RESUMO
[ ABSTRACT] AIM:To explore the mechanisms of fluctuant high blood glucose-induced apoptosis of hepatocytes. METHODS:SD rats were randomly divided into normal control group ( N) , stable high blood glucose group ( S) , fluctu-ant high blood glucose group ( F) and insulin group ( I) .Diabetic rats were induced by intraperitoneal injection of strepto-zotocin (65 mg/kg) , and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time points every day.The blood glucose fluctuation patterns of the animals in F group with-in 12 weeks were similar every day and no significant difference of the HbA1c concentration was observed compared with S group, indicating that the fluctuant hyperglycemia was successfully established in F group.The activity of superoxide dis-mutase ( SOD) and glutathione peroxidase ( GSH-Px) , and the content of malondialdehyde ( MDA) and nitric oxide ( NO) in the homogenate of the liver tissues were detected by colorimetry.The mRNA and protein levels of JNK, p-JNK, Bax and Bcl-2 were examined by RT-PCR and Western blot.RESULTS:After 12 weeks, the increases in the intakes of food and water, the urine output, and the abnormal liver function were observed in S group, I group and F group.Compared with N group, the MDA level was increased, the content of NO and the activity of SOD and GSH-Px were decreased, and up-regu-lation of JNK mRNA and p-JNK and Bax proteins, and down-regulation of Bcl-2 were also found in S group, I group and F group.The above effects were more obviously showed in F group.CONCLUSION:Oxidative stress activates JNK-MAPK signaling pathway, which is involved in fluctuant high glucose-induced apoptosis of hepatocytes.