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| Effects of ALDH2 on mitochondrial stress during ischemia-reperfusion in rats |
| Wang Yi-qun, Yao Ping-bo, Zhao Hong |
| Department of Anesthesiology， Affiliated Nanhua Hospital, Nanhua University, Hengyang 421002, China |
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Abstract Objective To explore the effect of acetaldehyde dehydrogenase-2 (ALDH2) on mitochondrial stress after the injury of intestinal ischemia/reperfusion (I/R). Methods Thirty-two male Sprague-Dawley rats were randomly divided into pseudo-surgical group, I/R model group, ALDH2-siRNA group and Srambled-siRNA group. And each group had eight rats. Rat model of intestinal I/R injury was established by ligation the superior mesenteric artery blood flow for 1 h and reperfusion for 2 h. However, no ligation was performed in the pseudo-surgical group. ALDH2-siRNA group was injected ALDH2-siRNA 1 ml in preoperative 24, 6, 1 hour by tail vein. And scrambled-siRNA group was injected scrambled-siRNA. However, pseudo-surgical group and I/R model group were injected with the same amount of sodium chloride injection. After 2 h reperfusion, blood was taken and intestinal tissue was sacrificed. The contents of interleukin (IL-6) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected by ELISA. The levels of ALDH2 and mitochondrial stress related factors, such as heat shock protein (HSP60, HSP70), NIP3 protein (Nix) and mRNA expression in intestinal tissues were detected by Western blot and reverse-transcription PCR (RT-PCR). Results Compared with the pseudo-surgical group, the levels of inflammatory cytokines were significantly increased in the I/R model group ［IL-6 (ng/L): 172.6±38.7 vs. 450.3±101.8, P＜0.01; TRAF6 (ng/L): 499.5±142.1 vs. 962.5±213.8, P＜0.01］. And the protein levels of mitochondrial stress factors were significantly increased in the I/R model group (HSP60: 1.00±0.15 vs.4.19±0.38, P＜0.01; HSP70: 1.00±0.12 vs.3.22±0.41, P＜0.01; Nix: 1.00±0.12 vs.3.03±0.31, P＜0.01). In addition, mRNA levels of mitochondrial stress factors were significantly increased in the I/R model group (HSP60: 1.00±0.23 vs.11.16±0.40, P＜0.01; HSP70: 1.00±0.14 vs.5.13±0.61, P＜0.01; Nix: 1.00±0.11 vs.8.41±0.52, P＜0.01). While the expression of ALDH2 was low. Compared with the I/R model group, the levels of serum inflammatory factors were significantly increased in the ALDH2-siRNA group ［IL-6 (ng/L): 450.3±101.8 vs.613.3±134.5, P＜0.05; TRAF6 (ng/L): 962.5±213.8 vs.1383.4±238.3, P＜0.01］. And the protein levels of mitochondrial stress factors were significantly increased in the ALDH2-siRNA group (HSP60: 4.19±0.38 vs.6.02±0.51, P＜0.01; HSP70: 3.22±0.41 vs.5.11±0.52, P＜0.01; Nix: 3.03±0.31 vs,4.48±0.50, P＜0.01). Moreover, their mRNA levels were significantly increased in the ALDH2-siRNA group (HSP60: 11.16±0.40 vs.14.87±0.58, P＜0.01; HSP70: 5.13±0.61 vs.7.17±0.65, P＜0.01; Nix: 8.41±0.52 vs.9.97±0.78, P＜0.01). However, the level of ALDH2 was significantly decreased. Conclusion ALDH2 may mediate inflammation and mitochondrial stress signaling pathway to inhibit inflammation and regulate the homeostasis of mitochondrial stress so as to protect the intestinal I/R injury of rats.
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Corresponding Authors:
Zhao Hong, E-mail: zhaohong779900@163.com
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