Study On Changes Of Mitochondrial DNA ATPase 6,8 Genes And Their Expressions Of Small Intestine Epithelial Cells In Hemorrhagic Shock Rats

The energy metabolism dysfunction takes place in hemorragic shock.It introduced cell injury,especially, the cells of small intestine. The small intestine serves as an important target organ in hemorragic shock and, its barrier damage plays an important role in the pathogenesis of irreversible shock and multiple system organ failure. Mitochondria is an organelle for energy transform.The mitochondria of higher mammal contains its own genome and biosynthetic institution.The mitochondrial DNA(mtDNA) ATPase6,8 genes (ATPase6,8 genes) coding for part F0 of F0F1-ATP synthase (ATPase) have a close relation to mitochondrial energy metabolism. Mitochondria is highly sensitive to ischemia and hypoxia. But it is still unclear whether ATPase6,8 genes and their expressions were changed. The present study was designed to explore the cause of mitochondrial energy metabolism dysfunction.The changes of ATPase6,8 genes and their expressions in a rat model of hemorrhagic shock were investgated.The main results and conclusions were as following:1. The small intestine epithelial cellular mtDNA ATPase6,8 genes sequences of 6 rats were examined in this study. The sequenced results were compared with rattus norvegicus(Wistar) mitochondrial genome in GeneBank. There was a A7797deletion mutation of ATPase8 gene in shock 5h group and its mutation was found in all hemorrhagic shock rats(n=3) and there was no mutation at the 7797 site in the control group. The c8294t,c8344t mutation occurred also.Their mutational rates were 1/3, respectively.2. The expression of ATPase6,8 genes increased in shock 1h, 2h. Then it decreased gradually. In hemorragic shock 5h group,it lowered markedly compared with control group (p<0.05). This result indicated that the decrease of ATPase6,8 mRNA may result in the mitochondrial dysfunction and irreversible shock.3. The mitochondrial respiratory control ratio(RCR) decreased continuously. In hemorrhagic shock 2h group and 5h group, the mean longpathway,surface density, volume density of mitochondrial profilean, mean profile area significantly increased compared with control group.Meanwhile the specific surface, numerial density decreased by 32%(p<0.01), 24%(p<0.05) respectively. The primary changes of mitochondrial morphometry were swelling and disorganization of cristal and matrix,while its quantity reduced in hemorrhagic shock. The results showed that changes of mitochondrial morphometry and function were strongly related to the changes of the gene and its expression.The results suggested that the mutation and abnormal expression of ATPase6,8 genes was a cause,or major contribtution factor in development of irreversible shock and dysfunction of mitochondrial energy metabolism of small intestinal epithelia.Decreasing the damage of mt DNA and preventing down -regulation of ATPase6,8 mRNA after the ischemia and hypoxia was important significance in the therapy of shock.