Maity Pallab, Biswas Kaushik, Roy Somenath, Banerjee Ranajit K, Bandyopadhyay Uday
Department of Physiology, Indian Institute of Chemical Biology, Kolkata, India.
Mol Cell Biochem. 2003 Nov;253(1-2):329-38. doi: 10.1023/a:1026040723669.
Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H2-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.
消化性溃疡是消化系统的一种常见疾病，其发病机制是多因素的，吸烟和尼古丁具有显著的不良影响。吸烟和长期尼古丁治疗会刺激基础胃酸分泌，这在患有十二指肠溃疡的吸烟者中更为明显。这种胃酸分泌增加是通过肥大细胞脱颗粒后释放的组胺刺激H2受体介导的，并且是由于吸烟者功能性壁细胞体积或分泌能力的增加。吸烟和尼古丁还通过增加主细胞数量或增强其分泌能力来刺激胃蛋白酶原分泌。对大鼠进行长期尼古丁治疗也会显著减少黏液颈细胞总数和颈细胞黏液量。吸烟还会增加胆汁盐反流率和胃胆汁盐浓度，从而增加十二指肠-胃反流，提高吸烟者患胃溃疡的风险。吸烟和尼古丁不仅会诱发溃疡，还会增强由幽门螺杆菌、酒精、非甾体抗炎药或冷束缚应激引起的溃疡。多形核中性粒细胞（PMN）通过增加活性氧中间体（ROI）的生成对黏膜进行氧化损伤，在溃疡形成过程中起重要作用，而尼古丁和吸烟会增强这种损伤。尼古丁通过环磷酸腺苷-蛋白激酶A信号系统提高内源性血管加压素水平，这在胃十二指肠病变的发展中起促发作用。吸烟会增加血小板活化因子（PAF）和内皮素的产生，它们是强效的胃溃疡原。吸烟和尼古丁会降低循环表皮生长因子（EGF）的水平，并减少唾液腺中EGF的分泌，而EGF是胃黏膜细胞更新所必需的。尼古丁还会减少吸烟者胃黏膜中前列腺素的生成，从而使黏膜易患溃疡。ROI的生成以及ROI介导的胃黏膜细胞凋亡也被认为是香烟烟雾或尼古丁加重溃疡的重要机制。吸烟和尼古丁都会通过抑制一氧化氮合成来减少胃黏膜中的血管生成，从而阻碍细胞更新过程。吸烟或烟雾提取物会损害溃疡的自发愈合和药物诱导的愈合。烟雾提取物还会通过降低鸟氨酸脱羧酶的活性来抑制胃黏膜细胞增殖，鸟氨酸脱羧酶可合成促进生长的多胺。结论是，胃黏膜完整性是由一些控制凋亡细胞死亡和细胞增殖的侵袭性和防御性因素相互作用来维持的，而吸烟通过扰乱这种平衡来加重溃疡。
