目的·探讨阻断大麻素受体1（cannabinoid receptor 1，CB1）对小鼠急性肺损伤（acute lung injury，ALI）的影响及其潜在的分子机制。方法·将40只小鼠随机分为空白对照组、AM281（CB1拮抗剂）对照组、脂多糖（lipopolysaccharide，LPS）组、LPS＋AM281组，每组10只。利用LPS诱导建立小鼠ALI模型。经苏木精-伊红（hematoxylin and eosin，H-E）染色观察各组小鼠肺组织病理表现并计算炎症评分。通过反转录和实时荧光定量聚合酶链反应（real-time fluorescent quantitative polymerase chain reaction，qPCR）检测各组小鼠肺巨噬细胞M1型标志物［肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）、IL-12］和M2型标志物［精氨酸酶（arginase，Arg）、甘露糖受体C型2（mannose receptor，C type 2，Mrc2）、巨噬细胞半乳糖型凝集素1（macrophage galactose-type lectin 1，Mgl1）］的mRNA水平。体外培养人髓系白血病单核细胞THP-1，通过免疫荧光技术检测THP-1细胞中CB1和CB2的表达，并在进一步阻断CB1及抑制G_αi/o/RhoA信号通路后，检测M1型标志物的mRNA水平。结果·LPS组小鼠肺组织损伤明显，炎症评分明显升高；阻断CB1后，与LPS组相比，LPS＋AM281组小鼠肺损伤得到改善，表现为肺泡壁毛细血管充血改善、肺间质及肺泡腔内炎症细胞浸润减少，炎症评分下降（P=0.007）。与对照组相比，LPS组小鼠肺组织中M1型标志物水平上调，而在阻断CB1后巨噬细胞极性发生改变，M1/M2比例发生反转（均P<0.05）。体外研究发现，巨噬细胞表达CB1和CB2，利用花生四烯基-2-氯乙酰胺（arachidonyl-2-chloroethylamide，ACEA）激活CB1可上调M1型标志物的表达，阻断CB1及选择性抑制G_αi/o/RhoA信号通路后，M1型标志物的表达均明显下调（均P<0.05）。结论·CB1在ALI中通过Gα_i/o/RhoA信号通路促进巨噬细胞向M1极化，阻断CB1可改善肺损伤。

Objective ·To explore the effects and potential molecular mechanisms of blocking cannabinoid receptor 1 (CB1) in acute lung injury (ALI) in mice. Methods ·Forty mice were randomly divided into blank control group, AM281 (CB1 antagonist) control group, lipopolysaccharide (LPS) group, and LPS＋AM281 group, with ten mice in each group. ALI models were induced by LPS. The pathological manifestations of lung tissues were observed in each group of mice by hematoxylin and eosin (H-E) staining and the inflammation scores were calculated. The mRNA levels of M1 markers [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12] and M2 markers [arginase (Arg), mannose receptor, C type 2 (Mrc2), macrophage galactose-type lectin 1 (Mgl1)] in lung macrophages were measured by reverse transcription and real-time fluorescence quantitative polymerase chain reaction (qPCR). Human myeloid leukemia monocytes THP-1 cells were cultured in vitro, and the expression of CB1 and CB2 in THP-1 cells was detected by immunofluorescence. After further blocking CB1 and inhibiting the Gα_i/o/RhoA signaling pathway, the mRNA levels of M1 markers were assessed. Results ·The LPS group showed significant lung tissue damage and a significant increase in inflammation scores in mice. After blocking CB1, compared with the LPS group, the LPS＋AM281 group of mice showed improvements in lung injury, manifested as improved congestion of alveolar wall capillaries, reduced infiltration of inflammatory cells in the lung interstitium and alveolar cavity, and a decreased inflammation score (P=0.007). Compared with the control group, the levels of M1 marker in the lung tissue of the LPS group were upregulated, while the polarization of macrophages changed and the M1/M2 ratio was reversed after blocking CB1 (all P<0.05). In vitro studies found that macrophages expressed CB1 and CB2. Activation of CB1 by arachidonyl-2-chloroethylamide (ACEA) upregulated the expression of M1 markers. Blocking CB1 and selectively inhibiting Gα_i/o/RhoA signaling significantly downregulated M1 markers (all P<0.05). Conclusion ·CB1 promotes the polarization of macrophage towards the M1 phenotype through the Gα_i/o/RhoA signaling pathway in ALI, and blocking CB1 can improve lung injury.