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Serum-stabilized Naked Caspase-3 siRNA Protects Autotransplant Kidneys in a Porcine Model 期刊论文

编号：

34f85dec-5385-4783-99d2-976cdf45f93f
作者：

Yang, Cheng(杨橙)#^[1]Zhao, Tian(赵天)^[1]Zhao, Zitong(赵梓彤)^[1]Jia, Yichen(贾亦臣)^[1]Li, Long(李龙)^[1]Zhang, Yufang^[2];Song, Mangen^[1,3];Rong, Ruiming(戎瑞明)^[1,4]Xu, Ming(许明)^[1]Nicholson, Michael L.(李龙)^[5]Zhu, Tongyu(朱同玉)^[1,6]Yang, Bin^[1,2];
语种：

English
期刊：

MOLECULAR THERAPY ISSN：1525-0016 2014 年 22 卷 10 期 (1817 - 1828) ; OCT
收录：
摘要：

The naked small interfering RNA (siRNA) of caspase-3, a key player in ischemia reperfusion injury, was effective in cold preserved and hemoreperfused kidneys, but not autotransplanted kidneys in our porcine models. Here, chemically modified serum stabilized caspase-3 siRNAs were further evaluated. The left kidney was retrieved and infused by University of Wisconsin solution with/without 0.3 mg caspase-3 or negative siRNA into the renal artery for 24-hour cold storage (CS). After an intravenous injection of 0.9 mg siRNA and right-uninephrectomy, the left kidney was autotransplanted for 2 weeks. The effectiveness of caspase-3 siRNA was confirmed by caspase-3 knockdown in the post-CS and/or post-transplant kidneys with reduced apoptosis and inflammation, while the functional caspase-3 siRNA in vivo was proved by detected caspase-3 nnRNA degradation intermediates. HMGB1 protein was also decreased in the post-transplanted kidneys; correlated positively with renal IL-1 beta mRNA, but negatively with serum IL-10 or IL-4. The minimal off-target effects of caspase-3 siRNA were seen with favorable systemic responses. More importantly, renal function, associated with active caspase-3, HMGB1, apoptosis, inflammation, and tubulointerstitial damage, was improved by caspase-3 siRNA. Taken together, the 2-week autotransplanted kidneys were protected when caspase-3 siRNA administrated locally and systemically, which provides important evidence for future clinical trials.
推荐引用方式
GB/T 7714：

Yang Cheng,Zhao Tian,Zhao Zitong, et al. Serum-stabilized Naked Caspase-3 siRNA Protects Autotransplant Kidneys in a Porcine Model [J].MOLECULAR THERAPY,2014,22(10):1817-1828.
APA：

Yang Cheng,Zhao Tian,Zhao Zitong,Jia Yichen,&Yang Bin.(2014).Serum-stabilized Naked Caspase-3 siRNA Protects Autotransplant Kidneys in a Porcine Model .MOLECULAR THERAPY,22(10):1817-1828.
MLA：

Yang Cheng, et al. "Serum-stabilized Naked Caspase-3 siRNA Protects Autotransplant Kidneys in a Porcine Model" .MOLECULAR THERAPY 22,10(2014):1817-1828.

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