锡原卟啉激活oxidant-dependent NRF2-cytoprotective通路和减轻急性肾损伤。

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约翰逊ACM, Delrow JJ,急变RA

锡原卟啉激活oxidant-dependent NRF2-cytoprotective通路和减轻急性肾损伤。

Transl研究》2017年8月,186:1-18。doi: 10.1016 / j.trsl.2017.05.005。2017年5月19日Epub。

PubMed ID

28586635 (在PubMed

]

文摘

锡原卟啉(SnPP),一个血红素氧合酶(HO)抑制剂,同时也防止各种形式的急性肾损伤(AKI)。本研究寻求潜在的潜在机制。cd -小鼠接受静脉注射SnPP, 4-18小时后由多种肾脏生化,组织学,基因组评估。肾阻力ischemic-reperfusion受伤(IRI)也寻求。SnPP迅速被肾脏,局限于近端小管。瞬变抑制肾血红素合成(δaminolevulinic酸合酶表达下降),增加了2.5倍“催化”铁水平和氧化剂应激导致(减少谷胱甘肽;增加丙二醛,和蛋白质羰基含量)。Nrf2核易位(大约2 x Nrf2增加;通过酶联免疫吸附试验检测,西方墨点法),相应的大约20 Nrf2-sensitive基因激活(RNA-Seq)观察。由18个小时SnPP注射后,标志着保护IRI出现。 This represented "preconditioning", not a direct SnPP effect, given that SnPP administered at the time of IRI exerted no protective effect. The importance of transient oxidant stress in SnPP "preconditioning" was exemplified by the following: (1) oxidant stress induced by a different mechanism (myoglobin injection) recapitulated SnPP's protective action; (2) GSH treatment blunted SnPP's protective influence; (3) SnPP raised cytoprotective heavy chain ferritin (Fhc), a response enhanced by exogenous Fe injection; and (4) SnCl2, a approximately 35- to 50-fold HO-1 inducer (not inhibitor) evoked neither oxidant stress nor mitigated IRI (seemingly excluding HO-1 activity in SnPP's protective effect). SnPP specifically accumulates within proximal tubule cells; transient "catalytic" Fe overload and oxidative stress result; Nrf2-cytoprotective pathways are upregulated; and these changes help protect against ischemic AKI.

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锡原卟啉IX