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首页> 外文期刊>Acta Pharmacologica Sinica >Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models
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Effects of specific interleukin-1β-converting enzyme inhibitor on ischemic acute renal failure in murine models

机译：特异性白介素-1β转化酶抑制剂对小鼠模型急性缺血性肾衰竭的影响

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Aim: To study the effect of selective interleukin-1β-converting enzyme (ICE, caspase-1) inhibitor on ischemic acute renal failure (ARF). Methods: Mouse models of ischemic ARF were treated with the specific ICE inhibitor AC-YVAD-CMK. A renal function assay and renal morphological studies were employed to estimate the renal protective effect of AC-YVAD-CMK. The survival rate of mouse models was also analyzed by a time series test. Furthermore, renal ICE activity, mature interleukin-18 (IL-18) protein expression and interferon-γ (IFN-γ) mRNA expression were also detected by fluorescent enzyme-linked immunosorbent assay (ELISA), ELISA, and semi-quantitative reverse transcription-polymerase chain reaction, respectively. Results: The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) increased remarkably in the model controls compared with the sham-operated groups (P < 0.01). Typical renal tubular necrosis was found in the model controls. Renal ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression were also increased significantly in the model controls compared with the sham-operated groups. The levels of BUN and Scr in the AC-YVAD-CMK therapy group were decreased significantly compared with the untreated model controls (P < 0.01). Renal tubulointerstitial lesion was also attenuated significantly (P < 0.05). AC-YVAD-CMK therapy alleviated the clinical features of ARF, and increased the survival rate (P < 0.01). Furthermore, AC-YVAD-CMK therapy also decreased ICE activity, mature IL-18 protein expression, and IFN-γ mRNA expression in renal tissue (P < 0.05). Conclusion: The selective ICE inhibitor AC-YVAD-CMK can effectively protect the kidney from acute ischemic lesions. This protective effect is associated with decreased renal ICE activity and suppressed IL-18 maturation and IFN-y mRNA transcription.
机译：目的：研究选择性白介素-1β转化酶（ICE，caspase-1）抑制剂对缺血性急性肾衰竭（ARF）的影响。方法：用特定的ICE抑制剂AC-YVAD-CMK治疗缺血性ARF的小鼠模型。通过肾功能测定和肾形态学研究来评估AC-YVAD-CMK的肾脏保护作用。还通过时间序列测试分析了小鼠模型的存活率。此外，还通过荧光酶联免疫吸附测定（ELISA），ELISA和半定量逆转录检测了肾脏的ICE活性，成熟的白介素18（IL-18）蛋白表达和干扰素-γ（IFN-γ）mRNA表达。 -聚合酶链反应。结果：与假手术组相比，模型对照组的血尿素氮（BUN）和血清肌酐（Scr）水平显着增加（P <0.01）。在模型对照中发现典型的肾小管坏死。与假手术组相比，模型对照组的肾脏ICE活性，成熟的IL-18蛋白表达和IFN-γmRNA表达也显着增加。与未治疗的模型对照组相比，AC-YVAD-CMK治疗组的BUN和Scr水平显着降低（P <0.01）。肾小管间质病变也明显减轻（P <0.05）。 AC-YVAD-CMK疗法减轻了ARF的临床特征，并提高了生存率（P <0.01）。此外，AC-YVAD-CMK治疗还降低了肾组织的ICE活性，成熟的IL-18蛋白表达和IFN-γmRNA表达（P <0.05）。结论：选择性ICE抑制剂AC-YVAD-CMK可有效保护肾脏免受急性缺血性损伤。这种保护作用与降低肾脏ICE活性和抑制IL-18成熟和IFN-γmRNA转录有关。

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