To evaluate the therapeutic effect of CXCL1 monoclonal antibody on dextra sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice, and to elucidate its effect on the expressions of TNF-α, IFN-γ, IL-17 and IL-10 as well as neutrophil infiltration. Methods: Female BALB/c mice were randomly divided into a normal group (DSS-), a disease group (DSS+saline), an anti-CXCL1 antibody group (DSS+anti-CXCL1 Ab) and a treatment control group (DSS+IgG Ab). The DSS+saline, DSS+anti-CXCL1 Ab and DSS+anti-CXCL1 Ab groups were given 3.5% DSS solution as drinking water to induce acute intestinal inflammation, while the normal control was given distilled water freely. The DSS+anti-CXCL1 Ab mice were intraperitoneal injected with anti-CXCL1 Ab (4 mg/kg) on the 3rd and 6th day. Same amount of rat IgG Ab was given in the DSS+IgG Ab group. The normal group and the disease group were injected with 0.9% sodium chloride solution. The value of disease activity index (DAI) and the injury of colorectal tissue were measured. The levels of TNF-α, IFN-γ, IL-10 and IL-17 in colonic tissues of mice were detected by RT-PCR. Myeloperoxidase (MPO), a specific marker of neutrophils was measured by immunohistochemistry. Results: Compared with the normal control group, DAI score and colorectal injury score in the disease group were significantly increased, but the DAI and colorectal in the mice with acute ulcerative colitis tissue damage score were significantly reduced after anti-CXCL1 Ab intervention. Compared with the normal control group, mRNA levels of TNF-α, IFN-γ and IL-17 in the colorectal tissues were significantly elevated (P<0.05) in the disease group while the IL-10 was decreased; these effects were attenuated by anti-CXCL1 Ab intervention (P<0.05). Immunohistochemistry showed that the infiltration of neutrophils (MPO+) in the colon tissue was significantly increased in the disease group, while the anti-CXCL1 Ab treatment could significantly reduce the neutrophil infiltration in colon tissue (P<0.05). Conclusion: Anti-CXCL1 Ab relieves the progression of DSS-induced acute ulcerative colitis by suppressing proinflammatory expression and neutrophil infiltration.
目的：探讨抗CXC趋化因子配体1(CXCL1)中和抗体对葡聚糖硫酸钠(dextra sulfate sodium，DSS)诱导的急性溃疡性结肠炎(ulcerative colitis，UC)小鼠模型的治疗作用，并阐明其对结肠组织中细胞因子TNF-α，IFN-γ，IL-17，IL-10的表达及中性粒细胞浸润的影响。方法：雌性BALB/c小鼠48只，随机分为正常对照组(DSS-)、疾病组(DSS+saline)、抗CXCL1中和抗体治疗组(DSS+anti-CXCL1 Ab)和治疗对照组(DSS+IgG Ab)，每组12只。正常对照组小鼠给予蒸馏水自由饮用，疾病组、治疗组及治疗对照组给予3.5%的DSS自由饮用，至第8天处理小鼠。其中治疗组于造模第3天和第6天腹腔注射抗CXCL1中和抗体(4 mg/kg)，治疗对照组予以等量大鼠IgG抗体，正常对照组和疾病组注射等量生理盐水。对各组小鼠进行疾病活动指数评分(disease activity index，DAI)及结直肠组织损伤学评分，并采用RT-PCR法检测各组小鼠结肠组织中细胞因子TNF-α，IFN-γ，IL-17和IL-10的表达。运用免疫组织化学检测各组小鼠结肠组织中中性粒细胞特异性标志物髓过氧化物酶(myeloperoxidase，MPO)的表达。结果：与正常对照组相比，疾病组小鼠DAI评分及结直肠组织损伤学评分明显增高，但是予以抗CXCL1中和抗体干预治疗后能明显减低急性UC小鼠的DAI和结直肠组织损伤学评分。RT-PCR检测结果显示：与正常对照组相比，疾病组小鼠结直肠组织中促炎细胞因子TNF-α，IFN-γ和IL-17 mRNA表达水平均显著升高，抑炎因子IL-10 mRNA表达下降。而使用抗CXCL1中和抗体干预治疗，明显抑制DSS诱导的小鼠结肠组织中促炎细胞因子TNF-α，IFN-γ和IL-17 mRNA表达水平的升高及抑炎因子IL-10 mRNA表达水平的下降，差异具有统计学意义(P<0.05)。免疫组织化学结果显示：疾病组小鼠结肠组织中中性粒细胞的浸润明显增加，予以抗CXCL1中和抗体治疗能显著减少结肠组织中中性粒细胞的浸润，差异具有统计学意义(P<0.05)。结论：抗CXCL1中和抗体缓解了DSS诱导的急性UC的进展，其发挥抗炎作用的机制可能与抑制促炎因子的表达和中性粒细胞的浸润有关。.