关键词: 腺苷A2b受体, 肾缺血再灌注, 急性肺损伤, PI3K/Akt 信号通路

Abstract: Objective To study the protective effect and mechanisms of adenosine A2b receptor activation on lung injury induced by renal ischemia-reperfusion. Methods 30 male C57BL /6J mice were randomly divided into control group (group C), ischemia-reperfusion group (I/R group), ischemia-reperfusion+A2bR agonist Bay606583 group (I/R+Bay group, 1mg/kg Bay i.p. 15min before sugery), ischemia-reperfusion + A2bR agonist Bay606583 +Akt inhibitor LY294002 group (I/R+Bay+LY group, 1mg/kg Bay+7.5 mg/kg LY i.p. 15min before sugery), ischemia-reperfusion + A2bR antagonist MRS1754 group (I/R+MRS group, 1mg/kg MRS i.p. 15min before sugery). After renal ischemia-reperfusion surgery and sham operation for 24 hours, blood samples were taken for renal function test (serum creatinine, blood urea nitrogen); the expression of A2bR mRNA in lung tissue of mice was detected; the expression of p-Akt and A2bR in lung tissue was detected by Western blot. The ratio of wet weight/dry weight and the concentrations of protein, TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) of each group were detected. Moreover, pathological changes in lung tissue were observed and arterial blood was acquired to perform the arterial blood gas analysis. Results The serum creatinine and blood urea nitrogen was increased and the mRNA expression of A2bR was significantly decreased after renal ischemia-reperfusion (P <0.05), and the protein level of p-Akt was also decreased obviously after reperfusion. In addition, compared with the control group, the ratio of wet weight / dry weight, the alveolar lavage fluid protein, TNF-α and IL-6 concentrations were significantly increased (P <0.05), and the lung pathological injury score and oxygenation level were significantly damaged seriously (P< 0.05), and 1 mg/kg Bay606583 preoperative intraperitoneal injection can significantly alleviate the above damage and increase the expression of p-Akt, however this effect disappeared after the application of the Akt inhibitor LY294002. Conclusions Activation of adenosine A2b receptors attenuates the inflammatory response of lung tissue, which ultimately reducing lung tissue damage and improving oxygenation after renal ischemia-reperfusion and this effect may be caused by enhancing the PI3K/Akt signaling pathway.

Key words: adenosine A2b receptor, renal ischemia-reperfusion, acute lung injury, PI3K/Akt signal pathway