Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys

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• 作者：Cheng Yang ; MD^a ; ^b ; ¹ ; Yichen Jia ; MD^a ; ^b ; ¹ ; Tian Zhao ; MD^a ; ^b ; ¹ ; Yinjia Xue ; MD^a ; ^b ; Zitong Zhao ; MD^a ; ^b ; Junlin Zhang ; MM^c ; Jina Wang ; MD ; PhD^a ; ^b ; Xuanchuan Wang ; MD^a ; ^b ; Yongyin Qiu ; MD^a ; ^b ; Miao Lin ; MD^a ; ^b ; Dong Zhu ; MD^a ; ^b ; Guisheng Qi ; MD ; PhD^a ; ^b ; Yue Qiu ; MM^a ; ^b ; Qunye Tang ; BS^a ; ^b ; Ruiming Rong ; MD ; PhD^a ; ^b ; Ming Xu ; MD ; PhD^a ; ^b ; Sujie Ni ; MM^d ; Bin Lai ; MM^d ; Michael L. Nicholson ; MD ; PhD^e ; ^{mln2@le.ac.uk} ; Tongyu Zhu ; MD ; PhD^a ; ^b ; ^{tyzhu@fudan.edu.cn} ; Bin Yang ; MD ; PhD^c ; ^e ; ^by5@le.ac.uk ; ^{dryangbin@hotmail.com}
• 关键词：Small interfering RNA ; Porcine kidney autotransplantation ; Ischemia&ndash ; reperfusion injury ; Caspase 3 ; Apoptosis ; Inflammation
• 刊名：Journal of Surgical Research
• 出版年：2013
• 出版时间：15 May, 2013
• 年：2013
• 卷：181
• 期：2
• 页码：342-354
• 全文大小：2497 K

文摘

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.