The Nephroprotective Effect of Tauroursodeoxycholic Acid on Ischaemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress
The Nephroprotective Effect of Tauroursodeoxycholic Acid on Ischaemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress
复制标题
牛磺熊去氧胆酸通过抑制内质网应激对缺血/再灌注引起的急性肾损伤的肾保护作用
DOI：
10.1111/j.1742-7843.2011.00854.x
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Mei, Changlin
中科院分区：
文献类型：
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作者：
Gao, Xiang;Fu, Lili;Mei, Changlin
急性肾损伤（阿基）的发生率很高，涉及多种病理生理过程，包括内质网应激（ERS）。牛磺熊去氧胆酸（TUDCA）是一种内源性胆汁酸衍生物，据报道可抑制ERS。为了确定TUDCA是否对阿基具有肾保护作用并探讨确切机制，建立了缺血/再灌注（I/R）诱导的阿基小鼠模型和衣霉素预处理的TCMK-1细胞模型。结果发现，肾小管坏死评分和细胞凋亡指数在I/R后24小时达到峰值，与I/R后24小时相似。GRP 78和C/EBP同源蛋白（CHOP）表达和Caspase 12活化增强，分别在4和12小时达到峰值。TUDCA干预不仅降低肾小管坏死评分和细胞凋亡指数，而且下调GRP 78和CHOP表达和Caspase 12活化。经TUDCA预处理的TCMK-1细胞的存活率显著高于未经TUDCA预处理的TCMK-1细胞。总之，TUDCA通过抑制ERS、阻断GRP 78和CHOP表达、减少Caspase 12活化和抑制细胞凋亡对IR诱导的阿基具有肾保护作用。
The incidence of acute kidney injury (AKI) is very high, and multiple physiopathological processes are involved, including endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid derivative that has been reported to inhibit ERS. To determine whether TUDCA had a nephroprotective effect on AKI and to explore the exact mechanism, an ischaemia/reperfusion (I/R)-induced AKI mouse model and a tunicamycin-pre-treated TCMK-1 cell model were established. It was found that the renal tubular necrosis score and cell apoptosis index reached their peak 24 similar to hr after I/R. GRP78 and C/EBP homologous protein (CHOP) expression and Caspase 12 activation were enhanced, reaching their peaks at 4 and 12 similar to hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but also down-regulated GRP78 and CHOP expression and Caspase 12 activation. The survival rate of TCMK-1 cells pre-treated with TUDCA was significantly higher than that of TCMK-1 cells without TUDCA pre-treatment. In conclusion, TUDCA had a nephroprotective effect on IR-induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation and inhibiting cell apoptosis.