| Objectives: Macrophage polarization is closely related to tumor growth and metastasis of colon cancer.Opioids can induce macrophages to polarize to a certain phenotype,and then affect the function of macrophages.Sufentanil is the most commonly used opioid for perioperative anesthesia and analgesia in tumor patients.In this study,a fixed interval dose of sufentanil was used to simulate perioperative analgesia,observe the effect of sufentanil on macrophage polarization and colon cancer metastasis,and explore the possible mechanism of sufentanil induced macrophage polarization affecting colon cancer tumor growth and metastasis.Methods: The mouse model of blood metastasis of colon cancer was established by injecting CT26 colon cancer cells into tail vein.The mice were divided into three groups: blank control group(NS group),low dose sufentanil group(LSF group)and high dose sufentanil group(HSF group).Each group was administered at 2 hours before injection of CT26 cells(T1),1 hour before injection of CT26 cells(T2),1 hour after injection of CT26 cells cells(T3),2 hours after injection of CT26 cells(T4),the first day after injection of CT26 cells(T5)and the second day after injection of CT26cells(T6).Normal saline(NS),low-dose sufentanil(LSF,0.02mg/kg)and high-dose sufentanil(HSF,0.06mg/kg)were injected intraperitoneally respectively,and the materials were taken on the 14 th and 21 st days after tumor inoculation.(1)The venous blood of mice was collected and the serum was prepared.M1 polarization-related factor TNF-α and i NOS,and M2 polarization-related factors Arg1 and CD206 were detected by ELISA.The ratio of i NOS and Arg1 in each group was compared to judge the polarization direction of macrophages.(2)The metastasis of colon cancer cells in each group was observed,and the specimens of lung tissue and extrapulmonary tumor tissue were collected and stained with HE to observe the metastasis of tumor cells in lung tissue and extrapulmonary tissue.Results:1.On the 14 th day after injection of tumor cells,compared with NS group,there was no significant difference in serum TNF-α concentration in LSF group(P>0.05),but the serum TNF-α concentration in HSF group increased significantly(P<0.05).On the 21 st day after injection of tumor cells,compared with NS group,there was no significant difference in serum TNF-α concentration in LSF group(P>0.05),but the serum TNF-αconcentration in HSF group decreased significantly(P<0.05).Compared with the 14 th day,on the 21 st day after injection of tumor cells,the serum TNF-α concentration in NS group increased significantly(P<0.05),and decreased significantly in HSF group(P<0.05),but there was no difference in serum TNF-α concentration in LSF group(P>0.05).2.On the 14 th day after injection of tumor cells,compared with NS group,the expression level of serum i NOS in LSF group and HSF group decreased significantly(P<0.05),and the expression level of serum i NOS in HSF group decreased more significantly(P<0.001).On the 21 st day after tumor cell injection,compared with NS group,the expression level of i NOS in LSF group and HSF group decreased significantly(P<0.05).Compared with the 14 th day,on the 21 st day after tumor cell injection,the expression level of i NOS in HSF group increased significantly(P<0.05),but there was no difference between NS group and LSF group(P>0.05).3.On the 14 th day after injection of tumor cells,compared with NS group,the expression level of serum Arg1 in LSF group had no significant difference(P>0.05),while the concentration of serum Arg1 in HSF group decreased significantly(P<0.05).Compared with LSF and HSF,the expression level of serum Arg1 in HSF group was significantly lower than that in LSF group(P<0.05).On the 21 st day after injection of tumor cells,compared with NS group,the expression level of serum Arg1 in LSF group decreased significantly(P<0.05),but there was no difference in the expression level of serum Arg1 in HSF group(P>0.05).Compared with the14 th day,on the 21 st day after injection of tumor cells,there was no significant difference in the expression level of Arg1 in serum of mice in each group(P>0.05).4.On the 14 th day after injection of tumor cells,compared with NS group,the expression level of serum CD206 in LSF group increased significantly(P<0.05),while that in high-dose sufentanil group(HSF)decreased significantly(P<0.05).Compared with LSF and HSF,the expression level of serum CD206 in HSF group was significantly lower than that in LSF group(P<0.05).On the 21 st day after injection of tumor cells,there was no significant difference in the expression level of serum CD206 in each group of mice(P>0.05).Compared with the 14 th day,on the 21 st day after tumor cell injection,the expression level of serum CD206 in NS group and LSF group decreased significantly(P<0.05),but there was no difference in the expression of serum CD206 in HSF group(P>0.05).5.On the 14 th day after injection of tumor cells,the i NOS/Arg1 ratio in HSF group was significantly higher than that in NS group(P<0.01)and LSF group(P<0.01),but there was no significant difference in i NOS/Arg1 ratio between LSF group and NS group(P>0.05).On the 21 st day after injection of tumor cells,the i NOS/Arg1 ratio in LSF group was significantly higher than that in NS group(P<0.05)and HSF group(P<0.05).There was no significant difference in i NOS/Arg1 ratio between HSF group and NS group(P>0.05).6.In the saline group,CT26 colon cancer cells were transferred to lung,abdominal liver,mesentery,and peritoneum.After sufentanil administration,CT26 colon cancer cells were almost not colonized in abdominal cavity,but tended to colonize in lung.Both low-dose and highdose sufentanil can inhibit the metastasis and colonization of CT26 colon cancer cells into abdominal cavity.Conclusions:1.Sufentanil can reduce the metastasis and colonization of CT26 colon cancer cells to the distant abdominal cavity.2.Sufentanil inhibited the expression of marker cytokines of M1 or M2 macrophages in mice.Sufentanil can make macrophages tend to polarize towards M1. |
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