ABSTRACT
BACKGROUND: Hepatic steatosis creates a significant risk of liver resection and transplantation and is extremely susceptible to ischemia/reperfusion (I/R) injury. Ischemic postconditioning (IPostC) has been shown to attenuate I/R injury in normal livers; however, its role in steatotic livers remains unknown. The current study sought to explore whether IPostC could attenuate normothermic I/R injury in rats with steatotic livers and to investigate potential protective measures. METHODS: Hepatic steatosis was triggered in Wistar rats fed high-fat diets. The role of IPostC was detected in normal and steatotic livers with 30 min of ischemia and 6 h of reperfusion. Blood and liver tissues were collected to assess hepatocyte damage, lipid peroxidation, inflammatory factors, neutrophil accumulation, and adenosine triphosphate (ATP) content. RESULTS: Compared to normal livers, steatotic livers were more susceptible to I/R damage, as evidenced by incremental concentrations of liver enzymes in the blood and more severe pathological changes in the liver. Hepatic I/R injury was significantly reduced by IPostC in both normal and steatotic livers. We further found that endogenous protective measures moderated lipid peroxidation, inflammatory cytokine expression and neutrophil accumulation, and reduced follow-up hepatic injury. The ATP content of steatotic livers was also significantly lower than that of Normal livers before and after I/R injury. IPostC greatly preserved the ATP content of normal and steatotic livers with I/R injury. CONCLUSIONS: IPostC appears to provide important protection against hepatic I/R injury in normal and steatotic livers under normothermic conditions. These data have important clinical implications for liver surgery and transplantation.
ABSTRACT
PURPOSE: The goal of this study is to evaluate the association between MMP-2, 3, TIMP-2, 3 polymorphisms and risk of colorectal cancer (CRC) in a Chinese Han population. METHODS: Eight single nucleotide polymorphisms (SNP) were genotyped in 505 CRC patients and 510 controls. The association between candidate SNPs and risk of CRC were evaluated using odds ratio (OR), 95% confidence interval (95% CI). RESULTS: The minor allele frequency of rs1053605 in cases was significantly lower than controls (p = 0.005). The CT genotype frequency of rs1053605 in cases was significantly lower than those in controls, while the frequencies of rs4789936-CT and rs715572-AG genotype of in cases were significantly higher than those in controls (p < 0.05). Genetic model analysis showed that rs522616 was associated with decreased risk of CRC under recessive model (p = 0.041); rs1053605 was correlated with decreased risk of CRC under dominant (p = 0.012) and additive (p = 0.009) models; rs4789936 also has association with decreased risk of CRC under recessive model (p = 0.021); while rs715572 was associated with increased risk of CRC under dominant (p = 0.007) and additive (p = 0.011) models. CONCLUSION: Our results shed new light on association between MMP and TIMP polymorphisms and CRC risk.
