Hahm K B, Lee K J, Kim Y S, Kim J H, Cho S W, Yim H, Joo H J
Department of Gastroenterology and Anatomic Pathology, Ajou University School of Medicine, Suwon, Korea.
Dig Dis Sci. 1998 Sep;43(9 Suppl):192S-197S.
The aim of the present study was to determine the efficacy of a new combination regimen including antioxidant, proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastritis. From each of 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection, five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for experimental measures. The patients were then treated either with lansoprozole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks. Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured. Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) -mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates. Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially in the LAM-treated group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of the antioxidative drug rebamipide to the eradication regimen against H. pylori has quantitative and qualitative advantages such as either augmenting the eradication rates of H. pylori or decreasing oxidative stress and cytokines levels generated by H. pylori infection.
本研究的目的是确定一种新的联合治疗方案（包括抗氧化剂、质子泵抑制剂和抗生素）对幽门螺杆菌的疗效，并记录幽门螺杆菌相关性胃炎中氧化应激和细胞因子的变化。从57例经内镜诊断为与幽门螺杆菌感染相关的胃和/或十二指肠溃疡的患者中，各取5份胃窦活检标本用于幽门螺杆菌诊断和实验检测。然后，患者分别接受兰索拉唑30mg+阿莫西林1.5g（LA组；21例患者）或兰索拉唑30mg+阿莫西林1.5g+瑞巴派特300mg（LAM组；36例患者）治疗两周。治疗开始四周后，再次对患者进行内镜检查并获取活检标本。检测黏膜丙二醛（MDA）水平、髓过氧化物酶（MPO）活性、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、细胞因子IL-1、IL-6、TNF-α以及趋化因子IL-8、GRO-α、调节激活正常T细胞表达和分泌因子（RANTES）。使用石蜡包埋组织切片，进行原位末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）检测细胞凋亡，并进行诱导型一氧化氮合酶（iNOS）免疫组化染色。LA方案治疗两周导致幽门螺杆菌根除率为57.4%，而LAM方案治疗两周导致根除率为75.0%。这两组之间的根除率在统计学上有显著差异（P<0.05）。LAM组的黏膜MDA水平和MPO活性显著低于LA组。幽门螺杆菌治疗后，细胞因子IL-1、IL-6和TNF-α以及趋化因子IL-8、GRO-α和RANTES的黏膜水平均显著降低，尤其是在LAM治疗组。根除幽门螺杆菌后，凋亡指数和iNOS评分显著降低。在根除幽门螺杆菌的治疗方案中添加抗氧化药物瑞巴派特有定量和定性优势，如提高幽门螺杆菌根除率或降低幽门螺杆菌感染产生的氧化应激和细胞因子水平。
