GHRP-2对sepsis诱导的急性肺损伤大鼠的保护作用研究

Protective effects of GHRP-2 on sepsis induced acute lung injury

目的观察Ghrelin激动剂GHRP-2对sepsis诱导产生的急性肺损伤（ALI）大鼠的保护作用。方法SD大鼠随机分为四组，生理盐水对照组，ALI组，GHRP-2治疗组和GH对照组，每组12只。通过静脉注射7．5mg／kgLPS建立ALI模型，ALI模型制备前30min皮下注射GHRP-2100μg／kg或等体积生理盐水。LPS注射后6h处死动物，取动脉血进行血气分析，取肺组织病理学改变，髓过氧化物酶（MPO）水平，肺湿重／肺干重（W／D）。取支气管肺泡灌洗液（BALF）观察其中蛋白含量，细胞计数以及炎性介质TNF—α和IL-6的水平。结果脂多糖（LPS）注射后6h，模型大鼠出现明显的氧合障碍，MPO水平，肺W／D比值明显高于生理盐水对照组，而给予GHRP-2处理的ALI大鼠上述各指标则显著低于ALI组。ALI组BALF中蛋白含量，细胞计数和炎性介质水平明显高于正常对照组，而给予GHRP-2预处理后的Au大鼠则出现明显降低（P〈0．05）。结论静脉注射LPS可成功诱导Au模型，经GHRP-2预处理后，ALI可显著改善，提示GHRP-2对sepsis诱导的ALI大鼠具有保护作用。

Objective To investigate the effects of GHRP-2 on sepsis induced acute lung injury （ALI） rats. Methods SD rats weighting 200-250 g were randomly divided into four groups （ n = 12 per group） ~saline control group, ALI group, GHRP-2/ALI group,GHRP-2 control group. ALl was induced by administering 7.5 mg/kg lipopolysaccharide （LPS） via vein. The rats were subcutaneously treated with 100 μg/kg GHRP-2 30 min before LPS administration. Rats were sacrificed at 6 h after LPS administration, blood were obtained to observe blood gas, lung tissue were used to examined lung pathology changes, lung edema and myeloperoxidase level. Moreover, protein content, cell count and inflammatory cytokines TNF-α and IL-6 levels were detected in BALF. Results 6 h after LPS administration, rats appeared obvious decreased oxygenation, meanwhile, lung injury score, MPO level and W/D ratio were significantly enhanced in ALI rats compared with saline group （ P 〈0.05）, GHRP- 2 pretreatment obviously decreased these lung injury indexes. In BALF, ALI rats has obviously protein level, cell count and inflammatory eytokines level, however, GHRP-2 pretreatment significantly reduced these indexes in BALF. No obvious difference in saline control group and GHRP-2 control group. Conclusions GHRP-2 could decrease the inflammation response and prevent the development of ALI which caused by LPS which suggest a potential therapy agent for ALI.