| Objective: Diabetes (DM) is a kind of metabolic syndrome caused by theinsulin secretion or function defects，in which continous high blood glucose isthe main feature. Long-term metabolic disturbance of carbohydrates, fats andprotein can cause multi-system damage, resulting in chronic degenerativedeseases of organs such as eyes, kidneys, nerves, heart and blood vessels. Thetype2diabetes (T2DM) accounts for over90%of all diabetes. Currently, theetiology and pathogenesis of T2DM has not fully understood, and the effectivetreatment is needed.Chronic intermittent hypobaric hypoxia (CIHH) has a variety ofbeneficial effects on the body, such as cardioprotetive effects by enchancingthe resistance of heart against myocardial ischemia/reperfusion injury andcardiac antiarrhythmic, anti-hypertension in renal vascular hypertension in ratscaused by2K1C, and protective effect of collagen-induced rheumatoidarthritis. Some reseaches demonstrated that CIHH can improve glucose andlipid metabolism. The reseach of CIHH on type2diabetes, however, is less,and the effect of CIHH on type2diabetes has not determined. This study wasdesigned to explore the effect of CIHH on lipid metabolism in type2diabeticrats induced by high-fat combined with low dose streptozotocin (STZ) dietand ivvestigate effect of CIHH.Methods: Adult male SD rats were randomly divided into four groups:diabetic group (DM), chronic intermittent hypobaric hypoxia group (CIHH),diabetes plus CIHH treatment group (DM+CIHH) and control group (CON).DM rats received a low-dose streptozotocin intraperitoneal injection (30mg/kg)to induce type2diabetes after four weeks of high-fat diet; CIHH rats weregiven CIHH simulating5000m altitude for28days,6hours a day; DM+CIHHrats accept both DM and CIHH treatment; CON rats do not accept anytreatment. Artery blood pressure, body weight, food intake, water intake and urine output in all rats were recorded at the same time each week. Bloodserum triglyceride (TG), total cholesterol (CHO), low-density lipoproteincholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), free fattyacids (NEFA) and insulin (INS) in rats were measured in the fifth and thenineth weeks, respectively. Rats were given50%glucose intraperitonealinjection (2g/kg) for glucose tolerance test and insulin (1U/kg) for insulintolerance test. After rats sacrificed at the9th week of experiment, thephosphoenolpyruvate carboxylase (PEPCK) expression in liver tissue wasassayed with western blotting method, and histological changes of liver wasobserved with HE staining.Results:1There was no significant difference of body weight, food intake,water intake and urine output between CON and CIHH rats, and betweenDM+CIHH and DM rats (P>0.05); The food intake, water intake and urineoutput were increased， but body weight was decreased in DM ratssignificantly compared with CON rats (P<0.05).2Compared with CON rats, the blood pressure in DM rats wasincreased significantly (P<0.01); the blood pressure in DM+CIHH rats wassignificantly lower than that in DM rats (P<0.01); the blood pressure CIHHrats was higher than CON rats only at sixth week (P<0.05), and no significantdifference during other times between both groups (P>0.05).3Compared with CON rats, the area under the glucose tolerance curve(AUC) in DM rats was significantly higher (P<0.01); the area in DM+CIHHrats was significantly lower than that in DM rats (P<0.01); there was nosignificant difference of the aera between both groups (P>0.05).4During insulin tolerance testing, glucose level was lower at0-minutein CIHH rat than in CON rats (P<0.05), and no difference of glucose level atother time points between both groups (P>0.05); glucose level was lower at60-minutes and120-minute in DM+CIHH rats than DM rats (P<0.05), and nodifference of glucose level at0-minute between DM+CIHH and DM rats(P>0.05). 5Blood TG, TC and INS in DM+CIHH rat were lower than those inDM rats (P<0.01); there was no significant difference of TG, TC and INSbetween CON and CIHH rats (P>0.05).6Insulin sensitivity index (ISI) was lower in DM+CIHH rat than that inDM rats (P<0.01); there was no difference of ISI between CON and CIHHrats (P>0.05).7The result of HE staining showed that great amont of fat dropletswere found in liver of DM rats, a small amont of fat droplets were found inDM+CIHH rats, and no fat droplets was observed in CON and CIHH rats.8PEPCK expression in liver was lower in DM+CIHH rats than that inDM rats (P<0.05); there was no significant difference of liver PEPCKexpression between CIHH and CON rats (P>0.05).Conclusion: CIHH has a significant protective effect against type2diabetic rats induced by high-energy high-fat diet combined with low doses ofSTZ, improving dyslipidemia and abnormal glucose tolerance, and decreasingabnormal high blood pressure in diabetic rats. This protective effect of CIHHis related with the improvement of insulin resistance and the decrease ofPEPCK expression of liver. |
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