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幽门螺杆菌感染作为中央浆液性脉络膜视网膜病变危险因素的研究进展

Research progress on Helicobacter pylori infection as a risk factor for central serous chorioretinopathy

来源期刊: 眼科学报 | 2020年3月 第35卷 第1期 48-52 发布时间: 收稿时间:2022/9/26 15:49:30 阅读量:3885
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幽门螺杆菌中心性浆液性脉络膜视网膜病变危险因素
Helicobacter pylori central serous chorioretinopathy risk factor
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10.3978/j.issn.1000-4432.2019.11.01
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幽门螺杆菌(Helicobacter pylori,H P)感染是中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)的一个危险因素,但是在HP感染和CSC相关性的研究仍存在争议,目前有两种观点:一是认为HP感染可能是CSC的一个危险因素,二是认为两者之间并没有相关性。本文将就对HP感染是否为CSC危险因素文献进行综述,同时探讨其发病机制。
Helicobacter pylori (HP) infection is a risk factor for central serous chorioretinopathy (CSC). But the existing studies tend to support two distinctively different trends regarding the link between HP infection and CSC. The first group tend to support that: HP infection may be a risk of CSC, and the second tend to claim to no correlation between the two. This paper will review the literature on whether HP infection is a risk factor for CSC and discuss its pathogenesis.
中心性浆液性脉络膜视网膜病变(central serous chorioretinopathy,CSC)最早由Von Graefe[1]于1886年描述。发病人群主要为中年人(25~45岁),以男性为主,是一种特发性疾病,其特征是由于黄斑区的视网膜色素上皮(retina pigment epithelium,RPE)屏障功能改变,导致视网膜神经上皮浆液性脱离。许多CSC患者可无症状,可出现视力障碍,如视力下降、视物昏暗、色觉异常、视物变小或变形及中央相对暗区等表现[2]。大多数病例经3~4个月浆液性视网膜神经上皮脱离自发消退愈合。然而,一小部分患者可进展为慢性或复发性,表现为持续6个月以上,可引起的严重视力丧失;这被定义为RPE的弥漫性失代偿[3]。幽门螺杆菌(Helicobacter pylori,HP)是一种革兰氏阴性细菌,与多种消化道和消化道外病变有关。2002年,法国的一个研究小组[4]首次报道了HP与CSC关系,该研究进行前瞻性试验研究,纳入1 6例CSC患者中有9例(56.3%)H P阳性,明显高于一般人群(27.5%)。并在2004年发表了一项补充研究[5],纳入更多病例进一步证实了这一结果。

1 CSC 患者中 HP 感染的患病率

早在2001年,有个案[6]曾报道:在根除胃HP感染时CSC临床症状得到改善,HP感染复发时CSC也复发,因此猜测CSC的发生与HP感染有关。2002年法国的一个研究小组[4]在视觉和眼科研究协会(Association for Research in Vision and Ophthalmology,ARVO)大会的海报上展示了他们的第一个研究结果,即HP感染是CSC的一个危险因素。该研究进行前瞻性试验研究16例CSC患者,发现HP感染的患病率为9/16(56.3%),高于普通人群27.5%;并在2004年发表了一项补充研究[5],该研究纳入更多的CSC患者,发现其HP感染的患病率为31/7(39.7%)高于法国人群的患病率25.4%,进一步证实了这一研究结果。随后许多研究也都支持HP感染是CSC的危险因素[7-12]。Roshani等[12]等在一项涉及35例CSC患者和135例对照组的前瞻性研究中表明:CSR患者的HP感染患病率30/35(85.7%)明显高于对照组76/138(55.1%),研究中使用抗HP标准疗法成功根除HP后,CSR患者的症状有所改善。然而也有研究表明,CSR患者中HP感染的患病率并不比对照组高。Feghhi等[13]在一项病例对照研究中发现:实验组CSC患者中HP感染患病率为37/54(68.5%),与对照组[38/59(65%)]的差异无统计学意义。Warrow等[14]的一项前瞻性研究结果显示:CSC患者18例患者中HP感染的患病率3/18(16.7%)远低于以往以回顾性研究为主的研究(患病率范围:44%~78%)。由于CSC患者中HP感染的患病率仍然存在争议,Bagheri等[15]回顾性研究调查H P感染作为CSC的危险因素进行META分析,该研究共选取9篇论文研究H P感染与CSC的相关性,最终纳入5篇文献进行分析,分析固定效应模型和随机效应模型,结果显示:CSC患者HP感染的患病率分别比对照组高2.5倍和2.7倍,证实CSC患者中HP感染的患病率明显较高,当然他们认为目前仍需要更多的临床试验来明确根除HP对CSC患者预后和治疗的作用。

2 HP 感染引起 CSC 的机制

CSC是一种多灶性脉络膜毛细血管闭塞性疾病,特点是视网膜外屏障破裂,液体通过RPE的缺损渗漏到视网膜下,导致视网膜神经上皮浆液性脱离。但对HP在CSC发病机制仍不确定。对于该发病机制的假说有2种:一是HP感染和动脉粥样硬化之间可能存在联系,HP感染患者抗cagA抗体的交叉反应性和免疫球蛋白G抗体促进血管壁损伤和动脉粥样硬化的发展,内皮细胞功能障碍的机制可以解释HP感染患者CSC的病理生理机制[16];另一个是HP感染会引起热休克蛋白作用[17],针对病原生物抗原的免疫反应会与同源宿主蛋白发生交叉反应,例如与内皮血管壁发生交叉反应,同时内皮细胞黏附分子的上调和多形核白细胞黏附的增加[18],血小板活化和聚集的增加[19],最终导致缺血。Georges等[20]认为:HP感染与血管内皮疾病(如特发性中浆、冠状动脉疾病)的相互作用是由血清IL-6水平的变化介导的,也可能参与CSC的病理生理过程。另外,通过激光多普勒血流仪、荧光素和吲哚菁绿眼底血管造影以及共聚焦扫描激光检眼镜显示了凹脉络膜血流减少。这些非灌注区可能是脉络膜动脉和绒毛膜毛细血管充盈延迟所导致的[21]。以上脉络膜微循环引改变引起的局灶性闭塞以及HP与血管内皮的相互作用,可以解释HP感染患者脉络膜缺血的机制和CSC的发生发展。

3 结语

综上所述,大部分研究认为H P感染可能是CSC的一个危险因素,其病理机制可能与动脉粥样硬化及血管内皮损伤有关。当然目前仍需要更多的临床试验来明确根除HP对CSC患者预后和治疗的作用。如果这一关系得到证实,一种新的CSC治疗方案将被引入。希望今后能通过动物实验和病理检验解释HP引CSC发病机制。由于各种族的体质有差异,同时国内对此项临床研究鲜有报道,因此也期待国内对探讨HP感染与CSC的相关性进行大样本多中心临床研究的开展。

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1、薛愚愚,周琦,宿晓娟等.幽门螺杆菌与眼部疾病相关性研究进展[J].国际眼科杂志,2023,23(07):1158-1162.XUE Yuyu, ZHOU Qi, SU Xiaojuan, et al. Research progress on the correlation between Helicobacter pylori and ocular diseases[J]. Int Eye Sci, 2023, 23(7): 1158-1162.
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