Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion
Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion
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DOI：
10.1111/aor.12607
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发表时间：
2016-06-01
影响因子：
2.4
通讯作者：
Ye, Qifa
中科院分区：
文献类型：
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作者：
Zhong, Zibiao;Hu, Qianchao;Ye, Qifa
低温机器灌注（MP）可减轻肾移植术后移植物损伤；然而，其机制尚未阐明。近十年来，许多研究表明乙醛脱氢酶2（ALDH2）是一种能够抑制细胞凋亡的蛋白酶。因此，本研究旨在探讨ALDH2是否参与减轻MP后的器官损伤。 18只健康雄性新西兰兔（12周龄，体重3.0±0.3kg）随机分为三组：正常组、MP组和冷藏（CS）组（n=6）。夹闭左肾蒂使家兔左肾热缺血35min，再灌注1h。左肾采用MP或CS（4℃，4h）在体保存，右肾切除，24h再灌注，然后采集标本和血液。最后检测尿肌酐（Cr）、血尿素氮（BUN）和4-HNE浓度。 TUNEL染色检测肾细胞凋亡，免疫组化或Western blot检测肾组织中ALDH2、cleaved-caspase 3、bcl-2/bax、MAPK的表达情况；术后24h MP组Cr浓度为355±71mol/L，CS组Cr浓度为511±44mol/L（P
Hypothermic machine perfusion (MP) can reduce graft's injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 +/- 0.3kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n=6). The left kidney of rabbits underwent warm ischemia for 35min through clamping the left renal pedicle and then reperfusion for 1h. Left kidneys were preserved by MP or CS (4 degrees C for 4h) in vivo followed by the right nephrectomy and 24-h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4-HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved-caspase 3, bcl-2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24h after surgery, the concentration of Cr in MP group was 355 +/- 71mol/L, in CS group was 511 +/- 44mol/L (P