胃泌素和生长抑素对人十二指肠粘膜表皮生长因子含量的影响

1、    胃泌素和生长抑素对人十二指肠粘膜 表皮生长因子含量的影响        摘要目的和方法：通过体外孵育试验，研究胃泌素和生长抑素对十二指肠和十二指肠溃疡(Du)旁粘膜表皮生长因子(EGF)含量的影响。结果：活动期Du旁粘膜EGF含量减少，愈合期含量增高。五肽胃泌素可显著增加粘膜EGF含量；生长抑素类似物奥曲肽可减少愈合期Du旁粘膜EGF含量，并有抑制五肽胃泌素增加EGF含量的作用。结论：十二指肠粘膜EGF含量减少可能是Du的发病因素之一；胃泌素可刺激十二指肠粘

2、膜EGF合成，而生长抑素可抑制胃泌素的作用。主题词表皮生长因子尿抑胃素；胃泌素类；生长抑素；十二指肠溃疡 Effects of gastrin and somatostatin on epidermal growth factor contents in human duodenal mucosa in vitroZHAO Kui，MA Shu-Yu，HE Yong-Heng,SONG Jian，LONG XiaoYing,GAO Yuan,LIU Mu-RongDepartment of Gastroenterology,Affiliated Hospital,Zunyi Medical C

3、ollege,Zunyi(563003)AbstractAIM and METHODS：Effects of gastrin and somatostatin on duodenal mucosal epidermal growth factor (EGF)contents were studied in normal subjects and patients with duodenal ulcer(Du).After duodenal biopsies were cultured in vitro for 24 h under various experimental conditions

4、,EGF contents in homogenized biopsy specimens were determined by radioimmunoassy.RESULTS：EGF contents in mucosa around ulcer were decreased in active Du and increased in healing Du.EGF contents were increased significantly in normal and Du mucosa,when pentagastrin(100 g/L and 200 g/L)was added,and d

5、ecreased markedly in healing Du mucosa after somatostatin analogue octreotide (10 g/L and 20 g/L)was added to the media.Addition of pentagastrin(200 g/L)and octreotide(20 g/L)together to the media,EGF contents were not changed in the mucosa of normal and Du.CONCLUSION：The fall of EGF contents in duo

6、denal mucosa may be involved in the pathogenesis of Du.Gastrin can stimulate the production of EGF from duodenal mucosa and somatostatin can inhibite EGF production stimulated by gastrin in the mucosa.MeSHEpidermal growth factor-urogastrone; Gastrins; Somatostatin; Duodenal ulcer表皮生长因子(epidermal gro

7、wth factor,EGF)是一种含53个氨基酸的多肽因子，具有抑制胃酸分泌、粘膜保护和促进溃疡愈合等多种作用1。上消化道EGF产生的主要部位是唾液腺和十二指肠Brunner腺2。有关EGF在十二指肠溃疡(duonenal ulcer,Du)发病中的作用及胃肠激素对EGF分泌的调节尚不十分清楚。本研究通过体外实验进一步探讨胃泌素和生长抑素对正常十二指肠和Du旁粘膜EGF含量的影响。材料与方法一、研究对象：正常对照组10例，男6例，女4例，年龄2056岁，平均(41.0±10.3)岁；活动期Du组16例，男10例，女6例，年龄2258岁，平均(43.5±14.1)岁；愈合期

8、Du组12例，男7例，女5例，年龄1861岁，平均(44.4±14.8)岁。所有对象均为随机收集经胃镜检查和粘膜活检组织学检查确诊者。无其他系统慢性疾病。检查前1周内未服用制酸剂、H2结果活动期Du旁粘膜EGF含量分别显著低于正常十二指肠(P0.05)和愈合期Du旁粘膜(P0.01)，愈合期Du旁粘膜EGF含量高于正常十二指肠(P0.05)。五肽胃泌素可显著增加正常十二指肠和活动期及愈合期Du旁粘膜EGF含量，五肽胃泌素100g/L可分别使正常十二指肠、活动期和愈合期Du旁粘膜EGF含量增高146%±64%、214%±101%和170%±43%，三组比较

9、增高的百分比幅度差异无显著意义；五肽胃泌素200g/L使活动期和愈合期Du旁粘膜EGF增高300%±108%和249%±39%，显著高于正常十二指肠粘膜195%±66%的增高幅度(P均0.05)。奥曲肽10和20g/L可显著降低愈合期Du旁粘膜EGF含量(P分别0.05和0.01)，正常十二指肠和活动期Du旁粘膜EGF含量也有所减少，但与空白对照比较差异无显著。奥曲肽(20g/L)具有显著抑制五肽胃泌素(200g/L)增加正常十二指肠及Du旁粘膜EGF含量的作用(表1)。表1五肽胃泌素和奥曲肽对正常十二指肠和Du旁粘膜EGF含量的影响TreatmentDose(g

10、/L)Mucosal EGF(ng/mg pro)Normal(n10）ADu(n16）HDu(n12）Vehicle*Pentagastrin 100200Octreotide1020Pentagastrinoctreotide20020     Normal：normal duodenal mucosa;ADu：adjacent mucosa of active duodenal ulcer;HDu:adjacent mucosa of healing duodenal ulcer;Vehicle:added PBS to the media as

11、vehicle.P0.05，vs normal group;P0.01，vs ADu group;P0.05，P0.01，vs vehicle in same group;P0.05，P0.01，vs pentagastrin 100g/L in same group 讨论EGF具有很强的促进DNA合成、上皮细胞再生和胃肠道粘膜保护作用，另外可通过刺激前列腺素合成、协同生长抑素抑制胃酸、促进胃液分泌而增强对胃肠粘膜的保护效应1。有研究显示，消化性溃疡患者唾液和胃液EGF含量减少3。Zandomeneghi等发现活动期Du边缘组织EGF含量显著低于正常十二指肠粘膜4。本文亦证实活动期Du旁粘膜E

12、GF含量显著降低，提示十二指肠Brunner腺破坏或分泌EGF减少可能在Du的发病中起一定作用。本研究发现愈合期Du旁粘膜EGF含量显著高于正常十二指肠和活动期Du旁粘膜。Wright等通过免疫组织化学染色观察到，消化道溃疡形成后溃疡旁粘膜干细胞可形成大量新的分泌EGF细胞5。愈合期Du旁粘膜EGF含量增高可能与大量再生粘膜细胞产生EGF增多有关，这可能是粘膜损伤后的一种自身修复机制。EGF合成与分泌的调节机制尚不清楚。已发现咀嚼可促使唾液EGF分泌，胃泌素可使唾液和十二指肠分泌物EGF含量增高6；血管活性肠肽和胰泌素可刺激十二指肠粘膜分泌EGF4，7，而生长抑素可抑制胰泌素促EGF分泌7。本

13、研究显示，在体外五肽胃泌素可显著增加正常十二指肠和Du旁粘膜EGF含量，其中对Du旁粘膜EGF增高的百分比幅度大于正常十二指肠粘膜，提示Du旁粘膜细胞对胃泌素的反应性增高。胃泌素除可刺激壁细胞分泌胃酸外，同时具有促使胃、十二指肠粘膜细胞增殖、分化的作用，胃泌素的胃肠粘膜营养作用部分与激活酪氨酸蛋白激酶有关，而EGF的受体正是具有酪氨酸激酶活性的跨膜蛋白，因此推测胃泌素使粘膜EGF合成增加可能是其胃肠粘膜的营养作用机理之一。生长抑素具有抑制胃酸分泌、消化道吸收及运动等多种生理功能，还可抑制几乎所有胃肠激素的释放。Du旁粘膜生长抑素含量减少4。奥曲肽为人工合成的八肽生长抑素类似物，其作用强度及半衰

14、期均大于天然生长抑素。本研究发现，奥曲肽可显著减少愈合期Du旁粘膜EGF含量，并能抑制五肽胃泌素刺激十二指肠粘膜EGF的增加，提示生长抑素可能有拮抗胃泌素促粘膜EGF合成的作用。胃泌素和生长抑素对EGF合成的相互调控，可能是维持损伤组织修复和细胞增殖的机制之一。作者单位：遵义医学院附属医院消化内科(遵义563003)参考文献1Konturek SJ.Role of growth factor in gastroduodenal protection and healing of peptic ulcers.Gastroenterol Clin North Am,1990,19(1):41.2E

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16、t al.The role of epidermal growth factor in the pathogenesis of peptic ulcer disease.Am J Gastroenterol,1991,86(9)：1150.5Wright NA,Pike CM,Elia G,et al.Induction of a novel epidermal growth factorsecreting cell lineage by mucosal ulceration in human gastrointestinal stem cell.Nature,1990,343(6253):82.6Konturek JW,Bielanski W,Konturek SJ,et al.Distribution and release of epiderm