作者：晏根貴，顏國富等
來源：掌上醫(yī)訊
幽門螺桿菌（HP）感染可能是世界范圍內最常見的慢性細菌感染之一。胃是幽門螺桿菌感染的主要部位，包括慢性活動性胃炎、消化性潰瘍、胃腺癌和B型低度黏膜相關淋巴組織淋巴瘤。 H. Pylori是致胃局部炎癥及某些能導致胃腸外的全身性炎癥，如心血管疾病、特發(fā)性血小板較少性紫癜，不明原因缺鐵性貧血、糖尿?。―M）與胰島素抵抗的罪魁禍首。不同的研究報告了慢性幽門螺桿菌感染的流行與胃腸道和腸外疾病有關。 幽門螺桿菌引起的胃腸道炎癥也影響糖尿病患者糖和脂肪的吸收。糖尿病已被確定為幽門螺桿菌感染的胃外表現(xiàn)的一個危險因素。 幽門螺桿菌與糖尿病的關系在1989年由西蒙等人進行了首次探討。他們發(fā)現(xiàn)，糖尿病患者幽門螺桿菌感染率明顯高于無癥狀對照組（62對21%）。 幽門螺旋桿菌感染與糖尿病之間的聯(lián)系仍然存在爭議，因為一些研究表明糖尿病患者感染率較高，而另一些研究報告沒有差異。最近的證據(jù)表明炎癥參與了2型糖尿?。═2DM）的病理變化，這是幽門螺桿菌感染引起的一個重要過程。由于胰島素抵抗可以在炎癥狀態(tài)下發(fā)生，也可能是由于影響胰島素的反調節(jié)激素的改變而產(chǎn)生的。因此，Aydemir等研究者報道幽門螺桿菌可能通過誘導慢性炎癥及影響胰島素調節(jié)胃腸激素來促進胰島素抵抗。此外，幽門螺桿菌感染與2型糖尿病的發(fā)病密切相關，這與自身免疫系統(tǒng)的普遍激活有關，與慢性炎癥因子介導的低度炎癥狀態(tài)有關。宿主對幽門螺桿菌感染的免疫反應是復雜的，包括上調一些促炎性細胞因子，如C-反應蛋白（CRP）、白細胞介素6（IL-6）和腫瘤壞死因子-α（TNF-α），它們與胰島素抵抗和糖尿病的發(fā)展有關。因此，高度懷疑幽門螺桿菌感染與糖尿病之間的潛在關系。因氧自由基過度產(chǎn)生及內源性或外源性的創(chuàng)傷導致的氧化應激會損害大分子細胞，導致DNA損傷，蛋白質修飾，脂質過氧化，并伴隨著心血管、慢性炎癥和癌癥等多種疾病的發(fā)展。據(jù)報道 ROS的產(chǎn)生在DM和幽門螺旋桿菌感染中增加，這可能通過幾種機制直接導致氧化應激的產(chǎn)生。
幽門螺桿菌感染誘導中性粒細胞和巨噬細胞浸潤和活化。據(jù)報道，幽門螺桿菌感染患者中性粒細胞浸潤及DNA氧化損傷均增強。此外，幽門螺桿菌介導的胃粘膜炎癥部位中性粒細胞積聚和氧化應激誘導胃黏膜炎性病變時ox-LDL表達的增強，幽門螺桿菌陽性慢性胃炎患者血漿ox-LDL水平升高。另一方面，氧化應激可以誘導經(jīng)葡萄糖氧化而導致的高血糖狀態(tài)及糖基化終產(chǎn)物的形成（AGE）。其他在糖尿病患者中升高的循環(huán)因子，如游離脂肪酸和瘦素，也有助于增加活性氧的產(chǎn)生。此外，氧化應激與胰島功能惡化密切相關。
已觀察到糖尿病患者中ox-LDL增加， 這可能有助于解釋在糖尿病患者中動脈粥樣硬化增加的原因，無論正常的血脂水平，糖尿病患者的LDL水平可能升高，這可能是內皮功能改變的原因。內皮細胞暴露于低密度脂蛋白（LDL）可引起內皮細胞損傷等改變。ox-LDL激活炎性細胞，增強自身從單核/巨噬細胞生長因子的釋放。
ROS很容易攻擊DNA中的鳥嘌呤，并形成8-hydroxydeoxy鳥苷活性氧鳥嘌呤堿基（8-OHdG），該堿基可以結合胸腺嘧啶而不是胞嘧啶，基于此，8-OHdG的水平通常被視為一種生物標志物的誘變引起氧化應激，并為許多疾病包括幽門螺桿菌感染與糖尿病的危險因素。 最近的一項研究報告顯示與對照組相比I型糖尿病 （胰島素依賴型）和 II型糖尿病 （非胰島素依賴型）患者中的單核細胞的ROS水平和8-OHdG含量增加。另一項研究報道，幽門螺旋桿菌引起的慢性炎癥反應和氧化應激，創(chuàng)造一個有利于DNA損傷和組織損傷的環(huán)境。
先前報道的研究是基于研究氧化應激在幽門螺桿菌和糖尿病中的作用。然而，據(jù)我們所知，糖尿病和氧化狀態(tài)之間的聯(lián)系在幽門螺旋桿菌感染以前沒有被研究過。 然而，最近有一項研究觀察到2型糖尿病似乎與幽門螺桿菌感染的氧化應激增加有關。并首次報道了氧化DNA損傷、血清ox-LDL水平與幽門螺桿菌感染陽性2型糖尿病患者的直接關聯(lián)。發(fā)現(xiàn)幽門螺桿菌感染陽性的T2DM患者中血清ox-LDL水平顯著升高，提示幽門螺桿菌陽性的2型糖尿病患者血清高ox-LDL水平被認為是動脈粥樣硬化性血管疾病的危險因素。
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