摘要
目的探讨HMGB1/TLR2/NF-κB在溃疡性结肠炎(UC)小鼠结肠组织中的表达及作用机制。方法 BALB/C小鼠随机分为正常对照组及模型组,每组12只;正常对照组不造模,模型组用恶唑酮(OXZ)灌肠复制UC模型。观察两组实验小鼠体质量变化、大体及组织病理学改变;RT-PCR检测结肠组织HMGBlmRNA的表达变化;免疫组织化学和流式细胞术检测结肠组织中HMGB1、TLR2、NF-κB蛋白的表达变化。结果与正常对照组小鼠相比,模型组小鼠出现不同程度的腹泻和便血,结肠黏膜明显充血、水肿,可见较大溃疡病灶;模型组小鼠结肠组织中HMGB1mRNA及蛋白表达升高,主要位于细胞浆和细胞外;模型组小鼠结肠组织TLR2和NF-κB蛋白表达亦明显升高;HMGB1蛋白与TLR2蛋白表达呈显著正相关(r=0.81,P<0.01);TLR2蛋白与NF-κB蛋白表达呈显著正相关(r=0.78,P<0.01)。结论 HMGB1在小鼠溃疡性结肠炎中的致炎作用可能部分通过结合其受体TLR2,激活NF-κB信号途径而实现的。
Objective To quantify expression of HMGBl/TLR2/NF-ΚB in ulcerative colitis and to investigate its role involving pathological mechanisms. Methods BALB/c mice were randomly divided into normal control group and model group（n=12）. The UC model was induced by oxazolone（OXZ）. Rats were observed body weight changes,gross and histopathological changes. HMGBl mRNA expression was detected by RT-PCR;The expression of HMGB1,NF-κB and TLR2 protein was detected by immunohistochemical staining and FCM. Results Compared with normal control mice,the UC mice with varying degrees of diarrhea and blood in the stool,colonic mucosal hyperemia,edema,showing a larger ulcer lesions;Model mice colon tissue HMGB1 mRNA and protein expression increased,mainly located in cytoplasm and extracellular;UC mice colonic tissue TLR2 and NF-κB protein expression also increased significantly;HMGB1 protein expression and TLR2 was significantly positive correlated（r=0.81,P0.01）;TLR2 protein and NF-κB protein expression was significantly correlated （r=0.78,P0.01）. Conclusions HMGB1 induced inflammation in ulcerative colitis in mice,may be partly through its receptor combining TLR2 and activation of NF-κB signaling.
出处
《中华保健医学杂志》
2010年第6期452-455,共4页
Chinese Journal of Health Care and Medicine
基金
上海交通大学创新课题基金资助(091024855)
