小剂量纳洛酮联合吗啡对肺癌荷瘤小鼠肿瘤微环境的影响  

Effects of low-dose naloxone combined with morphine on tumor microenvironment in lung cancer tumor-bearing mice

作　　者：赵娜 杜欢 裴晓宁 李明 ZHAO Na;DU Huan;PEI Xiao-ning(Shenzhen Guangming District People's Hospital,Shenzhen 518000,China;不详)

机构地区：[1]深圳市光明区人民医院,广东深圳518000 [2]联勤保障部队第九八〇(白求恩国际和平)医院,石家庄050000

出　　处：《中国处方药》2024年第10期38-42,共5页Journal of China Prescription Drug

基　　金：深圳市光明区软科学研究项目(2021R1019)。

摘　　要：目的观察小剂量纳洛酮联合吗啡对肺癌荷瘤小鼠肿瘤微环境的影响。方法建立肺癌荷瘤小鼠模型,将24只小鼠随机分为4组:模型组(A组)、纳洛酮组(B组)、吗啡组(C组)、纳洛酮联合吗啡组(D组),每组6只,成瘤后在A组颈背部皮下注射生理盐水100μl;B组在颈背部皮下注射纳洛酮0.357 mg/kg;C组在颈背部皮下注射吗啡0.357 mg/kg;D组在颈背部皮下注射纳洛酮0.357 mg/kg+吗啡0.357 mg/kg;每日2次,连续注射14 d。每3天测定1次肿瘤的长径和短径,计算肿瘤的相对体积(RTV);ELISA法检测血清中小鼠肿瘤坏死因子(TNF-α)、小鼠白细胞介素10(IL-10)、小鼠γ干扰素(IFN-γ)、小鼠β-内啡肽(β-EP)、小鼠谷氨酰胺(Gln)的变化情况;免疫组织化学方法检测CD4、CD8、CD158的表达;Western blot法检测肿瘤组织中B细胞淋巴瘤基因-2(Bcl-2)、μ-阿片受体(MOR)、阿片类生长因子受体(OGFR)及程序性死亡蛋白-1受体(PD-1)的表达。结果小剂量纳洛酮联合吗啡组能够抑制RTV;纳洛酮联合吗啡组小鼠血清中IL-10、β-EP水平明显低于模型组;纳洛酮联合吗啡组小鼠荷瘤组织内CD4、CD158蛋白的表达高于模型组,PD-1、MOR、Bcl-2表达明显低于模型组。结论小剂量纳洛酮联合吗啡能够改善肿瘤微环境,其机制可能与其上调CD4、CD158的表达,下调PD-1、MOR、Bcl-2表达有关。Objective To observe the effect of low-dose naloxone combined with morphine on the tumor microenvironment of lung tumorbearing mice.Methods To established a lung tumor-bearing mouse model and randomly divided 24 mice into four groups:model group(group A),naloxone group(group B),morphine group(group C),and naloxone combined with morphine group(Group D),with 6 in each group.After tumor formation,group A was injected with 100μl of normal saline subcutaneously at the back of the neck;group B was injected with naloxone 0.357 mg/kg subcutaneously at the back of the neck;group C was injected with morphine 0.357 mg/kg subcutaneously at the back of the neck;group D was injected naloxone 0.357 mg/kg+morphine 0.357 mg/kg subcutaneously with the back of the neck.2 times a day,continuous injection for 14 days.The long and short diameters of the tumor were measured every three days,calculated the relative volume of the tumor(RTV).The level of mouse tumor necrosis factor(TNF-α),mouse interleukin 10(IL-10),changes in mouse gamma interferon(IFN-γ),mouseβ-endorphin(β-EP),and mouse glutamine(Gln)were detected by ELISA kit.The expressions of CD4,CD8 and CD158 were detected by immunohistochemistry.The expression of Bcl-2,MOR,OGFR,and PD-1 in tumor tissues was detected by the Western blot method.Results Low-dose naloxone combined with morphine group can inhibit RTV;the levels of IL-10 andβ-EP in serum of mice in naloxone combined with morphine group were significantly lower than those in model group.The expression of CD4,CD158 protein in tumor-bearing tissues of mice in naloxone combined with morphine group were higher than that in model group,and the expression of PD-1,MOR、Bcl-2 and was significantly lower than that in model group.Conclusion Lowdose naloxone combined with morphine can improve the tumor microenvironment,and its mechanism may be related to up-regulating the expression of CD4,CD158 and down-regulating the expression of PD-1,MOR,Bcl-2.

关 键 词：吗啡 纳洛酮 肺癌 肿瘤微环境 

分 类 号：R734.2[医药卫生—肿瘤]