Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation.
Osthole decreases renal ischemia-reperfusion injury by suppressing JAK2/STAT3 signaling activation.
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DOI：
10.3892/etm.2016.3603
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发表时间：
2016-10
影响因子：
2.7
通讯作者：
Jiang R
中科院分区：
文献类型：
--
作者：
Luo LN;Xie Q;Zhang XG;Jiang R
肾缺血再灌注（I/R）损伤是急性肾损伤的主要原因。肾I/R损伤的发病机制涉及炎症、氧化应激和细胞凋亡。Osthole是一种具有潜在抗炎活性的香豆素衍生物。本研究旨在探讨蛇床子素在肾I/R损伤中的作用及其机制。结扎左肾动脉45 min，再灌注24 h，切除对侧肾，造成肾I/R损伤。将总共70只大鼠随机分为7组（每组n=10）：假手术组、IRI组和蛇床子素（0、5、10、20和40 mg/kg）组。在肾缺血前45 min腹腔注射蛇床子素。再灌注24 h后取血清和肾组织。观察肾功能和组织学变化。采用定量聚合酶链反应（PCR）和酶联免疫吸附试验（ELISA）分别检测肾组织和血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）和白细胞介素-6（IL-6）的mRNA和蛋白表达。Western blot检测p65、p-p65、janus激酶2（JAK 2）、p-JAK 2、信号转导和转录激活因子3（STAT 3）和p-STAT 3蛋白表达水平。结果表明，蛇床子素预处理能显著减轻肾I/R损伤所致的肾功能损害，并呈剂量依赖性，减轻肾组织病理学改变，减轻TNF-α、IL-8、IL-6、p-JAK 2、p-STAT 3和p-p65的表达。蛇床子素和I/R损伤均不影响p65、JAK 2和STAT 3的表达。蛇床子素预处理可通过减轻炎症反应减轻肾I/R损伤，其机制可能与抑制JAK 2/STAT 3活化有关。因此，蛇床子素可能是减轻肾I/R损伤的一种新的实用策略。
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti-inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy. A total of 70 rats were randomly assigned to seven groups (n=10 per group): Sham; IRI; and osthole (0, 5, 10, 20 and 40 mg/kg) groups. Rats were administered intraperitoneally with osthole 45 min prior to renal ischemia. Serum and renal tissue were harvested 24 h after reperfusion. Renal function and histological changes were assessed. In addition, the mRNA and protein expression of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and interleukin-6 (IL-6) in renal tissue and serum were evaluated using quantitative polymerase chain reaction and ELISA assays, respectively. The protein expression levels of p65, p-p65, janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription 3 (STAT3) and p-STAT3 were measured using western blot analysis. The results indicate that osthole pretreatment was able to significantly attenuate the renal dysfunction in a dose-dependent manner, histological changes and the expression of TNF-α, IL-8, IL-6, p-JAK2, p-STAT3 and p-p65 induced by renal I/R injury. However, neither osthole or I/R injury affected the expression p65, JAK2 and STAT3. Osthole pretreatment is able to reduce renal I/R injury by abrogating inflammation and the mechanism is partially involved in suppressing JAK2/STAT3 activation. Thus, osthole may be a novel practical strategy for the mitigation of renal I/R injury.
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作者：
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