質(zhì)子泵抑制劑和結(jié)腸息肉相關(guān)性研究

顧怡雯, 華　靜, 陳勝良, 江偉駿

(1. 上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院 消化科, 上海, 200025;2. 上海交通大學(xué)醫(yī)學(xué)院附屬同仁醫(yī)院 消化科, 上海, 200336)

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質(zhì)子泵抑制劑和結(jié)腸息肉相關(guān)性研究

顧怡雯1, 華靜1, 陳勝良1, 江偉駿2

(1. 上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院 消化科, 上海, 200025;2. 上海交通大學(xué)醫(yī)學(xué)院附屬同仁醫(yī)院 消化科, 上海, 200336)

目的探討質(zhì)子泵抑制劑(PPIs)和結(jié)腸息肉形成兩者間的關(guān)系。方法將本院結(jié)腸息肉的患者設(shè)為病例組(154例)，腸炎及未見異常者設(shè)為對(duì)照組(98例)。調(diào)查所有入組人員飲食及生活習(xí)慣、PPIs服用等情況，并測定血胃泌素水平。各因素先進(jìn)行單因素分析，有統(tǒng)計(jì)學(xué)意義者進(jìn)一步行多因素Logistic回歸。結(jié)果 單因素分析提示PPIs與結(jié)腸息肉的發(fā)生及生長部位有關(guān)(P<0.05), 結(jié)腸息肉組中服用PPIs的患者與未服用PPIs患者的胃泌素水平有顯著差異[(115±19.4) ng/L vs (66.4±8.4) ng/L],P<0.001), 但病例組與對(duì)照組兩者間胃泌素水平無明顯差異(P=0.191,P>0.05), 且進(jìn)一步多因素Logistic分析提示PPIs變量無統(tǒng)計(jì)學(xué)意義(P=0.081,P>0.05)。結(jié)論本研究無法證實(shí)與結(jié)腸息肉形成是否存在必然相關(guān)性, PPIs與結(jié)腸息肉之間是否存在關(guān)聯(lián)尚待進(jìn)一步研究。

質(zhì)子泵抑制劑; 胃泌素; 結(jié)腸息肉: Logistic模型；

有研究[1]表明長期服用質(zhì)子泵抑制劑(PPIs)的患者胃泌素水平明顯增高，而胃泌素對(duì)腸上皮有促生長作用。有實(shí)驗(yàn)[2]發(fā)現(xiàn)高胃泌素血癥可增加APC基因突變大鼠結(jié)直腸息肉的發(fā)生率。因此，長期服用PPIs可能是形成結(jié)腸息肉的危險(xiǎn)因素。本文探討PPIs與結(jié)腸息肉形成的關(guān)系，現(xiàn)報(bào)告如下。

1　資料與方法

1.1一般資料

選取2013年6—12月在上海交通大學(xué)附屬同仁醫(yī)院行結(jié)腸鏡檢查發(fā)現(xiàn)結(jié)腸息肉的患者設(shè)為結(jié)腸息肉組，以上病例均經(jīng)病理證實(shí)，腸炎及未見異常者設(shè)為對(duì)照組。服用PPIs常規(guī)劑量1年以上或1年內(nèi)間斷服藥時(shí)間累計(jì)超過6個(gè)月以上為PPIs服用組。

1.2研究方法

以問卷調(diào)查的方式了解所有入組人員有無PPIs服用史、服用原因及使用時(shí)間，對(duì)個(gè)人家族史、飲食及生活習(xí)慣進(jìn)行調(diào)查。行結(jié)腸鏡檢查前抽血測定胃泌素水平。

1.3統(tǒng)計(jì)學(xué)分析

應(yīng)用SSPS 19.0統(tǒng)計(jì)軟件，先以卡方檢驗(yàn)對(duì)可能與腸息肉形成有關(guān)的變量行單因素分析(α=0.05), 其中均值比較采用t檢驗(yàn)，采用多因素條件Logistic回歸分析法分析有統(tǒng)計(jì)學(xué)意義的變量,P<0.05為差異有統(tǒng)計(jì)學(xué)差異。

2　結(jié)　果

結(jié)腸息肉組納入共154例，男81例，女73例，年齡40～88歲，平均(69.3±9.5)歲；對(duì)照組共98例，男32例，女66例，年齡38～84歲，平均(65.5±10.7)歲。單因素分析顯示，2組在性別、年齡、息肉家族史、體質(zhì)量指數(shù)、PPIs服用史方面均有顯著差異(P<0.05)。見表1。結(jié)腸息肉組中服用PPIs患者的胃泌素水平明顯高于未服用者(P<0.01)。進(jìn)一步對(duì)息肉的部位、數(shù)量及病理類型進(jìn)行統(tǒng)計(jì)分析，發(fā)現(xiàn)服用PPIs對(duì)息肉生長部位有顯著影響(P<0.05)，服用PPIs患者發(fā)生遠(yuǎn)端結(jié)腸息肉的比例較高(81.8%)，但患者的息肉大小、數(shù)量、病理類型與服用PPIs均無明顯相關(guān)。見表2。進(jìn)一步行多因素Logistic回歸分析見表3。

3　討　論

從結(jié)腸黏膜的表面突出延伸至腸腔的尚未明確病理性質(zhì)的息肉狀病變?yōu)榻Y(jié)腸息肉，從病理的角度可以將其分為腫瘤性息肉和非腫瘤性息肉，前者為腺瘤，后者包括錯(cuò)構(gòu)瘤性息肉、炎性及增生性息肉、淋巴性息肉等[3]。在所有的息肉中，腺瘤占70～80%[4]。結(jié)直腸腺瘤主要是由結(jié)直腸癌衍變而來，對(duì)結(jié)腸息肉的發(fā)病原因以及相關(guān)危險(xiǎn)因子的研究可以幫助篩查、預(yù)防結(jié)腸癌，使癌癥致死率下降[5]。

多項(xiàng)研究[6]表明，長期使用PPIs可引發(fā)高胃泌素血癥。其機(jī)制為PPIs與壁細(xì)胞H+-K+-ATP酶不可逆的結(jié)合，從而阻斷胃酸分泌，從而使胃內(nèi)的pH值增高，促使胃泌素從G細(xì)胞內(nèi)大量釋放，最終形成高胃泌素血癥[7]。據(jù)研究[8]報(bào)道，使用PPIs后，血清胃泌素可增高3～5倍，而使用H2受體阻滯劑，胃泌素增高不明顯，一般低于2倍。

胃泌素是胃腸道G細(xì)胞所分泌的一種多肽激素，在動(dòng)物和腫瘤細(xì)胞研究[9]發(fā)現(xiàn)，胃泌素可以促進(jìn)胃酸分泌，還可以通過自分泌、旁分泌和神經(jīng)內(nèi)分泌等方式對(duì)結(jié)腸黏膜有營養(yǎng)作用，并促進(jìn)胃腸黏膜上皮細(xì)胞的增生，以利于腫瘤細(xì)胞的快速增殖。因胃腸息肉的形成與腺上皮細(xì)胞增生密切相關(guān)，從而增加腸息肉形成的風(fēng)險(xiǎn)，有學(xué)者[10]證實(shí)高胃泌素血癥增加APC基因突變大鼠結(jié)直腸息肉的發(fā)生率，但臨床中尚未證實(shí)高胃泌素水平與腸息肉有確切關(guān)系。長時(shí)間服用PPls藥物的患者中，只有10～30%被發(fā)現(xiàn)存在結(jié)節(jié)性、線性或者彌漫性增生的腸細(xì)胞，尤其是胃泌素濃度顯著上升、幽門螺旋桿菌(HP)呈陽性以及中度或重度萎縮性胃炎的患者[11]。有研究[12]認(rèn)為在上述現(xiàn)象中起主導(dǎo)作用的是HP感染和HP誘導(dǎo)的環(huán)氧合酶-2(COX-2)表達(dá)，一旦COX-2的表達(dá)水平過高，其能多步驟及多方面地使腫瘤的整個(gè)發(fā)生發(fā)展過程加快，而并非單純胃泌素的增高導(dǎo)致腸息肉的發(fā)生。

表1　單因素分析篩選結(jié)腸息肉相關(guān)因素[n(%)]

表2 　結(jié)腸息肉組PPIs服用和腸息肉 臨床特征的關(guān)系[n(%)]

表3　結(jié)腸息肉的危險(xiǎn)因素Logistic回歸分析

本研究中，單因素分析提示服用PPIs與結(jié)腸息肉的發(fā)生及生長部位有關(guān)(P<0.05), 同時(shí)研究顯示結(jié)腸息肉組中服用PPIs的患者胃泌素水平顯著高于未服用PPIs者，服用PPIs可導(dǎo)致胃泌素水平增高。進(jìn)一步多因素Logistic分析提示, PPIs變量無統(tǒng)計(jì)學(xué)意義(P>0.05), 無法證實(shí)與結(jié)腸息肉形成是否存在必然相關(guān)性。Logistic回歸分析結(jié)果提示患者的年齡、性別、BMI、息肉家族史均為結(jié)腸息肉形成的獨(dú)立危險(xiǎn)因素[13]。

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Correlation between proton pump inhibitors and the growth of colonic polyps

GU Yiwen1, HUA Jing1, CHEN Shengliang1, JIANG Weijun2

(DepartmentofGastroenterology,RenjiHospitalAffiliatedtoSchoolofMedicineofShanghaiJiaotongUniversity,Shanghai, 200025;DepartmentofGastroenterology,TongrenHospitalAffiliatedtoSchoolofMedicineofShanghaiJiaotongUniversity,Shanghai, 200336)

ObjectiveTo study the relationship of proton pump inhibitors and the growth of colonic polyps. MethodsA total of 154 patients who underwent colonoscopy in our hospital were as patients group and 98 healthy cases were as controls. Dietary and life style factors and family history of two groups were investigated. And serum gastrin levels were examined in all patients. Suspected variables were screened by univariate analysis and those with statistical significant were further analyzed by multivariate conditional Logistic regression. ResultsPPIs was found to be correlated with the growth of colonic polyps and growth distribution (P<0.05). In patients with colonic polyps, the mean gastrin level in PPI users versus non-PPI users was (115±19.4) ng/L versus (66.4±8.4) ng/L, respectively (P<0.001), but there was no difference in serum gastrin levels in two groups(P=0.191,P>0.05). Further multivariate conditional Logistic regression analysis demonstrated that there was no significant difference in variable PPIs. ConclusionThe research cannot confirm that PPIs is related to the growth of colonic polyps, and it remains further exploration.

proton pump inhibitors; gastrin; colonic polyps; Logistic models

2016-05-12

R 574.62

A

1672-2353(2016)17-050-03

10.7619/jcmp.201617016