Small interfering RNA targeting TNFα gene signifi

Authors: Ling Hou Gang Chen Biao Feng Xusheng Zhang Xiufen Zheng Ying Xiang Guangyuan Zhao WeiPing Min

Publish Date: 2016/10/18

Volume: 36, Issue: 5, Pages: 634-638

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Abstract

Tumor necrosis factoralpha TNFα has been found to be centrally involved in the development of ischemiareperfusion injury IRIinduced inflammation and apoptosis Knockdown of TNFα gene using small interfering RNA siRNA may protect renal IRI Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min TNFα siRNA was administered intravenously to silence the expression of TNFα The therapeutic effects of siRNA were evaluated in terms of renal function histological examination and overall survival following lethal IRI A single systemic injection of TNFα siRNA resulted in significant knockdown of TNFα expression in ischemiareperfusion injured kidney In comparison with control mice levels of BUN and serum creatinine were significantly reduced in mice treated with siRNA Pathological examination demonstrated that tissue damage caused by IRI was markedly reduced as a result of TNFα siRNA treatment Furthermore survival experiments showed that nearly 90 of control mice died from lethal IRI whereas more than 50 of siRNApretreated mice survived until the end of the eightday observation period We have demonstrated for the first time that silencing TNFα by specific siRNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia highlighting the potential for siRNAbased clinical therapy

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