小分子阳离子六肽免疫调节活性及其对小鼠感染模型的治疗作用

Immunomodulatory activity of short catinic hexapeptide and its curative effect on mouse model of infection

目的分析小分子阳离子六肽(short cationic hexapeptides,SP6)免疫调节活性及其对小鼠感染模型的治疗作用。方法经小鼠腹腔分别注射不同剂量SP6(25、5、1μg/只),并设生理盐水对照组,于注射后0.5、1、2、4和7 h对腹腔细胞进行细胞计数;于注射SP6后1 h,经小鼠腹腔给予10%墨汁,0.2 ml/只,收集注射墨汁后0.5、1、2、4和7 h小鼠腹腔细胞,观察吞噬细胞的吞噬作用;于注射SP6后1 h,采血并分离血清,ELISA法检测趋化因子和细胞因子水平。将大肠埃希菌K88、葡萄球菌及巴氏杆菌,分别经小鼠腹腔注射,0.2 ml/只,3 h后,经小鼠皮下注射SP6溶液(25、5、1μg/只),设生理盐水对照组,观察并记录小鼠接种后精神状态及死亡情况。结果 SP6各剂量组小鼠腹腔细胞数量一直高于对照组,直至注射后7 h。SP6各剂量组小鼠腹腔吞噬细胞在0.5 h前开始活化,0.5 h时观察到吞噬细胞包围、吞噬墨汁颗粒,较对照组吞噬细胞活化时间缩短,吞噬能力增强。SP6注射后1 h,中、低剂量组小鼠血清中鼠巨噬细胞来源趋化因子(macrophage derived chemokine,MDC)、淋巴细胞趋化因子(lymphocyte chemokine,LC)、嗜酸性粒细胞趋化因子(eosinophil chemotactic factor,ECF)、趋化因子(chemotactic factor,CF)、IL-1β、IL-4和TNF-α水平与对照组相当或高于对照组(P>0.05);高剂量组小鼠血清中MDC、LC、ECF、CF、IL-1β、IL-4和TNF-α水平均高于对照组,其中LC、IL-1β、TNF-α水平差异有统计学意义(P<0.05)。除巴氏杆菌外,经SP6治疗,高、中、低剂量组小鼠存活数均高于对照组。结论 SP6可调节小鼠免疫反应,对小鼠感染模型有治疗作用。

Objective To analyze the immunomodulatory activity of short cationic hexapeptide（SP6）and its curative effect on mouse model of infection. Methods Mice were injected i. p. with SP6 at various dosages（25, 5 and 1 μg）, using physiological saline as control, of which the peritoneal cells were counted 0. 5, 1, 2, 4 and 7 h respectively. The mice were injected i. p. with 10% ink 1 h after injection with SP6, 0. 2 ml for each, of which the peritoneal cells were collected and observed for phagocytosis. Serum samples were collected 1 h after injection with SP6 and determined for chemokines and cytokines by ELISA. The mice were injected i. p. with Escherichia coli K88, Staphylococcus aureus and Bacillus, 0. 2 ml for each, then injected s. cl with SP6 at various dosages（25, 5 and 1 μg）3 h later, using physiological saline as control, and observed for mental status and death. Results The counts of peritoneal cells of mice injected with SP6 at various dosages were higher than that in control group until 7 h, while the peritoneal cells began to be activated within 0. 5 h, after injection.The ink particles were surrounded and swallowed by the cells 0. 5 h after injection. The time for activation of peritoneal cells were shortened, while the phagocytosis was enhanced, as compared with those in control group. The macrophjage derived chemoline（MDC）, lymphocyte chemokine（LC）, eosinophil chemotactic factor（EGF）, chemotactic factor（CF）, IL-1β, IL-4and TNF-α levels in sera of mice 1 h after injection with SP6 at moderate and low dosages were comparable to or higher than those in control groups（P〉0. 05）. The MDC, LC, ECF, CF, IL-1β, IL-4 and TNF-α levels in sera of mice injected with SP6 at high dosage were higher, of which LC, IL-1β and TNF-α levels were significantly higher, than those in control group（P〈0. 05）. Except those infected with Bacillus, the survival rates of mice infected with E. coli and S. aureus were higher than those in control group after injection with SP6 at various dosages. Conclusion SP6 may regulate the immune response in mice, and has curative effect in mouse model of infection.