抗炎多肽对内毒素诱导的小鼠急性肺损伤的保护作用

目的 研究抗炎多肽AF2(antiflammin-2)和重组多肽R2(recombinantant peptide sequence 2)对内毒素(LPS)诱导的小鼠急性肺损伤(ALI)的保护作用,及其对肺组织clara细胞16 000蛋白(CC16)和表面活性蛋白A(SP-A)表达的影响.方法 Balb/c雄性小鼠随机分为5组:对照组,ALI模型组,AF2治疗组,R2治疗组和氢化可的松(HC)治疗组.ALI模型组和各治疗组分别腹腔注射LPS复制小鼠肺损伤模型;治疗组随后注射AF2(2 mg/kg)、R2(2 mg/kg)或氢化可的松(25 mg/kg),对照组和ALI模型组注射等量的生理盐水.在6 h记录动物的呼吸频率;在12 h处死动物,肺组织切片观察肺病理变化;肺组织研磨提取总RNA,半定量法检测CC16和SP-A的表达.结果 (1)各治疗组动物6 h呼吸频率均低于ALI模型组(112±4)次/30 s],分别为AF2治疗组(108±2)次/30 s、R2治疗组(101±2)次/30 s、HC治疗组(96±2)次/30 s,其中R2和HC治疗组与ALI模型组比较,差异有统计学意义.(2)肺组织病理学观察显示AF2、R2对LPS诱导的小鼠ALI肺组织的渗出、炎症细胞浸润有一定的抑制作用,各治疗组病理评分与ALI模型组比较差别均有统计学意义.(3)与ALI模型组比较,AF2治疗组CC16的表达上调,差异有统计学意义,R2和HC治疗组SP-A的表达上调,差异有统计学意义.结论 抗炎多肽AF2和重组多肽R2对内毒素诱导的小鼠ALI有一定的保护作用.

Protective effect of anti-inflammatory peptides on LPS-induced acute lung injury of mouse

Objective To explore the anti-inflammatory effect of antiflammin-2 (AF2) and recombinant peptide sequence 2(R2) on acute lung injury of mouse. To observe the expression of clara cell 16000 protein (CC16) and surfactant protein A (SP-A) in the lung of mouse inoculated with lipopolysaccharide (LPS) and the impact of AF2,R2,and glucocorticoids(hydrocortisone,HC) may have on the expression of the CC16 and SP-A in the lung of mice with acute lung injury. Methods Balb/c mice were inoculated with LPS (5 mg/kg) by intraperitoneal injection to set up ALI mice model. Mice weighed from 15 g to 16 g were grouped into control group, model group and treated groups respectively treated with AF2, R2 or HC. Mice in the control group were injected with physiological saline solution, while mice in the other four groups were inoculated with LPS to induce acute lung injury. Then animals in the treated groups were treated with AF2, R2 or HC each on a dose of 2 mg/kg also through intraperitoneal injection,while those of the control group and the model group, were given equivalent physiological saline solution as a placebo. The respiratory rate of all of these animals were recorded 6 hours after the injection. And at the time point of 12 hour,all the mice were sacrificed for a preparation of the whole lung tissue for the sake of a pathological investigation ,or for extractions of RNA for a semiquantitative analysis of the expression of CC16 and SP-A within the lungs. Results (1) An obvious attenuation of the respiratory rates of the three treated groups were observed when comparing with that of the mice in the model group without any anti-inflammatory treatment. (2) Remarkable extenuation of the extent of intra-alveolar and intersticial hemorrhage and infiltration of inflammatory cells were observed within the treated groups comparing with that of the model group. (3) An attenuate expressions of CC16 or SP-A were observed in the model group,while obvious uptrend of CC16 expression was observed in AF2 treated groups and increase of SP-A expressions were found in R2 and HC treated groups. Conclusion The anti-inflammatory effect of the peptide, AF-2 or R2, has been conformed on ALI mice model induced by LPS.