Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.
Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1α.
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三七皂苷通过 HIF-1α 诱导线粒体自噬减轻顺铂诱导的肾毒性
DOI：
10.18632/oncotarget.19900
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发表时间：
2017-11-28
期刊：
影响因子：
--
通讯作者：
Zhong X
中科院分区：
文献类型：
--
作者：
Liang X;Yang Y;Huang Z;Zhou J;Li Y;Zhong X
我们在大鼠模型上研究了缺氧诱导因子-1α在三七总皂苷减轻顺铂所致肾毒性中的作用。顺铂组大鼠血肌酐(Scr)、血尿素氮(BUN)和尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平均升高。在存在或不存在HIF-1α抑制剂2-甲氧基雌二醇(2ME2)的情况下，三七总皂甙可降低Scr、BUN和NAG水平。三七总皂甙还降低了高肾小管损伤评分，这相当于顺铂治疗大鼠的肾小管损伤，而2ME2则加剧了这一损伤。三七总皂苷处理组大鼠肾组织中HIF-1α表达增加，核定位HIF-1α蛋白表达增强。此外，三七总皂甙还可使大鼠肾组织中BNIP3mRNA、LC3-II、BNIP3和Beclin-1蛋白及LC3-II/LC3-I比值升高。这表明三七总皂甙处理增强了HIF-1α，进而增加了自噬。在肾组织的透射电子显微镜中证实了这一点，在三七总皂甙处理的肾组织中显示了自噬小体。这些结果表明，三七总皂甙通过HIF-1α/BNIP3/Beclin-1信号通路增强丝裂原吞噬作用，从而减轻顺铂引起的肾毒性。
We investigated the role of HIF-1α in the mitigation of cisplatin-induced nephrotoxicity by Panax notoginseng saponins (PNS) in a rat model. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG) levels were all elevated in cisplatin treated rats. PNS reduced Scr, BUN and NAG levels in the presence or absence of the HIF-1α inhibitor 2-methoxyestradiol (2ME2). PNS also reduced the high tubular injury scores, which corresponded to renal tubular damage in cisplatin-treated rats and which were exacerbated by 2ME2. Renal tissues from PNS-treated rats showed increased HIF-1α mRNA and nuclear localized HIF-1α protein. Moreover, PNS treatment increased BNIP3 mRNA as well as LC3-II, BNIP3 and Beclin-1 proteins and the LC3-II/LC3-I ratio in rat renal tissues. This suggested that PNS treatment enhanced HIF-1α, which in turn increased autophagy. This was confirmed in transmission electron micrographs of renal tissues that showed autophagosomes in PNS-treated renal tissues. These findings demonstrate that PNS mitigates cisplatin-induced nephrotoxicity by enhancing mitophagy via a HIF-1α/BNIP3/Beclin-1 signaling pathway.
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影响因子：
19.6
作者：
Kim, Jinu;Long, Kelly E.;Padanilam, Babu J.
通讯作者：
Padanilam, Babu J.
DOI：
10.1152/ajprenal.00244.2003
发表时间：
2005-01-01
影响因子：
4.2
作者：
Kairaitis, LK;Wang, YP;Harris, DCH
通讯作者：
Harris, DCH
影响因子：
3.8
作者：
Cleary JM;Mamon HJ;Szymonifka J;Bueno R;Choi N;Donahue DM;Fidias PM;Gaissert HA;Jaklitsch MT;Kulke MH;Lynch TP;Mentzer SJ;Meyerhardt JA;Swanson RS;Wain J;Fuchs CS;Enzinger PC
通讯作者：
Enzinger PC
DOI：
10.1152/ajprenal.00081.2005
发表时间：
2005-11-01
影响因子：
4.2
作者：
Tanaka, T;Kojima, I;Nangaku, M
通讯作者：
Nangaku, M
影响因子：
6.1
作者：
Humanes, Blanca;Camano, Sonia;Lazaro, Alberto
通讯作者：
Lazaro, Alberto