基因工程鲎素对小鼠非特异性免疫的影响及作用机制

抗菌肽具有抗感染和介导宿主天然免疫防御作用,是理想的抗生素替代物,实验室前期用研发的基因工程鲎素(TPI)对小鼠金黄色葡萄球菌感染模型开展的治疗效果显示,小鼠感染模型肺部及其他脏器中菌含量明显减少,肺部的病理变化减轻,治疗效果较好。本试验在此基础上,从宿主天然免疫防御的角度开展了TPI对小鼠非特异免疫功能的影响及机制研究。用滴鼻的方式给小鼠使用TPI,测定不同剂量TPI对小鼠体征指标,包括:体质量、肺廓清指数、脾脏指数的影响。用腹腔注射的方式给小鼠使用TPI,测定非特异性免疫相关指标,包括:小鼠单核细胞和巨噬细胞的吞噬能力、小鼠β-防御素2(mBD-2)和小鼠胸腺肽β4的表达水平,结果显示与对照组相比,TPI可提高小鼠增重,可显著提高小鼠的巨噬细胞吞噬能力及廓清指数;可上调小鼠脏器中mBD-2和小鼠胸腺肽β4的表达水平,增强宿主防御能力,激活机体非特异性免疫,提示TPI不但能直接杀伤病原体,还能够激活和协同宿主防御肽共同发挥非特异免疫作用。

Effect of tachyplesin I on nonspecific immune level in mice

Antimicrobial peptide has the function of anti-infection and mediating the host natural immune defense.It is an ideal antibiotic substitute.The gene engineering tachyplesin I(TPI) showed the therapeutic effect on the mouse model of Staphylococcus aureus pulmonary infection.TPI can effectively remove Staphylococcus aureus in vivo and reduce the pathological changes of the mouse lung,so TPI has a good therapeutic effect.On the basis,this study was carried out to evaluate,in the perspective of natural immune defense of the host,the effect of TPI on the nonspecific immune function of mice infected with Staphylococcus aureus.The body weight,lung clearance index,spleen index,and nonspecific immune related indexes were measured,also including the phagocytic ability of monocyte and macrophage,the gene and protein expression level of mouse β-defensin 2(mBD-2) and mouse thymosin 4(tmsb4 x) Ring.The results showed that compared with the normal saline group,the weight of mice in each TPI dosage groups was increased,the phagocytic capacity and clearance index of macrophages in the middle dosage group were significantly increased,and TPI stimulated the protein and gene levels of mBD-2 and tmsb4 x in mice,and the host defense ability was significantly enhanced.Because these factors played an important role in killing pathogenic bacteria,it is suggested that TPI can cooperate with host defense peptide to play an anti-infective role.This study provides a reference and theoretical basis for the clinical application of TPI as a microecological agent.