并不干擾胃部泌酸，相反,大多數(80%～90%)老年人的胃泌酸功能和年輕人相比并無明顯差異。Farinat等[6]指出,胃壁細胞數量隨著年齡增長而減少,這會引起G細胞代償性分泌G-17以維持其正常水平。本研究還發現,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血清PGⅠ和PGⅡ參考區間以降低檢測結果假陽性,需要我們收集更多的臨床數據來分析與證實。

[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.

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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

江蘇省自然科學基金青年基金項目(BK20151029)

210029 江蘇省南京市，南京醫科大學第一附屬醫院檢驗學部

張潔心，Email：jiexinzhang@njmu.edu.cn

目的探討年齡對血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)和胃泌素-17(G-17)結果判讀的可能影響。方法收集2016年在南京醫科大學第一附屬醫院進行健康體檢的居民血清標本共2732份。采用酶聯免疫吸附法對血清PGⅠ、PGⅡ和G-17水平進行檢測,并計算PGⅠ和PGⅡ的比值(PGR)。依據年齡、性別和試劑盒參考值范圍,將所有結果按照檢測項目分為正常組(所有指標均正常)和異常組(有1項及以上指標異常)以及老年亞組和非老年亞組。應用ln轉換,分別采用獨立樣本t檢驗和線性相關分析對數據進行統計。結果(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,差異有統計學意義。(2)進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項指標在性別分布中差異均無統計學意義,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。結論年齡和性別是影響老年人PGⅠ、PGⅡ和胃泌素-17檢測結果的因素。臨床工作中需要考慮這兩個因素以降低老年人群的假陽性率。

R 446.11

A

10.3969/j.issn.1003-9198.2017.11.016

2016-11-22)