产毒幽门螺杆菌可引起大鼠胃黏膜微循环的改变。
Toxigenic Helicobacter pylori induces changes in the gastric mucosal microcirculation in rats.
作者信息
Kalia N, Bardhan K D, Atherton J C, Brown N J
机构信息
Section of Surgical and Anaesthetic Sciences, Division of Clinical Sciences (S), Royal Hallamshire Hospital, Sheffield, UK.
出版信息
Gut. 2002 Nov;51(5):641-7. doi: 10.1136/gut.51.5.641.
BACKGROUND AND AIMS
One of the key components of inflammation is changes in vascular structure and function. This suggests that the microcirculation may be a key target of Helicobacter pylori released factors. It has previously been shown in vivo that pooled H pylori extracts from duodenal ulcer/gastritis patients induce platelet aggregation but no leucocyte activation within rat gastric mucosal microcirculation (GMMC). However, infection with strains associated with ulcer disease as compared with gastritis may exert greater effects on the microcirculation. This study used fluorescent in vivo microscopy to determine the acute effects of extracts of genotypically different H pylori strains on the GMMC.
METHODS
Three H pylori extracts, with different cagA and VacA toxigenic status, were individually administered to the gastric mucosa of anaesthetised Wistar rats. The mucosal surface was visualised via an incision made in the exteriorised stomach. Fluoroscein isothiocyanate conjugated to bovine serum albumin (FITC-BSA) or acridine orange was used to quantify macromolecular leak (MML) and leucocyte/platelet activity respectively for 120 minutes. Changes in capillary and post-capillary venule (PCV) diameters were also monitored.
RESULTS
The cagA(+) VacA toxigenic strain 60190 induced significant and sustained MML by five minutes (p<0.01). Transient and less leakage was observed with its isogenic VacA(-) mutant and other non-toxigenic strains regardless of cagA status. Significant increases in leucocyte adhesion (p<0.05), platelet aggregation (p<0.05), and PCV vasoconstriction (p<0.05) were only observed with the cag A(+) and toxigenic strain.
CONCLUSION
Extracts of H pylori are capable of inducing marked disturbances within the rat GMMC. These disturbances seem to be dependent on the production of an active vacuolating cytotoxin. Varying effects on the GMMC may explain the clinically diverse outcomes associated with genotypically different strains.
背景与目的
炎症的关键组成部分之一是血管结构和功能的改变。这表明微循环可能是幽门螺杆菌释放因子的关键作用靶点。此前在体内研究中发现，十二指肠溃疡/胃炎患者的幽门螺杆菌混合提取物可诱导大鼠胃黏膜微循环（GMMC）中的血小板聚集，但不会引起白细胞激活。然而，与胃炎相关菌株相比，溃疡病相关菌株的感染可能对微循环产生更大影响。本研究采用体内荧光显微镜来确定基因分型不同的幽门螺杆菌菌株提取物对GMMC的急性影响。
方法
将三种具有不同cagA和VacA产毒状态的幽门螺杆菌提取物分别施用于麻醉的Wistar大鼠的胃黏膜。通过在胃外置手术切口观察黏膜表面。异硫氰酸荧光素结合牛血清白蛋白（FITC-BSA）或吖啶橙分别用于在120分钟内定量大分子渗漏（MML）和白细胞/血小板活性。同时监测毛细血管和毛细血管后微静脉（PCV）直径的变化。
结果
cagA(+) VacA产毒株60190在5分钟时即可诱导显著且持续的MML（p<0.01）。无论cagA状态如何，其同基因VacA(-)突变体和其他非产毒株均观察到短暂且较少的渗漏。仅在cag A(+)产毒株中观察到白细胞黏附（p<0.05）、血小板聚集（p<0.05）和PCV血管收缩（p<0.05）显著增加。
结论
幽门螺杆菌提取物能够在大鼠GMMC内诱导明显的紊乱。这些紊乱似乎依赖于活性空泡细胞毒素的产生。对GMMC的不同影响可能解释了与基因分型不同菌株相关的临床多样结局。
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