一种新型乳源抗菌肽β-casein 65临床前应用基础研究

Breast milk which has an effective function on preventing infection is the ideal food for newborns. β-casein65 is a novel endogenous peptides found in preterm milk by Liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) technique. Experiments confirmed that β-casein65 has strong antibacterial activity. Further study found that β-casein65 has cell killing and injury effect on common newborn infection bacteria, e.g. S. aureus, K. pneumoniae and E. coli. Bioinformatics analysis and preliminary experiments suggested that β-casein 65 may damage cell membranes and combine with nuclear material. This study was to investigate the antibacterial activity and mechanism of β-casein 65 against common bacterial infection in premature children on this basis, to assess the therapeutic effect of β-casein65 in vivo through NEC and pneumonia rat model, and to establish the method of β-casein65 large-scale preparation before clinical application. β-casein 65 function have not been reported. If succeed β-casein65 will undoubtedly have a huge potential clinical value.

母乳喂养可有效预防感染，是新生儿最理想的食物。β-casein 65是我们通过串联质谱技术发现的、显著高表达于早产母亲初乳中、功能未知的内源性多肽。实验证实β-casein 65对新生儿感染常见致病菌S. aureus、K. pneumoniae、E. coli均具有杀伤作用；生物信息学分析和预实验提示β-casein 65可破坏细胞膜、结合核内物质发挥作用。本研究拟进一步论证β-casein 65抗新生儿常见致病菌功能并探索其杀伤机制；在体评估β-casein 65对大鼠NEC、肺炎动物模型的治疗作用；初步建立β-casein 65临床应用前大规模制备方法。β-casein 65功能未见报道，若研究成功，无疑具有巨大的潜在临床应用价值。

母乳可有效预防感染，是新生儿最理想的食物。β-casein65是我们通过串联质谱技术发现的、显著高表达于早产母亲初乳中、功能未知的内源性多肽。本项研究证实β-casein 65是对E. coli和S. aureus具有较强抗菌活性的母乳来源的新型抗菌肽，通过体外抑菌实验、形态学观察、检测与DNA/RNA核酸类物质结合等，明确了β-casein 65可以通过破坏细胞膜发挥抑菌作用的机制。在体评估结果显示β-casein 65对大鼠NEC模型具有一定的治疗效果，可以显著改善肠坏死的表型；组织切片HE染色后，β-casein 65组肠绒毛充血、水肿较轻，肠上皮细胞数量增加；增殖相关标志物PCNA免疫组化染色结果也证实，β-casein 65可以促进肠上皮细胞修复，对NEC模型具有一定治疗作用。本研究获得了β-Casein 65抗菌作用及可能机制的证据，将有助于为早产儿感染预防和治疗提供新的线索和方向。