Critical Care Medicine
Effect of activating cannabinoid receptor 2 on sepsis-induced acute lung injury in mice: the role of autophagy
Yuan Qinghong, Liu Qiangsheng, Liu Anpeng, Zheng Fei, Wang Yanlin, Zhang Zongze, Zhan Jia
Published 2018-12-20
Cite as Chin J Anesthesiol, 2018,38(12): 1509-1512. DOI: 10.3760/cma.j.issn.0254-1416.2018.12.027
Abstract
ObjectiveTo evaluate the effect of activating cannabinoid receptor 2(CB2R) on sepsis-induced acute lung injury and the role of autophagy in mice.
MethodsTwenty-four SPF male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups(n=6 each) using a random number table method: sham operation group(group Sham), sepsis group(group Sep), sepsis plus CB2R agonist HU308 group(group Sep+ HU308) and sepsis plus HU308 plus autophagy inhibitor 3-methyladenine group(group Sep+ HU308+ 3-MA). Sepsis was induced by cecal ligation and puncture in anesthetized mice. HU308 2.5 mg/kg was intraperitoneally injected at 15 min after surgery in Sep+ HU308 and Sep+ HU308+ 3-MA groups, and 15 min later 3-MA 10 mg/kg was intraperitoneally injected in group Sep+ HU308+ 3-MA. Lung tissues were obtained at 12 h after surgery and stained with haematoxylin and eosin for examination of the pathological changes which were scored and for determination of the expression of tumor-necrosis factor-alpha(TNF-α), interleukin-18(IL-18) and IL-1β mRNA(by real-time polymerase chain reaction), expression of autophagy-related protein 5(Atg5)(by immuno-histochemistry), and expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1 and p62(by Western blot). The ratio of LC3Ⅱ to LC3Ⅰ(LC3Ⅱ/LC3Ⅰ ratio) was calculated.
ResultsCompared with group Sham, the expression of TNF-α, IL-18 and IL-1β mRNA was significantly up-regulated, and LC3Ⅱ/LC3Ⅰratio and lung injury score were increased in the other three groups, the expression of Beclin-1 was up-regulated, and the expression of p62 was down-regulated in group Sep and group Sep+ HU308, and the expression of p62 was significantly up-regulated in group Sep+ HU308+ 3-MA(P<0.05). Compared with group Sep, the expression of TNF-α, IL-18 and IL-1β mRNA was significantly down-regulated, the expression of Atg5 was up-regulated, and lung injury score was decreased in group Sep+ HU308 and group Sep+ HU308+ 3-MA, LC3Ⅱ/LC3Ⅰratio was increased, the expression of Beclin-1 was up-regulated, and the expression of p62 was down-regulated in group Sep+ HU308, and the expression of Beclin-1 was down-regulated, and the expression of p62 was up-regulated in group Sep+ HU308+ 3-MA(P<0.05). Compared with group Sep+ HU308, the expression of TNF-α, IL-18 and IL-1β mRNA was significantly up-regulated, the expression of Atg5 and Beclin-1 was down-regulated, LC3Ⅱ/LC3Ⅰratio was decreased, the expression of p62 was up-regulated, and lung injury scores were increased in group Sep+ HU308+ 3-MA(P<0.05).
ConclusionActivating CB2R can alleviate acute lung injury in septic mice, and the mechanism may be partially related to enhancing autophagy and reducing inflammatory responses.
Key words:
Receptor, cannabinoid, CB2; Autophagy; Sepsis; Respiratory distress syndrome, adult
Contributor Information
Yuan Qinghong
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Liu Qiangsheng
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Liu Anpeng
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Zheng Fei
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Wang Yanlin
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Zhang Zongze
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Zhan Jia
Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
