Resveratrol Attenuate Lung Injury Induced By Cardiopulmonary Bypass In Rats

Cardiopulmonary bypass is an important part of the open-heart surgery with improvement of technology, complications and mortality after open heart surgery decreased significantly, but CPB related to organ damage still plagued the majority of clinicians, clinical studies have shown that acute lung injury (ALI)is the most common complication after CPB, about2%of patients may develop acute respiratory distress syndrome, the mortality rate as high as50%-91.6%. Domestic and international studies have shown that CPB can induce the production and release of inflammatory mediators, which cause a series of cell activation, lead to intensified inflammatory response and acute lung injury. In recent years, studies suggest that SIRT1and NF-κB played a particular role in the regulation of inflammation. However, the role of SIRT1and NF-κB on CPB-induced inflammation is largely unknown.Due to the "French paradox ", Researches on Resveratrol (Res) demonstrated that resveratrol is SIRT1activator and has anti-oxidation, anti-aging, anti-tumor and significant anti-inflammatory effects.In this study, we hypothesis that SIRT1downregulation could be inhibited by pretreatment with resveratrol in a rat CPB model,thus result in the reduction of cytokines expression. Therefore, resveratrol might protect lung from inflammatory injury after CPB.Part1:Study of lung injury in a rat cardiopulmonary bypass model ObjectiveThis study was designed to test the mechenisim of CPB-induced lung inflammatory injury in a rat model.Materials and methodsMale Sprague-Dawley rats were randomly divided into two groups (n=12):Sham group and CPB group. Blood samples were collected at the beginning, at the end of CPB, and at1h,2h,12h post-operation. At12hours after CPB, the bronchoalveolar lavage fluid was harvested from the left lung and then used for tumor necrosis factor-a (TNF-a). interleukin-6(IL-6) and matrix metalloproteinase-9(MMP-9). The right lung was used for microscopic examination, p-IkBa and SIRT1determination.ResultsRespiratory index in resveratrol pretreatment group were significantly lower that of control group. Resveratrol decreased p-IkBa expression and increased SIRT1expression after CPB. As compared with control group, the level of TNF-α、IL-6and MMP-9in serum, bronchoalveolar lavage fluid and lung tissues were decreased in resveratrol pretreated group. The anti-inflammatory effect of resveratrol appeared a dose dependent manner.Microscopic findings in the lung specimens showed that animals in CPB group had severe lung parenchyma injury, alveolar hemorrage and neutrophil infiltration.ConclusionsOur experiment showed that CPB would induce lung injury in a rat model, which is confirmed by both biochemical marker and morphology examinations.Part two:Resveratrol attenuated lung injury induced by cardiopulmonary bypass in a rat modelObjectiveThe main aims of our study were to explore whether pretreated with resveratrol would attenuated lung injury in a rat CPB model.Materials and methodsMale Sprague-Dawley rats were randomized into three groups (n=12):CPB (group Control); CPB+low dose resveratrol (50mg/kg/d,L-Res); CPB+high dose resveratrol (100mg/kg/d,H-Res). Blood samples were collected at the beginning, at the termination of CPB, and at1h,2h,12h post-operation. At12hours after CPB, the bronchoalveolar lavage fluid was harvested from the left lung for measurement of TNF-α、IL-6and MMP-9. The right lung was used for microscopic examination, p-IkBa and SIRT1determination.ResultsRespiratory index in Resveratrol treated groups was significant lower than that of control group. We observed that resveratrol reduced CPB-induced p-IkBa expressions in CPB groups whereas elvaluated SIRT1expression. The levels of tumor necrosis factor-a,interleukin-6,and matrix metalloproteinase-9in serum,, bronchoalveolar lavage fluid and lung tissues increased in CPB groups, whereas pretreated with resveratrol reduced these inflammatory marks in a dose-dependent manner. Furthermore, pretreatment with resveratrol had a lower lung injury score.ConclusionsThese findings suggested that resveratrol inhibited CPB-induced p-IkBa upregulation, evaluated SIRT1expression, efficaciously reduced pulmonary inflammatory injury after CPB.