中科院昆明动物研究所研究员张云课题组发现，天然抗菌肽具有选择性免疫激活和调节功能，对败血症有良好的预防和保护作用。相关研究近日在线发表于美国《医药化学杂志》。

传统抗生素的滥用导致临床上出现各种耐药菌株，严重危害人类健康。在与致病菌变异竞争的过程中，自然界各种来源的抗菌肽成为人们研发新型抗感染药物的新希望，但目前人们对抗菌肽的认识和研究仍集中于其直接杀灭细菌生长的效应上。

张云认为，败血症是由细菌感染引起的，伴随有全身性炎症反应综合症状的一种危重疾病。病原微生物感染诱导促炎症因子大量释放，导致多种重要器官衰竭，具有较高死亡率。

“为此，我们在前期大量研究工作和相关发明专利——爬行动物cathelicidin抗菌肽及衍生物及其应用的基础上，深入揭示该抗菌肽在体内外具有选择性的免疫激活作用。”张云说，在各种标准和临床耐药菌株诱导的败血症动物模型中，cathelicidin肽选择性地激活体内天然免疫响应，在不引起大量有害炎症因子激活的同时，通过p38 MAPK信号通路选择性地刺激炎症抑制细胞因子、免疫细胞趋化因子的表达和释放，对全身性和致死性败血症具有良好的预防和保护作用。

同时，该研究还提示目前已知的大量天然抗菌肽分子的免疫调节和炎症抑制功能有待深入研究和挖掘，为其用于临床感染性和免疫性疾病治疗药物的研发提供了新思路。（来源：中国科学报 张雯雯）

Naturally Occurring Antimicrobial Peptide OH-CATH30 Selectively Regulates the Innate Immune Response To Protect against Sepsis

Sepsis, which is a systemic inflammatory response that follows a bacterial infection, has a high mortality rate and limited therapeutic options. Here we show that the antimicrobial peptide OH-CATH30, which naturally occurs in snake, selectively regulates the innate immune response to protect mice from lethal sepsis. The administration of OH-CATH30 significantly improves the survival rate of mice infected by antibiotic-susceptible and -resistant pathogens, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. OH-CATH30 selectively up-regulates the production of chemokines and cytokines without harmful immune response. Recruitment of monocytes, macrophages, and neutrophils to the infection site is pivotal to the protective capacity of OH-CATH30. Furthermore, the alternative activation of the innate immune response by OH-CATH30 depends on p38 mitogen-activated protein kinase signaling. Taken together, our study demonstrates that OH-CATH30, a naturally occurring antimicrobial peptide, selectively stimulates the innate immune response to protect against sepsis.

原文链接：http://pubs.acs.org/doi/full/10.1021/jm401134n