The Expression And Roles Of Peroxisome Proliferators-activated Receptors, NF-κB And SOD In The Liver Of Obstructive Jaundice In Rats

Objective: Obstructive jaundice is a syndrome that bile excretion disorders due to various reasons, cholestasis in liver destroys the normal biliary tract, and lead to organs damage. Obstructive jaundice leads severe damage to human organs, such as multiple organ disfunction syndrom and multiple organ failure (MOF).The molecule mechanisms of this damage of obstructive jaundice have been becoming the study focus. Previous studies suggested that oxidative stress probably plays an important role in liver injury induced by obstructive jaundice. Superoxide dismutase (SOD), a potent antioxidant enzyme, has been shown to minimize a variety of oxidative injuries in vitro and in vivo. SOD genes significantly reduced hepatocyte injury immersion in serum of OJ rat, contrarily, TNF-αsignificantly increased. Acording to this result, we assume whether a upstream key regulatory factor regulate the expression of SOD and TNF-α, and to be a novel gene target in protective treatment of the liver damage in obstructive jaundice.Peroxisome proliferator–activated receptors (PPARs) are members of the ligand-activated nuclear hormone receptor superfamily which firstly found by Issemann and Green in 1990, and play key roles in the regulation of adipocyte differentiation, lipometabolism, inflammation, resistance of lipid-peroxidation. Nuclear factor-κB (NF-κB) is an important transcription regulatory factor of proinflamatory, plays a key role in inflammatory and oxidative stress. In the present study, to determine expression of PPARs, SOD and NF-κB in rats liver induced by bile duct ligation, and elucidate the molecule regulate mechanisms of hepatic injury of obstructive jaundice, and find the novel treatment.Methods: One hundred twenty male SD rats were randomly divided into four groups: sham operated seven days group and bile duct ligation (BDL) seven days group,sham operated nineteen days group and BDL nineteen days group. All rats were sacrificed on 7th day and 19th day after BDL and obtained blood samples and liver tissue. Total bilirubin(TB), direct bilirubin(DB), alanine aminotransferase (ALT) in serum were detected and liver tissue HE pathology section were evaluated. SOD enzyme activity was detected by SOD kit. Reverse Transcription-PCR was performed to obtain the mRNA expression information of PPARs in all groups rats liver, and standardized by theβ-actin. The detection of PPARs protein and activation of NF-κB were performed using a immunohistochemistry method.Results: In our study, we observed that in BDL animals serum TB, DB and ALT were significantly increased compared with the sham group (P<0.01). By HE pathology section, we observed that in the BDL group liver occured significant damage signs, and the change on 19th day after BDL were more obviously. The activity of normal SOD and CuZn-SOD were decreased as compared with the sham group (P<0.01), and the decent on 19th day after BDL were more significantly. The level of PPARs expression in the BDL groups liver except the PPARβin the BDL 7th group were reduced as compared with the sham group (P<0.01), and the level 19th day after BDL were more significantly. From immunohistochemistry, we observed that PPARs protein expression were significantly inhibited (P<0.01), in sham group, nearly no positive expression was observed in liver, but in BDL group NF-κBp65 activation and nuclear displacement response, on 19th day after BDL were more significantly. we observed that SOD in BDL groups,liver were significant positive correlation as compared with PPARs protein expression (P<0.01), but NF-κBp65 protein expression were significant negative correlation as compared with PPARs protein expression (P<0.01).Conclusion: In this study, we found that PPARs were inhibited on expression level, and more significantly as the pathological process extent. PPARs might be a key regulatory factor for SOD and NF-κB. The low expression of PPARs down-regulated expression of SOD by weaken the positive regulation of SOD, and reduced the negative regulation of NF-κB in liver of obstructive jaundice rats, lead to lipid peroxidation damage and that inflammation was out of control. That might be the important molecule mechanism in liver damage of obstructive jaundice.