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摘要：
目的 研究脑肠肽Ghrelin对急性肺损伤（acute lung injury, ALI）小鼠肺血管功能障碍的作用及机制。 方法 将36只BALB/c小鼠按随机数字表法分为3组（每组12只）：对照组、ALI组、Ghrelin干预组。采用气道内滴注内脂多糖（lipopolysaccharide, LPS）（6 mg/kg）制备ALI模型，6 h后经右侧颈内静脉置入动脉测压管，根据波形确定导管位置后予以记录右心室收缩压（right ventricular systolic pressure, RVSP）变化。测压结束后处死动物，检测肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中细胞因子IL‑6、IL‑17、转化生长因子‑β1（transforming growth factor‑β1, TGF‑β1）和IL‑10。检测肺组织湿/干重比（wet/dry ratio, W/D）、辅助性T细胞（helper T cell 17, Th17）和调节性T细胞（regulatory T cell, Treg）分化情况。Ghrelin干预组于造模前30 min给予皮下注射Ghrelin（20 nmol/kg），余检测同ALI组。 结果 与对照组比较，ALI组小鼠肺RVSP明显升高，W/D增加，肺组织Th17细胞比例升高，Treg细胞比例降低，BALF中Th17相关因子IL‑6、IL‑17、TGF‑β1明显升高，Treg相关细胞因子IL‑10明显降低（P均<0.05）。与ALI组比较，Ghrelin干预组小鼠RVSP明显降低，肺W/D下降，Th17细胞比例及IL‑6、IL‑17、TGF‑β1明显降低，而Treg细胞比例及IL‑10则明显升高（P均<0.05）。 结论 Ghrelin可显著降低ALI小鼠肺血管阻力，降低Th17/Treg比例。结论：ALI小鼠肺血管阻力明显升高，给予Ghrelin预处理后，肺血管阻力明显改善，这同Th17/Treg相关细胞因子的平衡状态被改善相关。
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Abstract: Objective To investigate the effects of brain‑gut peptide Ghrelin on pulmonary vascular dysfunction in mice with acute lung injury (ALI) and related mechanisms. Methods A total of 36 BALB/c mice were divided into three groups according to the random number table method (n=12): a control group, an ALI group and a Ghrelin intervention group. BALB/c mice were instilled with lipopolysaccharide (LPS) (6 mg/kg) in the airway to establish an ALI model. Then, 6 h later, the artery catheter was placed through the right internal jugular vein. The position of the catheter was determined according to the waveform and the changes of the right ventricular systolic pressure (RVSP) were recorded. After the mice were sacrificed, the cytokines interleukin (IL)‑6, IL‑17, transforming growth factor‑β1 (TGF‑β1) and IL‑10 in the alveolar lavage fluid were detected. The dry‑wet ratio (W/D) and the differentiation of T helper cell 17 (Th17) and T regulatory cell (Treg) cells in lung tissue were examined. The Ghrelin intervention group was subcutaneously injected with Ghrelin (20 nmol/kg) 30 min before modeling, and underwent the same examination as the ALI group. Results Compared with the control group, mice with ALI presented remarkable increases in RVSP, lung W/D, the proportion of Th17 cells in lung tissue, and the levels of Th17‑related factor IL‑6, IL‑17, TGF‑β1 in alveolar lavage fluid as well as decreases in the proportion of Treg cells, and Treg‑associated cytokine IL‑10 levels (P<0.05). After pretreatment with Ghrelin, compared with the ALI group, the experimental mice presented significant decreases in RVSP, lung W/D ratio, and the proportion of Th17 cells in the lung tissue, and the levels of IL‑6, IL‑17, and TGF‑β1 as well as increases in the proportion of Treg cells and IL‑10 levels (P<0.05). Conclusions Ghrelin can significantly reduce pulmonary vascular resistance and Th17/Treg ratio in ALI mice.
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