Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β.
Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β.
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DOI：
10.1038/srep36698
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发表时间：
2016-11-18
影响因子：
4.6
通讯作者：
Gong R
中科院分区：
文献类型：
--
作者：
Jiang C;Zhu W;Yan X;Shao Q;Xu B;Zhang M;Gong R
急性肾损伤（AKI）对临床实践仍然具有挑战性，并且存在发展为进行性慢性肾病（CKD）的风险，而目前尚无明确的治疗方法。丹参酮 IIA 是中草药丹参的活性成分，因其显着的器官保护活性而在亚洲被广泛使用。然而，它对已发生的 AKI 的影响仍然未知。在叶酸诱导的 AKI 小鼠中，延迟使用丹参酮 IIA 治疗，在损伤后早期或晚期开始治疗，肾损伤标志物的肾表达减少，细胞凋亡减少，肾功能障碍得到改善，同时 AKI 向 CKD 转变的组织学体征减轻，包括间质纤维化和肾小管萎缩，肾小管间质炎症浸润得到改善，巨噬细胞偏向 M2 极化。从机制上讲，丹参酮 IIA 减弱了糖原合成酶激酶 (GSK)3β 的过度活性和其下游丝裂原激活蛋白激酶的过度激活，这些激酶主要与肾纤维形成和炎症有关。 GSK3β 的抑制可能是介导丹参酮 IIA 治疗活性的关键机制，因为硝普钠（一种 GSK3β 激活剂）在很大程度上抵消了其肾脏保护作用。在验证性研究中，丹参酮 IIA 的救援治疗同样可以改善小鼠缺血/再灌注引起的肾脏破坏。我们的数据表明，丹参酮 IIA 是一种有价值的治疗方法，可通过靶向 GSK3β 来改善 AKI 后的肾脏挽救。
Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β.
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影响因子：
7.2
作者：
Ahn, Young-Min;Kim, Su Kang;Lee, Byung-Cheol
通讯作者：
Lee, Byung-Cheol
影响因子：
3.7
作者：
Castoldi A;Braga TT;Correa-Costa M;Aguiar CF;Bassi ÊJ;Correa-Silva R;Elias RM;Salvador F;Moraes-Vieira PM;Cenedeze MA;Reis MA;Hiyane MI;Pacheco-Silva Á;Gonçalves GM;Saraiva Câmara NO
通讯作者：
Saraiva Câmara NO
影响因子：
19.6
作者：
Dong, X.;Swaminathan, S.;Griffin, M. D.
通讯作者：
Griffin, M. D.
影响因子：
5.6
作者：
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通讯作者：
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影响因子：
6.1
作者：
Jo, SK;Sung, SA;Kim, HK
通讯作者：
Kim, HK