| Objective: Diabetes vascular complication is the major cause of mortality in the diabetic patients. Endothelial dysfunction is a common pathological phenomenon for diabetes vascular complication. Hyperglycemia is a symbol of diabetes and also a cause of diabetic vascular complication. The main ideas of the unifying mechanism of the development of diabetic complications are related to oxidative stress. The findings in the present research is that free radial reactions in the patients with DM were pathologically exacerbated, and the balance between oxidation and anti oxidation system are markedly disturbed, then lead to the damage of endothelial cells and accelerates the development of diabetic vascular complications. The phenomenon of clinical research show us that oxidative stress has been shown to be increased in the postprandial period in patients with diabetes and has been implicated in the pathogenesis of micro-and macrovascular complications. Normally, the level of blood glucose changes within a limited range. However, the inter and intra day glucose variability is relatively high in diabetic patients.Accumulating evidence indicates that besides glucohemoglobinAlc( HbAlc), glucose variability is an independent predictor of diabetic cardiovascular complications, the long-term fluctuated blood sugar does more damages than high blood sugar only.Basic and clinical reserches at home or aboard have paid great attention to blood glucose fluctuation and its damage impact on DM and its vascular complications, but the unifying mechanism of fluctuated blood sugar is not clear. The findings on aboard suggest that fluctuated glucose could be more deleterious to endothelial cells than constant high glucose group,relating to severely oxidative stress. These observations suggest that control of glucose excursions, and accompanying oxidative stress, during the postprandial period maybe important in the prevention of potential long-term diabetes complications. This paper is aiming to compare the effects of fluctuated glucose and constant high glucose media on the production of the factor of oxidative stress maleic dialdehyde (MDA) and glutathione (GSH), super oxide dismutase (SOD) in cultured human umbilical vein endothelial cells(HUVECs) line in vitro so as to explore the pathological effects of fluctuated glucose on diabetes vascular complication.Methods: The test simulate blood glucose fluctuation in diabetic patient.After 24 hour cultured in common DMEM medium without serum, Human umbilical vein endothelial cells cultured in vivo were grown to DMEM medium with 5% fetal bovine serum: normal control group contains glucose 5.5mmol/L; constant high glucose contains 25 mmol/L glucose; 5.5 mmol/L alternating with 25 mmol/L was fluctuated glucose group. They were exposed to experimental conditions for 72 hour. Culture medium was renewed 8 hour till 72 hour. The content of MDA were measured by thiobarbiturates. The production or activities of GSH, SOD were measured by UV-Spectrometer .Results:(1) After HUVECs were exposed to constant high glucose (25mmol/L) and fluctuated glucose (5.55/25 mmol/L) for 72h, the production of MDA had significantly increased compared with cells exposed to normal glucose, 6.54±0.35μmol/L (P< 0.001), 7.63±0.42μmol/L(P<0.001) respectively. Furthermore there was a significantly increase of MDA in fluctuated glucose compared with it in constant high glucose (P<0.001).(2) The impact of glucose fluctuation to the activities of SOD: the activities of SOD were lower significantly than normal glucose group that both in constant high glucose (25 mmol/L) and fluctuated glucose group(5.55/25 mmol/L), after HUVECs were exposed for 72h, 33.66±1.71 U/ml(P<0.05), 28.57±2.75 U/ml(P<0.01) respectively. Furthermore there was a significantly decrease of in fluctuated glucose the activities of SOD compared with it in constant high glucose(P<0.01).(3) In cultured HUVECs, exposed to constant high glucose (25 mmol/L) and fluctuated glucose (5.55/25 mmol/L) for 72h, the level of GSH were decreased significantly. Compared with cells exposed to normal glucose, the content of GSH were decreased to 86.43±2.79mg/L (P<0.01) , 78.47±2.77mg/L (P <0.001) respectively. Furthermore there was a significantly decrease of the level of GSH in fluctuated glucose compared with it in constant high glucose (P<0.001).Conclusion: The fluctuated glucose group had increased MDA compared with constant glucose group. However, both the production of GSH and the activity of SOD in fluctuated glucose group were significantly lower than those in constant high glucose group. Our data suggest that glucose fluctuation may be involved in the damage of endothelial cells. Based on the above results, it is found that fluctuated glucose do more harm to HUVECs cultuled in vivo compared with constant high glucose. The phenomenon are likely to caused by oxidative stress, then increases the vascular endothelial damage caused by oxidative stress in diabetes and accelerates the development of diabetic chronic vascular complications.
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