| ObjectiveTo observe the effect of blood glucose fluctuation on renal pathological change and collagen IV expression of diabetic rats.The male Sprague-Dawley (SD) rats were randomly assigned into normal group (NC) rats(n=20) and model group (DM) rats(n=55). Normal group rats were fed with normal diet, while diabetic model group rats were fed with high-sucrose-high-fat diet and after 4 weeks a low dose of streptozocin (STZ,35 mg/kg) was injected to induce diabetic model. And then the model group rats were divided randomly into two groups again:sustained high blood glucose group(n=21)and blood glucose fluctuation group(n=21).The latter group were induced by subcutaneous injecting insulin twice daily, while the other group were given equal dose physiological saline. We observed the survival rate, body weights, water intake, urine output, and detected the glucose level. All rats were executed after intervene 12 weeks, and collected the fasting blood and 24 hours urine before executed. The HbA1c, levels of lipid and renal functions were measured by the blood. The 24 hours protein uria were measured by the urine.Results1 The SD rats were successed induced into the diabetic models by fed with a high-sucrose-high-fat diet for four weeks and a low dose of STZ (35mg/Kg) was injected. The random glucose of all the diabetic model rats were more than 16.7mmol/L twice in different days. Compared with normal control group, the weights of diabetic group were increased. (p<0.05), while the insulin sensitive index was decreased (P<0.05)2 Compared with normal control group, survival rate and body weight were significantly lower, while water intake and urine output were obviously higher in sustained high blood group and blood glucose fluctuation group after the experiments over (p<0.05). There was no significant difference between sustained high blood group and blood glucose fluctuation one (P>0.05)3 Compared with normal control group, the average blood glucose levels(MBG), the standard deviation of daily average blood glucose (SDBG),the largest amplitude of glycemic excursions(LAGE) and the M-value were significantly increased in sustained high blood glucose group and blood glucose fluctuation group (p<0.05). Compared with sustained high glucose group, the MBG were significantly decreased in blood glucose fluctuation group, while the SDBG, LAGE, M-value were significantly increased (p<0.05). The blood glucose fluctuations could be induced by subcutaneous injecting insulin twice daily.4 Compared with normal control group, HbA1c were significantly higher in sustained high blood group and blood glucose fluctuation group (P<0.05),while there was no significant difference between the two diabetic groups. Compared with normal control group, TC, TG and LDL were significantly increased in sustained high blood group and blood glucose fluctuation group (p<0.05),while the level of HDL were decreased.But both of them were no significantly difference between high blood group and blood glucose fluctuation group (P>0.05)5 Compared with normal control group, the level of 24 hours proteinuria, BUN and SCr were significantly higher in sustained high blood group and blood glucose fluctuation group (p<0.01). Compared with sustained high blood group, the level of 24 hours proteinuria, BUN and SCr were significantly higher in blood glucose fluctuation group (p<0.05)6 Compared with normal control group, it could be seen that the renal glomeruli became larger, capillary basal membrane became thicker, capsular space extended, ground substance increased, the volume of renal tubule extended in the diabetic rats' kidney under the light microscope. The diabetic rats' kidney has come out the change of "high pressure, hypertransfusion, high filtration". Compared with sustained high glucose group, the pathological changes were more serious in the blood glucose fluctuation group, and the symptom of "three high" was more obvious.7 The normal control group rats' collagen IV immunohistochemical positive expression was mainly in membrane basement and mesenterium groundmass. The level of collagen IV was significantly increased in sustained high blood glucose group and blood glucose fluctuation group (P<0.01). Compared with sustained high blood glucose group, the level of Col IV was significantly increased in blood glucose fluctuation group(P<0.05).Conclusion1 The diabetic hyperglycemia circumstance could made the renal glomeruli larger, renal glomeruli capillary basal membrane thicker, ground substance increased, blood capillary broaden, permeability of renal glomeruli impaired, the renal tubule volume and lumina expanded. Compared with sustained high glucose group, the kidney's injury was more serious in blood glucose fluctuation group.2 The diabetic hyperglycemia circumstance could made the expression of rats'renal collagen IV increased, and the product of collagen IV was more in blood glucose fluctuation group than in sustained high glucose group, which could contribute to the development of diabetic nephropathy. |
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