Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation
Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation
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高血糖通过诱导慢性氧化应激和炎症加重肝脏缺血再灌注损伤
DOI：
10.1155/2016/3919627
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发表时间：
2016-01-01
影响因子：
--
通讯作者：
Hei, Ziqing
中科院分区：
文献类型：
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作者：
Zhang, Yihan;Yuan, Dongdong;Hei, Ziqing
瞄准探讨高血糖是否加重肝脏缺血再灌注损伤（HIRI）及其机制。方法.对照组和链脲佐菌素诱导的糖尿病Sprague-Dawley大鼠进行部分肝缺血再灌注。相应地评估肝组织学、转移酶、炎性细胞因子和氧化应激。类似地，在高（25 mM）或低（5.5 mM）葡萄糖培养后，使BRL-3A肝细胞经受缺氧/复氧（H/R）。测定了细胞活力、活性氧（ROS）以及B细胞（NF-κ B）中核因子-红细胞2相关因子2（Nrf 2）和核因子κ轻链多肽基因增强子的激活。结果与对照组相比，糖尿病大鼠肝损伤更严重，肝脏炎性细胞因子和氧化应激增加。N-乙酰-L-半胱氨酸（NAC）或夹竹桃苷预处理可改善糖尿病大鼠的HIRI。在高糖暴露后测定过量的ROS产生和随后的Nrf 2和NF-κ B易位。高糖培养组H/R后NF-κ B B易位及其下游细胞因子进一步增加。在低糖培养组中，Nrf 2对其下游抗氧化酶有适当的调节作用，而高糖培养后，H/R对Nrf 2通路没有进一步的诱导作用。结论高血糖会加重HIRI，这可能是由于慢性氧化应激和炎症以及抗氧化系统潜在功能障碍造成的。
Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappa B) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-kappa B translocation were determined after high glucose exposure. NF-kappa B translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.