Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.
Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.
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成纤维细胞生长因子 2 通过减轻线粒体损伤和促炎信号传导来防止肾缺血/再灌注损伤
DOI：
10.1111/jcmm.13203
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发表时间：
2017-11
影响因子：
5.3
通讯作者：
Zhang JS
中科院分区：
文献类型：
--
作者：
Tan XH;Zheng XM;Yu LX;He J;Zhu HM;Ge XP;Ren XL;Ye FQ;Bellusci S;Xiao J;Li XK;Zhang JS
缺血再灌注损伤（I/RI）是急性肾损伤（阿基）的常见原因。I/RI诱导的肾脏发病机制的分子基础和预防或逆转这种病理过程的措施仍有待解决。碱性成纤维细胞生长因子（FGF 2）被报道具有心肌梗死以及其他几种I/R相关疾病的保护作用。在此，我们提出的证据表明，FGF 2表现出强大的保护作用，对肾组织学和功能损伤的大鼠I/RI模型。FGF 2治疗极大地缓解了I/R诱导的急性肾功能不全，并在很大程度上减弱了I/R诱导的血清肌酐和血尿素氮升高，以及肾脏中TUNEL阳性肾小管细胞的数量。从机制上讲，FGF 2通过减轻几个线粒体损伤参数（包括Bcl 2/Bax表达的促凋亡改变、半胱天冬酶-3活化、线粒体膜电位丧失和KATP通道完整性）显著改善了肾I/RI。值得注意的是，FGF 2的保护作用被KATP通道阻断剂5‐HD显著削弱。有趣的是，单独的I/RI导致FGFR的轻度活化，而FGF 2处理导致更强的受体活化。更重要的是，I/RI后给予FGF 2还通过减少细胞凋亡、抑制损伤相关分子模式分子HMBG 1的释放及其下游炎性细胞因子（如IL-1α、IL-6和TNF α）的激活，对I/RI表现出强大的保护作用。综上所述，我们的数据表明，FGF 2提供了有效的保护，防止I/RI，并通过减弱线粒体损伤和HMGB 1介导的炎症反应，提高动物的生存率。因此，FGF 2有可能用于预防和治疗I/RI诱导的阿基。
Ischaemia‐reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI‐induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R‐induced acute renal dysfunction and largely blunted I/R‐induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL‐positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro‐apoptotic alteration of Bcl2/Bax expression, caspase‐3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5‐HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post‐I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage‐associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL‐1α, IL‐6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1‐mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI‐induced AKI.
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发表时间：
2005-11-01
影响因子：
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通讯作者：
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