作者：晏根贵，颜国富等
来源：掌上医讯
幽门螺杆菌（HP）感染可能是世界范围内最常见的慢性细菌感染之一。胃是幽门螺杆菌感染的主要部位，包括慢性活动性胃炎、消化性溃疡、胃腺癌和B型低度黏膜相关淋巴组织淋巴瘤。 H. Pylori是致胃局部炎症及某些能导致胃肠外的全身性炎症，如心血管疾病、特发性血小板较少性紫癜，不明原因缺铁性贫血、糖尿病（DM）与胰岛素抵抗的罪魁祸首。不同的研究报告了慢性幽门螺杆菌感染的流行与胃肠道和肠外疾病有关。 幽门螺杆菌引起的胃肠道炎症也影响糖尿病患者糖和脂肪的吸收。糖尿病已被确定为幽门螺杆菌感染的胃外表现的一个危险因素。 幽门螺杆菌与糖尿病的关系在1989年由西蒙等人进行了首次探讨。他们发现，糖尿病患者幽门螺杆菌感染率明显高于无症状对照组（62对21%）。 幽门螺旋杆菌感染与糖尿病之间的联系仍然存在争议，因为一些研究表明糖尿病患者感染率较高，而另一些研究报告没有差异。最近的证据表明炎症参与了2型糖尿病（T2DM）的病理变化，这是幽门螺杆菌感染引起的一个重要过程。由于胰岛素抵抗可以在炎症状态下发生，也可能是由于影响胰岛素的反调节激素的改变而产生的。因此，Aydemir等研究者报道幽门螺杆菌可能通过诱导慢性炎症及影响胰岛素调节胃肠激素来促进胰岛素抵抗。此外，幽门螺杆菌感染与2型糖尿病的发病密切相关，这与自身免疫系统的普遍激活有关，与慢性炎症因子介导的低度炎症状态有关。宿主对幽门螺杆菌感染的免疫反应是复杂的，包括上调一些促炎性细胞因子，如C-反应蛋白（CRP）、白细胞介素6（IL-6）和肿瘤坏死因子-α（TNF-α），它们与胰岛素抵抗和糖尿病的发展有关。因此，高度怀疑幽门螺杆菌感染与糖尿病之间的潜在关系。因氧自由基过度产生及内源性或外源性的创伤导致的氧化应激会损害大分子细胞，导致DNA损伤，蛋白质修饰，脂质过氧化，并伴随着心血管、慢性炎症和癌症等多种疾病的发展。据报道 ROS的产生在DM和幽门螺旋杆菌感染中增加，这可能通过几种机制直接导致氧化应激的产生。
幽门螺杆菌感染诱导中性粒细胞和巨噬细胞浸润和活化。据报道，幽门螺杆菌感染患者中性粒细胞浸润及DNA氧化损伤均增强。此外，幽门螺杆菌介导的胃粘膜炎症部位中性粒细胞积聚和氧化应激诱导胃黏膜炎性病变时ox-LDL表达的增强，幽门螺杆菌阳性慢性胃炎患者血浆ox-LDL水平升高。另一方面，氧化应激可以诱导经葡萄糖氧化而导致的高血糖状态及糖基化终产物的形成（AGE）。其他在糖尿病患者中升高的循环因子，如游离脂肪酸和瘦素，也有助于增加活性氧的产生。此外，氧化应激与胰岛功能恶化密切相关。
已观察到糖尿病患者中ox-LDL增加， 这可能有助于解释在糖尿病患者中动脉粥样硬化增加的原因，无论正常的血脂水平，糖尿病患者的LDL水平可能升高，这可能是内皮功能改变的原因。内皮细胞暴露于低密度脂蛋白（LDL）可引起内皮细胞损伤等改变。ox-LDL激活炎性细胞，增强自身从单核/巨噬细胞生长因子的释放。
ROS很容易攻击DNA中的鸟嘌呤，并形成8-hydroxydeoxy鸟苷活性氧鸟嘌呤碱基（8-OHdG），该碱基可以结合胸腺嘧啶而不是胞嘧啶，基于此，8-OHdG的水平通常被视为一种生物标志物的诱变引起氧化应激，并为许多疾病包括幽门螺杆菌感染与糖尿病的危险因素。 最近的一项研究报告显示与对照组相比I型糖尿病 （胰岛素依赖型）和 II型糖尿病 （非胰岛素依赖型）患者中的单核细胞的ROS水平和8-OHdG含量增加。另一项研究报道，幽门螺旋杆菌引起的慢性炎症反应和氧化应激，创造一个有利于DNA损伤和组织损伤的环境。
先前报道的研究是基于研究氧化应激在幽门螺杆菌和糖尿病中的作用。然而，据我们所知，糖尿病和氧化状态之间的联系在幽门螺旋杆菌感染以前没有被研究过。 然而，最近有一项研究观察到2型糖尿病似乎与幽门螺杆菌感染的氧化应激增加有关。并首次报道了氧化DNA损伤、血清ox-LDL水平与幽门螺杆菌感染阳性2型糖尿病患者的直接关联。发现幽门螺杆菌感染阳性的T2DM患者中血清ox-LDL水平显著升高，提示幽门螺杆菌阳性的2型糖尿病患者血清高ox-LDL水平被认为是动脉粥样硬化性血管疾病的危险因素。
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