Nrf2-ARE信号通路在间歇性低氧胰腺组织中的作用及银杏叶提取物的干预机理

目的 观察Nrf2-ARE信号通路对慢性间歇性低氧胰腺组织的影响及银杏叶提取物对其的干预机理。方法 选取C57BL/6雄性小鼠、Nrf2基因敲除型雄性小鼠各54只，随机分为常氧对照组1、2，间歇性低氧组1、2，Nrf2激活剂组，抗体阻断组，银杏叶提取物（EGB）低、中、高浓度组，每组6只。除常氧对照组外，其余各组小鼠循环给予氮气和氧气建立间歇性低氧模型。Nrf2激活剂组腹腔注射莱菔硫烷，抗体阻断组腹腔注射抗Nrf2抗体，EGB低、中、高浓度组分别予EGB50、100、200 mg/（kg·d）灌胃，常氧对照组予等量生理盐水干预。干预10周后用Western-Blot和RT-PCR分别检测胰腺组织中Nrf2、HO-1、NQO1、γ-GCS蛋白和mRNA的表达水平。结果 野生型小鼠中，与间歇性低氧组比较，Nrf2、HO-1、NQO1和γ-GCS在Nrf2激活组、EGB高浓度组中蛋白和mRNA表达均升高，在抗体阻断组中蛋白和mRNA表达均降低（P＜0.05）；基因敲除型小鼠中，与间歇性低氧组比较，HO-1在Nrf2激活组、EGB高浓度组中蛋白和mRNA表达均升高（P＜0.05）；NQO1在EGB中浓度组中蛋白和mRNA表达均升高（P＜0.05）；γ-GCS在EGB中、高浓度组中蛋白和mRNA表达均升高（P＜0.05）。结论 间歇性低氧导致的氧化应激参与了OSAS的发生发展过程，可能是OSAS胰腺组织损伤的主要病理生理机制。EGB通过促进Nrf2-ARE信号通路介导的抗氧化反应，保护胰腺组织免受间歇性低氧诱导的损伤。

Role of Nrf2-ARE Signaling Pathway in Intermittent Hypoxic Pancreatic Tissue and Intervention Mechanism of Ginkgo Biloba Extract

Objective To observe the effect of Nrf2-ARE signaling pathway on chronic intermittent hypoxic pancreatic tissue and the intervention mechanism of Ginkgo biloba extract. Methods In that C57BL/6 male mice,54 of the Nrf2 gene knock-out male mice were selected,randomly divided into normoxic control group 1, 2, intermittent hypoxia group 1, 2, Nrf2 activator group, antibody blocking group, Ginkgo biloba extract (EGB) low, medium and high concentration groups, 6 in each group. Except the normoxic control group, the other groups of mice were cyclically given nitrogen and oxygen to establish an intermittent hypoxia model. The Nrf2 activator group was injected intraperitoneally with lymesulfane, and the antibody blocking group was intraperitoneally injected with anti-Nrf2 antibody. The EGB low, medium, and high concentration groups were given intragastrically with EGB50, 100, and 200 mg/(kg·d). Equal volume of saline intervention. After 10 weeks of intervention, Western-Blot and RT-PCR were used to detect the expression levels of Nrf2, HO-1, NQO1, γ-GCS protein and mRNA in pancreatic tissue, respectively.Results In wild-type mice, compared with the intermittent hypoxia group, Nrf2, HO-1, NQO1, and γ-GCS were found in the Nrf2 activated group,the protein and mRNA expressions were increased in the EGB high concentration group, and the protein and mRNA expressions were decreased in the antibody blocking group (P<0.05).In the knockout mice, compared with the intermittent hypoxia group, HO-1 protein and mRNA expression were increased in the Nrf2 activated group and EGB high-concentration group (P<0.05);The protein and mRNA expressions of NQO1 in the EGB medium concentration group were increased (P<0.05); the γ-GCS protein and mRNA expression were increased in the EGB medium and high concentration groups (P<0.05). Conclusion Oxidative stress caused by intermittent hypoxia is involved in the development of OSAS and may be the main pathophysiological mechanism of OSAS pancreatic tissue injury. EGB protects pancreatic tissue from intermittent hypoxia-induced damage by promoting the antioxidant response mediated by the Nrf2-ARE signaling pathway.