Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University. Shenzhen, China.
Department of Anesthesiology, The First People's Hospital of Foshan, 81 North of Rinlan Road, Foshan, China.
Life Sci. 2017 Sep 15;185:30-37. doi: 10.1016/j.lfs.2017.07.018. Epub 2017 Jul 19.
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.
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, p47 and gp91 (two NADPH oxidase subunits), ICAM-1(intercellular adhesion molecule-1) and P-selectin were detected. The levels of oxidative stress markers (SOD, MDA, HO and MPO) and β-hexosaminidase were also measured.
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.
These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs.
肠道缺血再灌注(IIR)通过加重肺氧化应激导致远处的急性肺损伤(ALI)。白藜芦醇通过其抗氧化能力有效减轻 ALI。本研究旨在确定白藜芦醇对 IIR 诱导的 ALI 的影响,并在 IIR 大鼠模型中探讨肥大细胞(MCs)激活的作用。
成年 Sprague-Dawley 大鼠通过夹闭肠系膜上动脉 60min 后再灌注 4 小时来进行 IIR。在 IIR 前 5 天,白藜芦醇以 15mg/kg 的剂量腹腔注射。使用 MCs 稳定剂/抑制剂 cromolyn 钠和脱颗粒剂化合物 48/80 来探索白藜芦醇和 MCs 之间的相互作用。收集肺组织进行病理检测和 MCs 染色。检测肺组织表面活性蛋白-C(SP-C)、胰蛋白酶、p47 和 gp91(两种 NADPH 氧化酶亚基)、细胞间黏附分子-1(ICAM-1)和 P-选择素的蛋白表达。还测量了氧化应激标志物(SOD、MDA、HO 和 MPO)和β-己糖胺酶的水平。
在 IIR 结束时,肺损伤明显增加,与 SP-C 表达降低和肺氧化应激增加有关。IR 后肺部也观察到炎症增加和 MCs 激活。白藜芦醇预处理或 cromolyn 钠抑制 MCs 可预防或逆转所有这些变化。然而,MCs 脱颗粒剂化合物 48/80 降低了白藜芦醇或 cromolyn 钠的这些保护作用。
这些发现表明,白藜芦醇通过稳定 MCs 减少 NADPH 氧化酶蛋白表达和炎症来减轻 IIR 诱导的 ALI。