Xiaolei Huang1, Weicheng Zhao2, Dan Hu3, Xue Han4, Hanbin Wang5, Jianyu Yang1, Yang Xu1, Yuantao Li1, Weifeng Yao6, Chaojin Chen7. 1. Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University. Shenzhen, China. 2. Department of Anesthesiology, The First People's Hospital of Foshan, 81 North of Rinlan Road, Foshan, China. Electronic address: zwcheng@fsyyy.com. 3. Department of Ophthalmology, The First People's Hospital of Foshan, China. 4. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. 5. Department of Anesthesiology, The First People's Hospital of Foshan, 81 North of Rinlan Road, Foshan, China. 6. Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. 7. Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: chchjin@mail2.sysu.edu.cn.
Abstract
BACKGROUND: Intestinal ischemia/reperfusion (IIR) leads to acute lung injury (ALI) distally by aggravating pulmonary oxidative stress. Resveratrol is effective in attenuating ALI through its antioxidant capacity. This study aimed to determine the effects of resveratrol on IIR-induced ALI and to explore the role of mast cells (MCs) activation in a rat model of IIR. METHODS: Adult Sprague-Dawley rats were subjected to IIR by occluding the superior mesenteric artery for 60min followed by 4-hour reperfusion. Resveratrol was intraperitoneally injected at a dose of 15mg/kg for 5days before IIR. MCs stabilizer/inhibitor cromolyn sodium and degranulator compound 48/80 were used to explore the interaction between resveratrol and MCs. Lung tissues were collected for pathological detection and MCs staining. Pulmonary protein expression of surfactant protein-C (SP-C), tryptase, p47phox and gp91phox (two NADPH oxidase subunits), ICAM-1(intercellular adhesion molecule-1) and P-selectin were detected. The levels of oxidative stress markers (SOD, MDA, H2O2 and MPO) and β-hexosaminidase were also measured. RESULTS: At the end of IIR, lung injury was significantly increased and was associated with decreased expression of SP-C and increased lung oxidative stress. Increased inflammation as well as activation of MCs was also observed in the lungs after IIR. All these changes were prevented or reversed by resveratrol pretreatment or MCs inhibition with cromolyn sodium. However, these protective effects of resveratrol or cromolyn sodium were reduced by MCs degranulator compound 48/80. CONCLUSIONS: These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs.
BACKGROUND: Intestinal ischemia/reperfusion (IIR) leads to acute lung injury (ALI) distally by aggravating pulmonary oxidative stress. Resveratrol is effective in attenuating ALI through its antioxidant capacity. This study aimed to determine the effects of resveratrol on IIR-induced ALI and to explore the role of mast cells (MCs) activation in a rat model of IIR. METHODS: Adult Sprague-Dawley rats were subjected to IIR by occluding the superior mesenteric artery for 60min followed by 4-hour reperfusion. Resveratrol was intraperitoneally injected at a dose of 15mg/kg for 5days before IIR. MCs stabilizer/inhibitor cromolyn sodium and degranulator compound 48/80 were used to explore the interaction between resveratrol and MCs. Lung tissues were collected for pathological detection and MCs staining. Pulmonary protein expression of surfactant protein-C (SP-C), tryptase, p47phox and gp91phox (two NADPH oxidase subunits), ICAM-1(intercellular adhesion molecule-1) and P-selectin were detected. The levels of oxidative stress markers (SOD, MDA, H2O2 and MPO) and β-hexosaminidase were also measured. RESULTS: At the end of IIR, lung injury was significantly increased and was associated with decreased expression of SP-C and increased lung oxidative stress. Increased inflammation as well as activation of MCs was also observed in the lungs after IIR. All these changes were prevented or reversed by resveratrol pretreatment or MCs inhibition with cromolyn sodium. However, these protective effects of resveratrol or cromolyn sodium were reduced by MCs degranulator compound 48/80. CONCLUSIONS: These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs.