Bcl-2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis
Bcl-2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis
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DOI：
10.3727/000000008783907053
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Imai, Enyu
中科院分区：
文献类型：
--
作者：
Suzuki, Chigure;Isaka, Yoshitaka;Imai, Enyu
缺血再灌注导致严重的器官损伤和功能障碍。炎症反应被认为是缺血性肾移植中移植肾功能障碍的最重要原因。缺血后引发炎症和肾损伤的机制仍有待阐明;然而，细胞应激可能在移植后的最初几小时和几天内诱导细胞凋亡，这可能在早期移植物功能障碍中起关键作用。已知Bcl-2抑制由促进缺血和再灌注损伤的病因学因素诱导的细胞凋亡。因此，我们推测抗凋亡因子Bcl-2的增加可能通过抑制凋亡来保护肾小管上皮细胞，从而改善随后的肾小管间质损伤。我们使用Bcl-2转基因小鼠（Bcl-2 TG）及其野生型同窝小鼠（WT）研究Bcl-2过表达对缺血再灌注（I/R）损伤的影响。阻断左肾动、静脉45 min，再灌注0-96 h，观察肾缺血再灌注损伤的影响。Bcl-2 TG组肾小管细胞caspase活性降低，TUNEL阳性凋亡细胞减少。因此，Bcl-2 TG中的间质纤维化和表型改变得到改善。总之，Bcl-2增强通过抑制肾小管细胞凋亡保护肾小管上皮细胞免受I/R和随后的间质损伤。
Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucidated; however, cellular stress may induce apoptosis during the first hours and days after transplantation, which might play a crucial role in early graft dysfunction. Bcl-2 is known to inhibit apoptosis induced by the etiological factors promoting ischemia and reperfusion injury. Accordingly, we hypothesized that an augmentation of the antiapoptotic factor Bcl-2 may thus protect tubular epithelial cells by inhibiting apoptosis, thereby ameliorating the subsequent tubulointerstitial injury. We examined the effects of Bcl-2 overexpression on ischemia-reperfusion (I/R) injury using Bcl-2 transgenic mice (Bcl-2 TG) and their wild-type littermates (WT). To investigate the effects of I/R injury, the left renal artery and vein were clamped for 45 min, followed by reperfusion for 0-96 h. Bcl-2 TG exhibited decreased active caspase protein in the tubular cells, which led to a reduction in TUNEL-positive apoptotic cells. Consequently, interstitial fibrosis and phenotypic changes were ameliorated in Bcl-2 TG. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R, and subsequent interstitial injury by inhibiting tubular apoptosis.