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目的探讨多分子靶点药物索拉菲尼(Sorafenib)对肝细胞癌(hepatocellular carcinoma,HCC)形成过程中巨噬细胞标记物CD68和自然杀伤细胞标记物CD57的分布、表达情况的影响。方法改良法建立HCC模型,设立正常对照组(A组)、单纯模型组(B组)、早期单倍组(C组)、早期双倍组(D组)、晚期单倍组(E组)、晚期双倍组(F组),在HCC形成早期和晚期应用单、双倍剂量的索拉菲尼对C～F组进行干预,用免疫组织化学方法动态观察HCC组织中CD57、CD68和CD34的变化。结果B组CD57、CD68阳性细胞的数目逐渐增加,各个实验组(C～F组)分别在第12、14周时出现峰值后不同程度的减少,而D、F组在第18周后两者数目减少不明显,其中第20、22周时D、F组分别与B组相比均显著增加(P<0.05),同时D组比C组,F组比E组以及D组比F组亦显著增加(P<0.01,P<0.05),其余各组之间比较差异无统计学意义(P>0.05)。B组CD34阳性细胞数目逐渐增加,各个实验组(B～F组)在第16周后随诱癌时间延长有不同程度的减少,D组与C、E、F组相比亦显著减少(P<0.05)。结论索拉菲尼不仅可以抑制HCC组织的血管生成,还可以诱导HCC组织中的巨噬细胞和自然杀伤细胞的聚集,以早期双倍剂量组更明显,提示索拉菲尼治疗HCC的分子机制可能存在一种新的免疫调节机制,并呈剂量依赖性。
Objective To investigate the effect of multidrug target drug Sorafenib on the distribution and expression of macrophage marker CD68 and natural killer marker CD57 in hepatocellular carcinoma (HCC). The HCC model was established by the improved method. The normal control group (group A), the simple model group (group B), the early haploid group (group C), the early double group (group D) and the late haploid group (group E) (Group F). Single and double doses of sorafenib were administered to C ~ F group in early and late stage of HCC formation. The expression of CD57, CD68 and CD34 in HCC tissues were observed by immunohistochemical method The change. Results The number of CD57 and CD68 positive cells in group B increased gradually. The peak value of each group was observed at 12 and 14 weeks in each experimental group (C ~ F group) (P <0.05). At the same time, D group was more than C group, F group was more than E group and D group was more than F group (P <0.01, P <0.05). There was no significant difference between the other groups (P> 0.05). The number of CD34 positive cells in group B gradually increased. The number of CD34 positive cells in each group (B ~ F group) decreased with the prolongation of the duration of cancer after 16 weeks, but also decreased in group D compared with those in groups C, E and F (P <0.05). Conclusion Sorafenib can not only inhibit the angiogenesis of HCC tissues, but also induce the aggregation of macrophages and natural killer cells in HCC tissues, which is more obvious in the early double-dose group and suggests the molecular mechanism of sorafenib in the treatment of HCC There may be a new immunomodulatory mechanism in a dose-dependent manner.