大鼠胰腺癌模型及其化学趋化因子mRNA表达与肿瘤相关巨噬细胞计数的关系

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目的研究SD鼠胰腺导管癌和非癌胰腺组织白细胞介素(IL)8、单核细胞趋化蛋白(MCP)1和巨噬细胞炎性蛋白(MIP)1αmRNA表达及其与肿瘤相关巨噬细胞(TAM)计数的关系。方法将二甲基苯并蒽(DMBA)置入大鼠胰腺实质内及设立曲古霉素(TSA)干预组(B组),3~5个月内处死观察胰腺癌发生情况;行3种mRNA原位杂交及TAM免疫组织化学染色。结果A组肿块直径明显大于B组(P<0.05),A组和B组纤维肉瘤均发生胰腺外转移。(2)A组和B组胰腺导管癌3种mRNA表达阳性率及其评分均明显高于非癌组织(B组中MCP1mRNA除外)(P<0.01),C组均呈阴性表达;且A组明显高于B组(P<0.05)。(3)A组和B组胰腺导管癌TAM计数明显高于非癌组织和C组(P<0.01);3~4个月A组和B组TAM计数低于5个月组(P<0.01)。(4)IL8mRNA阳性胰腺癌TAM数明显高于阴性者(P<0.01),其评分值与TAM计数之间呈正相关(r=0.32,P<0.05)。结论DMBA置入胰实质内可在短期获得较高的SD鼠胰腺癌发生率,TSA能抑制胰腺癌发生和生长,其作用可能与抑制化学趋化因子表达和TAM浸润有关;3种化学趋化因子和TAM可能与胰腺癌发生发展有较密切关系。 Objective To study the expression of interleukin (IL) 8, monocyte chemoattractant protein (MCP) 1 and macrophage inflammatory protein (MIP) 1αmRNA in pancreatic ductal carcinoma and non-cancerous pancreatic tissues of SD rats and their relationship with tumor-associated macrophages (TAM) count relationship. Methods DMBA was placed in the parenchyma of pancreas and TSA intervention group (group B). The rats were sacrificed within 3 to 5 months to observe the occurrence of pancreatic cancer. mRNA in situ hybridization and TAM immunohistochemical staining. Results The diameter of tumor mass in group A was significantly larger than that in group B (P <0.05). The metastases of pancreas in group A and group B occurred. (2) The positive expression rates and the scores of three kinds of mRNA of pancreatic ductal carcinomas in group A and group B were significantly higher than those in non-cancerous tissues (except for MCP1 mRNA in group B) (P <0.01), and negative in group C Was significantly higher than the B group (P <0.05). (3) TAM counts of pancreatic ductal carcinoma in group A and group B were significantly higher than those in non-cancerous tissue and group C (P <0.01); TAM in group A and B were lower than that in group C ). (4) The positive rate of TAM in IL8mRNA positive pancreatic carcinoma was significantly higher than that in negative ones (P <0.01). There was a positive correlation between the score and TAM count (r = 0.32, P <0.05). CONCLUSIONS: The placement of DMBA in the parenchyma of the pancreas can achieve a higher incidence of pancreatic cancer in SD rats in short term. TSA can inhibit the occurrence and growth of pancreatic cancer, which may be related to the inhibition of chemotactic factor expression and TAM infiltration. Three chemotactic chemotaxis Factors and TAM may be more closely related to the development of pancreatic cancer.
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