Molecular Mechanism Of Dietary Polyphenols Inhibit Rat Developing To Diabetic Induced By STZ

Objective:To discusse the mechanism of chlorogenic acid, EGCG and quercetin on diabetic rat indued by streptozocin, and screen the dietary polyphenol with the obvious inhibiting diabetic rat by streptozocin or improving symptoms of diabetic rat.Methods:The intervention of chlorogenic acid on diabetic model was observed.. This paper established diabetic rat model by high fat and sugar combined with streptozotocin, intervened with chlorogenic acid at the same time. The effects of chlorogenic acid on food intake, water intake, body weight, biochemical indexes, G-6-pase mRNA expression in liver and GLUT4mRNA expression in skeletal muscle of diabetic rats were observed, and the morphological changes of kidney and pancreas were also observed. Then the effects of chlorogenic acid, EGCG and quercetin on diabetic rats were compared. Based on the study of the previous chapter, diabetic rat model was replicated and treated with metformin (positive control group), chlorogenic acid, EGCG and quercetin respectively. The effects of chlorogenic acid, EGCG and quercetin on diabetic rats were detected in multiple directions of biochemistry, molecular biology and pathology, to screen dietary polyphenol with the best efficacy.Results:In the experiment of chlorogenic acid intervention on diabetic rats, diabetic rat model was successfully established.(1) Compared with DM group, feed intake (the eighth and ninth weeks), water intake (the ninth week) of CA group decreased significantly (P<0.05), and body weight (the eighth week (P<0.05), the ninth week (P<0.01)) increased significantly; after STZ injection for3days (P<0.01),10days (P<0.05) and17days (P<0.01), the fasting blood glucose of CA group significantly decreased; at0and2hours after taking oral glucose, blood glucose of CA group decreased significantly (P<0.01).(2) Compared with DM group, FINS (P<0.01), HOMA-IR (P<0.05) and abdominal fat weight (P<0.01) of CA group decreased significantly, and TG, TC and LDL-C significantly decreased (P<0.01), while ISI and HDL-C significantly increased (P<0.05).(3) Liver G-6-Pase mRNA expression of DM group increased significantly (P<0.05) and skeletal muscle GLUT4expression decreased significantly (P<0.05), but chlorogenic acid intervention got definite improvement.(4) Pathological detection showed that:in DM group, there were glomerular hypertrophy, vacuolar degeneration and other pathological changes in distal and proximal renal tubules; and for islet cells there were atrophy, irregular shape, unclear nucleus and nucleoplasm with lighter color; β cells expressed very little, whereas these situations were improved by chlorogenic acid.In the experiment comparing the effects of chlorogenic acid, EGCG and quercetin on diabetic rats,(1) compared with DM group, the body weights of S group, CA group, Q group and E group increased, and the body weights of S group and CA group increased significantly (P<0.01); In oral glucose tolerance test, blood glucose of the above groups decreased, especially of Q group (Oh, P<0.05) and S group (Oh, P<0.01;2h, P<0.05) decreased significantly.(2) FINS and HOMA-IR of CA group and S group decreased significantly (P<0.01), and HOMA-IR of Q group decreased significantly (P<0.01), while ISI of CA group (P<0.01), S group (P<0.05) and Q group (P<0.05) were significantly improved. TG, TC, LDL-C and FAA also declined to different extents, but CA group had the best improvement, close to S group.(3) All of them inhibited G-6-pase mRNA expression in liver and improved GLUT4mRNA expression in skeletal muscle, of which chlorogenic acid had the best effect, but weaker than the effect of metformin in positive control group.(4) Compared with NC group, DM group had glomerular hypertrophy, vacuolar degeneration and other pathological changes in renal distal tubule and proximal renal tubule; islet cells had atrophy, irregular shape, unclear boundaries and nucleoplasm with lighter color and β cell expressed very little. After the treatment with these drugs, the morphology of kidney and pancreas in rats was improved, of which the morphology of CA group was close to that of S group, but not completely recovered to that of NC group.Conclusion:Chlorogenic acid have significant effect on intervention on diabetic rat model and improving the symptoms of diabetes; and chlorogenic acid, EGCG and quercetin can improve and alleviate the symptoms of diabetic rats, but chlorogenic acid has the best effect.