| Objective: Various studies have demonstrated that SAHS can lead to liver injury. Repetitive intermittent hypoxia, the hallmark feature of SAHS, leads to hepatic steatosis and nonalcoholic fatty liver disease. Inflammation is indispensable in the progress of NAFLD. Regulatory T cells(Treg) has been identified as an important role of the adaptive immune response in the pathogenesis of NASH, and it may participate the inflammation of NASH induced by chronic intermittent hypoxia. The mechanism of immune response Tregs involved in is still unknown.In this research, we imitate the chronic intermittent hypoxia process and induce NASH in Wistar rats to study how Tregs work in NAFLD induced by CIH, and explore the immune mechanism of Tregs in the progress.Methods: Dividing 32 male Wistar rats into 4 groups. Group A is control group, and the rats are fed with normal diet. Group B is intermittent hypoxia group, and the rats are treated with intermittent hypoxia. Group C is high-fat group, and the rats are fed with high fat food. Group D is high-fat and intermittent hypoxia group, and the rats are fed with high fat diet and are put in the air condition of intermittent hypoxia. After 4 weeks, we get their blood to check liver enzyme, MDA, blood lipid and proinflammatory cytokine. We make hepatic tissue and check histology of liver of all the rats. Check Foxp3 in liver by immunohistochemistry, and use Western Blot technology to detect Foxp3 and NF-κB protein in liver tissue.Results:(1) The influence of chronic intermittent hypoxia on liver structure: group B and C appeared to have hepatic steatosis. Intermittent hypoxia group began to appear steatohepatitis; hepatic steatosis in high-fat group was more serious. Group D had not only steatohepatitis but also hepatic fibrous hyperplasia. ALT, AST level in group D was much higher than group A, B, and C. Under light and electron microscopes, we can see the same results.(2) CIH and AST, ALT, inflammation indicator: compared with control group, ALT and AST level in group D is significantly higher. The serum malondialdehyde(MDA) level in B, C and D is significantly higher than control group. TNF-α in group B, C, and D are much higher than group A; IL1 in group D is significantly higher than others group; The hepatic tissue NF-κB protein expression in group D and group B was much higher than that of group A; Group D was significantly higher than group B; Group C and group A had no statistic difference.(3) Effect of CIH on Foxp3+ Tregs in liver: Foxp3 expression is significantly lower in group D than in other groups.Conclusion: This study shows that(1) Chronic intermittent hypoxia have an important influence on liver, especially with a high-fat diet;CIH can rise liver enzyme level and the feature of liver histology is the same as that of NASH.In the progress that simple fatty liver become steatohepatitis, CIH plays an important role.(2) In the process that liver injury making by CIH, there are oxidative stress reaction and liver inflammation.(3) Foxp3 expressed by Tregs is significantly lower in group D than in other group, which means Treg have an effect of protecting liver from in inflammation caused by SAHS in NASH. Our research put one step further in inflammation mechanism of liver injury making by CIH and giving basic support for those who looking for new treatments of this condition. |
