表皮生长因子受体抗体抑制胆管炎的效果

Effects of epidermal growth factor receptor antibody on cholangitis

目的探讨胆管应用表皮生长因子受体单克隆抗体Cetuximab对慢性增生性胆管炎(CPC)的抑制作用。方法 SD大鼠46只,随机分为CPC模型组(10只)、Cetuximab治疗组(30只)和假手术组(SO,6只)3组。CPC模型组及Cetuximab治疗组胆总管留置尼龙线复制胆管炎模型。Cetuximab治疗组分为3个亚组,造模的同时分别给予0.05%、0.10%、0.20%的Cetuximab。SO组仅开关腹。1周后取标本。通过HE、Masson、PAS染色、免疫组织化学及RT-PCR评估Cetuxiamb对CPC的抑制效果、浓度效果关系及机制。结果 Cetuximab治疗组胆管炎症增生程度轻于CPC模型组。Cetuximab治疗组各亚组比较:Cetuximab 0.10%组(C 0.10%组)与Cetuximab 0.20%组(C 0.20%组)差异不明显,抑制作用强于Cetuximab 0.05%组(C 0.05%组)。免疫组织化学及RT-PCR提示Cetuximab治疗组EGFR和EGFR的mRNA表达弱于CPC模型组(P<0.05),C 0.10%组及C0.20%组差异无统计学意义,两组均弱于C 0.05%组(P<0.05)。结论 Cetuximab能有效抑制CPC,作用效果有受体饱和效应,对防治肝内胆管结石有较好的应用前景。

【Objective】 To investigate the inhibitory action of epidermal growth factor receptor monoclonal antibody cetuximab on cell proliferation in chronic proliferative cholangitis（CPC）.【Methods】 46 SD rats were assigned to 3 groups randomly.They were CPC group（n =10）,cetuximab therapeutic group（n =30） and shame operation group（n =6） respectively.Rat model in CPC and cetuximab group was established by introducing a nylon stylolite into common bile duct.In cetuximab therapeutic group,cetuximab was administered into the common bile duct with concentration of 0.05%,0.1% and 0.2% respectively.As regards to shame operation group,surgical incision and suture of the abdomen were made as controls.Bile duct was removed 7 days after the initial operation.The anti-proliferation effect,dose-response relationship,and potential mechanism of cetuximab in chronic proliferative cholangitis was assessed through HE,PAS,Masson,immunohisto chemistry and RT-PCR of EGFR.【Results】 The degree of proliferation in cetuximab therapeutic group was less than that of CPC model group.No difference was found between 0.1% cetuximab subgroup（C 0.1%） and 0.2% Cetuximab subgroup（C 0.2%）,however,the degree of proliferation of those two groups was less than that of 0.05% cetuximab subgroup（C 0.05%）.The levels of EGFR and the expression of EGFR mRNA in C 0.2% and C 0.1% subgroup were less than that of CPC model group and no differences of the expression of EGFR and EGFR mRNA were found between C 0.1% and C 0.2% subgroup,nevertheless those expressions of above two subgroups were lower than that of C 0.05% subgroup.【Conclusions】 Cetuximab can effectively suppress proliferation in chronic proliferative cholangitis（CPC）,and it may provide practical value in the treatment of intrahepatic chalangiocarcinoma.