DETA-NONOate对大鼠肝缺血再灌注损伤mGST作用的研究

Effect of DETA-NONOate on mGST in Rat Hepatic Ischemia-Reperfusion Injury

摘要: 目的：探讨一氧化氮供体DETA-NONOate对大鼠肝缺血再灌注(I/R)损伤的保护作用及对微粒体谷胱甘肽S-转移酶(mGST)系统的影响。方法：36只健康雄性SD大鼠随机分为假手术早/晚期组、I/R早/晚期组、DETA干预早/晚期组，建立70%肝缺血1 h再灌注模型，DETA干预组再灌注前5 min尾静脉注射0.2 mg/kg DETA-NONOate。各组分别于再灌注4 h、12 h采集样本，检测血清ALT、AST活性、肝组织病理学损伤、GSH、GSSG、MDA、mGST活性及mGST-1/-2/-3基因表达水平。结果：与同期I/R组相比，DETA干预组血清AST、ALT活性降低，肝组织病理损伤减轻，GSH水平升高，GSSG及MDA水平降低，mGST活性降低，mGST-1/2 (晚期)及mGST-3 (早、晚期) mRNA表达水平升高(均P < 0.05)。与早期(4 h)相比，DETA干预组晚期(12 h) AST水平、mGST活性、GSH水平、GSSG水平均升高，mGST-1、mGST-2、mGST-3mRNA表达水平均上调(均P < 0.05)。结论：DETA-NONOate可通过抑制氧化应激与脂质过氧化、调控mGST系统减轻大鼠肝I/R损伤。

Abstract: Objective: To investigate the protective effect of the nitric oxide donor DETA-NONOate on hepatic ischemia-reperfusion (I/R) injury in rats and its effect on the microsomal glutathione S-transferase (mGST) system. Methods: Thirty-six healthy male SD rats were randomly divided into sham operation early/late groups, I/R early/late groups, and DETA intervention early/late groups. A 70% hepatic ischemia for 1 hour and reperfusion model was established. The DETA intervention group received an intravenous injection of 0.2 mg/kg DETA-NONOate via the tail vein 5 minutes before reperfusion. Blood and liver tissue samples were collected at 4 hours and 12 hours after reperfusion. Serum ALT and AST activities, liver histopathological damage, levels of GSH, GSSG, MDA, mGST activity, and mGST-1/-2/-3 gene expression levels were measured. Results: Compared with the I/R group at the same time point, the DETA intervention group showed decreased serum AST and ALT activities, reduced liver histopathological damage, increased GSH level, decreased GSSG and MDA levels, decreased mGST activity, and increased mRNA expression levels of mGST-1/2 (late stage) and mGST-3 (early and late stages) (all P < 0.05). Compared with the early stage (4 h), the DETA intervention group at the late stage (12 h) showed increased AST level, mGST activity, GSH level, GSSG level, and up-regulated mRNA expression levels of mGST-1, mGST-2, and mGST-3 (all P < 0.05). Conclusion: DETA-NONOate can attenuate rat hepatic I/R injury by inhibiting oxidative stress and lipid peroxidation, and regulating the mGST system.