Abstract:Aim To explore the influence of high-cholesterol to islet beta cell and intervention effect of atorvastatin. Methods Twenty-four New Zealand white rabbits were randomly divided into control group, cholesterol group and atorvastatin group, with eight rabbits in each group. After feeding for six weeks, the empty stomach blood were collected for inspected fasting blood- glucose (FBG), insulin (FINS), total cholesterol (TC), low density lipoprotein cholesterol (LDLC) and triglyceride(TG) The oral glucose tolerance test (OGTT) were examined The pancreatic tissue was taken to observe islet morphology and insulin positive cells by immunohistochemical method,to detect proinsulin mRNA expression by RT-PCR, to measure oxidative stress index: malondialdehyde (MDA) and reducing glutathione (GSH) by spectrophotometry. Results In cholesterol group after sugar load of 30 and 60 min, the blood glucose, the date of aera-under-curve(AUC) and the insulin resistance index (HOMA-IR) was increased (P<0.05), and insulin sensitive index (ISI), beta cell function index (HBCI/IR) was lower than control group (P<0.05) A great deal of beta cell hypertrophy and arrangement disorder were observed in the cholesterol group,in addition,insulin positive expression was increased The proinsulin mRNA was over-active(P<0.05) MDA absorbance value was higher than that of the control group (P<0.05), and GSH absorbance value was just the opposite (P<0.05). In atorvastatin group insulin positive expression decreased compared with high cholesterol group, MDA absorbance value was lower (P<0.05), and GSH absorbance value was just the reverse (P<0.05). Then, fasting gloucose, blood glucose after sugar load of 120 min, HOMA-IR, HBCI/IR, ISI and proinsulin mRNA express had no significant difference. Conclusions Hypercholesterolemia may induce pancreas oxidation-antioxidation system imbalance, finally lead to islet beta cell morphology and function damage. Atorvastatin can significantly reduce pancreatic tissue oxidative stress, but can not improve the sugar metabolic disorders induced by high cholesterol.