摘要
目的:通过探讨云芝糖肽(PSP)在荷瘤小鼠体内的免疫调节及信号转导机制,研究PSP对荷瘤小鼠My D88信号转导通路的调控作用,验证My D88依赖途径是PSP免疫调节抗肿瘤的重要信号通路。方法:用C57BL/6小鼠建立艾氏腹水癌(EAC)实体型荷瘤小鼠模型,分为2组:野生型(WT)组与基因缺陷型(My D88-/-)组,连续灌胃给药PSP 22天,实时荧光定量PCR(Q-PCR)检测My D88依赖途径与非依赖途径通路相关基因在小鼠脾脏中的表达;免疫印迹法(Western blot)检测通路中相关蛋白的表达;ELISA检测小鼠眼球血中终端效应因子变化。结果:野生型(WT)组与基因缺陷型(My D88-/-)组小鼠脾脏TLR4信号通路相关基因及蛋白表达均明显升高,My D88-/-组小鼠脾脏中My D88依赖途径的承接因子My D88为零;与WT组相比,My D88非依赖途径通路中TRAM,TRIF的基因及蛋白表达量均无明显变化(P>0.05),共同途径中TRAF6、NF-κB、AP-1的基因及蛋白表达量均明显降低(P<0.05);My D88-/-组眼球血中终端效应因子TNF-α、IFN-γ、IL-2、IL-6及IL-10的分泌量较WT组明显降低(P<0.05)。结论:云芝糖肽对荷瘤小鼠的免疫调节作用可能是通过My D88依赖途径信号通路来实现的。
Objective:To detect the effects of polysaccharopeptide( PSP) on MyD88-dependent signaling pathway in EAC tumor-bearing mice,and explore the immunomodulatory mechanism of PSP. Methods: Ehrlich' s ascites carcinoma( EAC) C57 BL /6mice were used to establish the animal model for solid tumor. Mice were divided into two groups:WT group and MyD88- /-group. After22 days of treatment,quantitative real-time PCR( Q-PCR),Western blot and were used to detect the related gene and protein expression of TLR4 pathway in spleens,ELISA were used to detect the terminal effect factors secretion eyeball blood from each group. Results: Related genes and proteins of TLR4 pathway in spleen were up-regulated significantly from two groups. Compared with WT group,related genes and proteins in MyD88-dependent pathway( MyD88,TRAF6,NF-κB,AP-1) was down-regulated in MyD88- /-group( P〈0. 05). Meanwhile,There was no significant change of the related genes and proteins of MyD88-independent pathway( TRAM,TRIF) in MyD88- /-group( P〉0. 05). The terminal effect factors secretion of IL-2,IL-6,IL-10,TNF-α and IFN-γ in MyD88- /-group were decreased significantly compared with WT group( P〈0. 05). Conclusion: The immunoregulatory effect of PSP on EAC tumor-bearing mice may be implement through the regulation of MyD88-dependent signaling pathway.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2015年第4期480-484,489,共6页
Chinese Journal of Immunology
基金
国家自然科学基金(81274144
81473388)资助