NLRP3 Inflammasome Involvement in the Organ Damage and Impaired Spermatogenesis Induced by Testicular Ischemia and Reperfusion in Mice

NLRP3 Inflammasome Involvement in the Organ Damage and Impaired Spermatogenesis Induced by Testicular Ischemia and Reperfusion in Mice
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DOI:
10.1124/jpet.115.226936
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发表时间:
2015-12-01
影响因子:
3.5
通讯作者:
Altavilla, Domenica
Altavilla, Domenica
中科院分区:
医学2区
文献类型:
--
作者:
Minutoli, Letteria;Antonuccio, Pietro;Altavilla, Domenica

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我们研究了核苷酸结合寡聚化结构域(NOD)样受体家族pyrin domain containing 3(NLRP 3)炎性小体在野生型(WT)和NLRP 3基因敲除(KO)小鼠睾丸缺血再灌注损伤(TI/R)中的作用。WT和KO小鼠经历1小时睾丸缺血,随后4小时和1天和7天再灌注或假TI/R。此外,两组WT小鼠在再灌注开始时用两种炎性体抑制剂BAY 11-7082(20 mg/kg i. p.)或亮蓝G(45.5mg/kg i. p.),或车辆。在4小时、第1天和第7天用过量戊巴比妥钠处死动物,并进行双侧扁桃体切除术。对各组进行生化和形态学研究。TI/R组再灌注4 h后caspase-1和IL-1 β mRNA表达显著增加,再灌注1d时IL-18 mRNA表达显著增加(P
We investigated the role of the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome during testis ischemia and reperfusion injury (TI/R) inwild-type (WT) and NLRP3 knock-out (KO) mice. WT and KO mice underwent 1 hour testicular ischemia followed by 4 hours and 1 and 7 days of reperfusion or a sham TI/R. Furthermore, two groups of WT mice were treated at the beginning of reperfusion and up to 7 days with two inflammasome inhibitors, BAY 11-7082 (20 mg/kg i.p.) or Brilliant Blue G (45.5 mg/kg i.p.), or vehicle. Animals were killed with a pentobarbital sodium overdose at 4 hours and 1 and 7 days, and bilateral orchidectomies were performed. Biochemical andmorphologic studies were carried out in all groups. TI/R in WT mice significantly increased caspase-1 and interleukin (IL)-1 beta mRNA after 4 hours and IL-18 mRNA at 1 day of reperfusion (P