AMPK抑制剂减轻脂多糖诱导的急性肺损伤

The AMPK Inhibitor Alleviates Lipopolysaccharide-Induced Acute Lung Injury

本研究通过观察腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)抑制剂Compound C对急性肺损伤(acute lung injury,ALI)发生发展的影响,来探讨AMPK在ALI中的病理生理意义。研究中采取脂多糖(lipopolysaccharide,LPS)腹腔注射诱导小鼠ALI,Compound C在腹腔注射LPS前30 min经腹腔注入。在LPS注射后18 h,处死动物、采集肺组织和血浆标本,通过HE染色观察肺组织病理学改变,用ELISA法检测血浆中肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)、白介素6(interleukin 6,IL-6)水平以评估炎症反应程度,检测肺组织中伊文斯蓝的渗出情况以评估微血管通透性,以及检测血浆中乳酸(lactic acid,LA)以评估代谢紊乱程度。Compound C干预可减轻LPS诱导的肺组织病变,下调血浆中TNF-α、IL-6水平,抑制伊文斯蓝渗出,降低乳酸含量。采用AMPK抑制剂Compound C干预可抑制肺内炎症反应、降低肺血管通透性、减轻代谢紊乱,从而缓解肺组织损伤。

To observe the effects of the AMPK inhibitor Compound C on the development of acute lung injury(ALI)and to explore the pathophysiological significance of AMPK in ALI.Lipopolysaccharide(LPS)was injected intraperitoneally to induce ALI in mice,and Compound C was injected intraperitoneally 30 min before LPSexposure.At 18 h after LPS injection,animals were sacrificed and lung tissue and plasma samples were collected.HE staining was used to observe the pathological changes of the lung.ELISA was used to detect plasma levels of TNF-αand IL-6 to evaluate the degree of inflammation.The leakage of Evans blue were detected in lung tissue was examined to evaluate microvascular permeability,and plasma lactic acid(LA)was measured to evaluate the degree of metabolic disorder.Compound C intervention reduced LPS-induced lung pathological changes,down-regulated plasma TNF-α,IL-6 levels,inhibited Evans blue exudation,and reduced lactic acid level.Treatment with the AMPK inhibitor Compound C inhibited the inflammatory response in the lung,reduced the permeability of pulmonary vessels and suppressed the metabolic disturbance,thus alleviating lung tissue damage.