ObjectiveTo establish a lung ischemia-reperfusion (I/R) model in C57BL/6 mice, and to study the role of cannabinoid 2 (CB2) receptor in lung I/R injury by pretreatment with CB2 receptor agonist JWH-133 and antagonist AM-630.
MethodsForty-eight mice were randomly divided into the following 4 groups: Sham group, I/R group, JWH133 group and AM630+JWH133 group, with 12 mice in each group.In Sham group, the hilum was separated by thoracotomy without clamping, and then ventilated for 3 hours.In the I/R group, after thoracotomy, the left pulmonary hilum was clamped with vascular forceps for 1 hour, and reperfusion was performed for 2 hours after release.JWH133 group: JWH-133 (5 mg/kg) was intraperitoneal injected 5 minutes after clamping of the pulmonary hilum, and the left hilum was occlusioned for 1 hour of ischemia, and then reperfusion was performed for 2 hours after release; AM630+JWH133 group.AM-630 (2 mg/kg) was intraperitoneally injected 30 minutes before JWH-133 injection, and the rest was the same as JWH133 group.Each group was then randomly divided into two subgroups for blood gas analysis, lung wet-dry ratio determination, lung histopathological examination and apoptosis-related proteins (Bcl-2, Bax, caspase-9) detection.
ResultsCompared with I/R group, oxygenation index was increased, lung wet-dry ratio and pathological score of lung injury were significantly decreased in JWH133 group, lung tissue structure was improved by HE staining, the expression of Bcl-2 was significantly increased, and the expression of caspase-9 and Bax was significantly decreased.These effects were reversed by intraperitoneal injection of AM-630 prior to JWH-133 administration.
ConclusionsIntraperitoneal injection of CB2 receptor agonist JWH-133 can inhibit the apoptosis of lung tissue in mice, and obviously alleviate the lung ischemia-reperfusion injury.Apoptosis may be involved in activating CB2 receptor-mediated lung protection.
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