MECHANISM OF ALDOSE REDUCTASE MEDIATED INTESTINAL MUCOSAL INJURY IN ACUTE HYPOXIC YOUNG RATS BY REGULATING MITOCHONDRIAL FUNCTION

Danhe Shi¹, Xia Guo¹, Caiwen Yan¹, Fang Xiang², Shaofeng Wang^{1, *}

¹Changzhi People's Hospital, Changzhi, PR China - ²Peace Hospital Affiliated to Changzhi Medical College, Changzhi, PR China

Objective: To explore the mechanism of aldose reductase mediated intestinal mucosal injury in acute hypoxic young rats by regulating mitochondrial function. 

Methods: Thirty SD rats were randomly divided into sham operation group, model group and eparltast group, with 10 rats in each group. Intestinal ischemia-reperfusion models were established in both model group and AR inhibitor group. Epalrestat group was injected 10mg/kg epalrestat intravenously 10 minutes before modeling. In the sham operation group, only the superior mesenteric artery was exposed and isolated and sutured. He staining was used to detect the pathological changes of small intestine tissues of rats in each group, and the degree of injury was evaluated according to Aurelie Le mandat Schultz pathological score. The expression levels of Bcl-2, Bax mRNA and protein in small intestine tissues of rats in each group were detected by fluorescence quantitative PCR and Western blot. The contents of lactic acid and MDA in rat mucosal tissue were detected by spectrophotometer, the level of MPO was detected by colorimetry, the apoptosis rate was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and the mitochondrial transmembrane potential of intestinal mucosal cells was detected. 

Results: the pathological scores of rats in the model group and eparltast group were significantly higher than those in the sham operation group (P<0.05); The pathological score of rats in eparltast group was significantly higher than that in model group (P<0.05). Lactic acid, MDA and MPO in mucosal tissue of rats in model group and eparltast group were significantly higher than those in sham operation group (P<0.05); Lactic acid, MDA and MPO in mucosal tissue of rats in eparltast group were significantly higher than those in model group (P<0.05). The apoptosis rate of mucosal tissue in model group and eparltast group was significantly higher than that in sham operation group (P<0.05); The apoptosis rate of mucosal tissue in eparltast group was significantly higher than that in model group (P<0.05). The Bcl-2 mRNA and protein in the mucosa of rats in the model group and eparltast group were significantly lower than those in the sham operation group (P<0.05); Bcl-2 mRNA and protein in mucosal tissue of rats in eparltast group were significantly lower than those in model group (P<0.05). Bax mRNA and protein in mucosal tissue of rats in model group and eparltast group were significantly higher than those in sham operation group (P<0.05); Bax mRNA and protein in mucosal tissue of rats in eparltast group were significantly higher than those in model group (P<0.05). The mitochondrial membrane potential of rat mucosal tissue cells in the model group and eparltast group were significantly lower than that in the sham operation group (P<0.05); The mitochondrial membrane potential of mucosal tissue cells in eparltast group was significantly lower than that in model group (P<0.05). 

Conclusion: aldose reductase plays a role in mediating intestinal mucosal injury in young rats with acute hypoxia, and its mechanism may be achieved by regulating mitochondrial function.