Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys
Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys
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裸Caspase 3小干扰RNA在猪肾冷保存中有效，但在自体移植中无效
DOI：
10.1016/j.jss.2012.07.015
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发表时间：
2013-05-15
影响因子：
2.2
通讯作者：
Yang, Bin
中科院分区：
文献类型：
--
作者：
Yang, Cheng;Jia, Yichen;Yang, Bin
背景：Caspase 3与细胞凋亡和炎症反应相关，在缺血再灌注损伤中起重要作用。裸caspase 3小干扰RNA（siRNA）的有效性已在离体猪肾灌注模型中得到证实，但在自体transplantation.Materials和Methods：从小型猪中取出左肾，将含有或不含0.3 mg caspase 3 siRNA的威斯康星州大学溶液注入肾动脉，夹闭肾动脉和静脉，冷藏24 h。右肾切除后，将左肾自体移植到右肾48 h，不进行siRNA全身治疗。结果：荧光染料标记的caspase 3 siRNA在CS后肾中可见，但在移植后减弱。siRNA可下调CS后肾脏caspase 3 mRNA及其前体的表达。然而，在siRNA保存的移植后肾脏中，caspase 3信使RNA和活性亚基上调，前体细胞进一步减少，但活性caspase 3+细胞、凋亡细胞和髓过氧化物酶+细胞增加。结论：裸caspase 3 siRNA对移植肾的冷保存效果显著，但对移植肾的保护作用不明显，可能是由于系统性互补反应克服了局部效应。(C)2013 Elsevier Inc. All rights reserved.
Background: Caspase 3 associated with apoptosis and inflammation plays a key role in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not in autotransplantation.Materials and methods: The left kidney was retrieved from mini pigs and infused with the University of Wisconsin solution with or without 0.3 mg of caspase 3 siRNA into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was autotransplanted into the right for 48 h without systemic treatment of siRNA.Results: Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS kidneys but was weakened after transplantation. The expression of caspase 3 messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA and active subunit were upregulated with further decreased precursor but increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells. Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal function was not significantly changed.Conclusions: Naked caspase 3 siRNA administered into the kidney was effective in cold preservation but not enough to protect posttransplant kidneys, which might be because of systemic complementary responses overcoming local effects. (C) 2013 Elsevier Inc. All rights reserved.