几种膳食多酚抑制STZ诱导大鼠糖尿病形成分子机制

发布时间：2018-06-28 22:39

本文选题：糖尿病大鼠 + 绿原酸　；参考：《湖南农业大学》2012年硕士论文

【摘要】：研究目的：探讨绿原酸、EGCG、槲皮素对STZ诱导的糖尿病大鼠的作用机制。并从中筛选出具有明显抑制STZ(streptozocin)诱导大鼠形成糖尿病或改善大鼠糖尿病症状的膳食多酚。研究方法：首先是对绿原酸干预糖尿病模型建立的观察。本文采用高糖高脂加链脲佐菌素建立糖尿病大鼠模型,同时用绿原酸对其进行干预。观察绿原酸对糖尿病大鼠摄食量、饮水量、体重、生化指标、肝脏G-6-pase和骨胳肌GLUT4mRNA表达的影响,并观察肾脏和胰腺的形态学变化。然后比较绿原酸、EGCG、槲皮素对糖尿病大鼠的作用效果。在前一章研究的基础上复制糖尿病大鼠模型。分别用二甲双胍(阳性对照组)、绿原酸、EGCG和槲皮素治疗糖尿病大鼠。从生物化学、分子生物学及病理学等多方向来检测绿原酸、EGCG、槲皮素对糖尿病大鼠的作用,以此筛选出治疗效果最好的膳食多酚。研究结果：在绿原酸干预糖尿病大鼠中,本实验成功建立了糖尿病大鼠动物模型。(1)与DM组相比,CA组摄食量(第8周和第9周)、饮水量(第9周)均显著下降(P0.05),体重显著升高(第8周(P0.05),第9周(P0.01))：注射STZ3天(P0.01)、10天(P0.05)和17天(P0.01)后,CA组中的空腹血糖均显著下降；口服葡萄糖0h和2h后,CA组血糖均显著下降(P0.01)。(2)与DM组相比,CA组中FINS(P0.01)、HOMA-IR指数(P0.05)和腹控脂肪重(P0.01)显著下降,TG、TC和LDL-C也均显著下降(P0.01),ISI指数和HDL-C均显著上升(P0.05)。(3)DM组肝脏中G-6-Pase mRNA表达显著上升(P0.05)和骨胳肌GLUT4表达显著下降(P0.05),但它们均因绿原酸干预而得到了一定的改善。(4)病理检测观察：DM组中肾小球肥大,远端、近端肾小管均出现空泡变性等病理改变；胰岛细胞萎缩,形态不规则,细胞核不清晰,核质颜色变淡等；β细胞表达非常少,而绿原酸则对上述情况均有所改善。在绿原酸、EGCG、槲皮素对糖尿病大鼠疗效的影响中,(1)与DM组相比,S组、CA组、Q组和E组较体重均上升,且S组、CA组的体重显著提高(P0.01)；口服葡萄糖试验中,血糖均下降,尤其Q组(0h,P0.05)和S组(0h,P0.01；2h,P0.05)显著下降。(2)CA组和S组FINS、HOMA-IR指数均显著下降(P0.01),Q组HOMA-IR指数也显著下降(P0.01),CA组(P0.01)、S组(P0.05)和Q组(P0.05)ISI指数均显著提高。TG、TC、LDL-C和FAA也均有不同程度的下降,但CA组的效果最好,接近于S组。(3)它们均抑制了肝脏G-6-pase mRNA的表达,提高了骨胳肌GLUT4mRNA的表达。且其中以绿原酸效果最佳。但弱于阳性对照组二甲双胍的作用。(4)与NC组相比,DM组中肾小球肥大,远端肾小管、近端肾小管均出现空泡样变性等病理改变；胰岛细胞也出现萎缩,形态不规则,界限不清楚,核质颜色变淡等,β细胞表达也非常少,各药物分别治疗后,发现大鼠肾脏、胰腺形态学均有所改善,其中CA组形态学接近S组。但也并没完全恢复到和NC组结构一样。结论：绿原酸在干预糖尿病大鼠模型建立及改善糖尿病症状方面有显著效果；且绿原酸、EGCG、槲皮素均能改善和减轻糖尿病大鼠症状,但绿原酸效果最好。
[Abstract]:Objective: To investigate the mechanism of chlorogenic acid, EGCG and quercetin on STZ induced diabetic rats, and to screen out the dietary polyphenols which can inhibit the formation of diabetes in rats or improve the symptoms of diabetic rats induced by STZ (streptozocin).
Study methods: first, the establishment of diabetic model by chlorogenic acid was established. In this paper, diabetic rat model was established by high glucose and streptozotocin, and chlorogenic acid was used to interfere with it. The intake of chlorogenic acid in diabetic rats, drinking water, weight, biochemical index, liver G-6-pase and skeletal muscle GLUT4mRNA expression were observed. Influence, and observe the morphological changes of the kidney and pancreas. Then compare the effects of chlorogenic acid, EGCG, quercetin on diabetic rats. On the basis of the previous chapter, the diabetic rat model was replicated. The diabetic rats were treated with metformin (positive control group), chlorogenic acid, EGCG and quercetin. Pathology and other directions to detect chlorogenic acid, EGCG, quercetin in diabetic rats, so as to screen out the best dietary polyphenols.
Results: in diabetic rats, diabetic rats were successfully established in this experiment. (1) compared with the DM group, the intake of diet (eighth weeks and ninth weeks), drinking water (ninth weeks) decreased significantly (P0.05), and the weight was significantly increased (eighth weeks (P0.05), ninth weeks (P0.01)): STZ3 days (P0.01), 10 days (P0.05) and 17 days (P0.01). After the oral glucose 0h and 2H, the blood glucose of group CA decreased significantly (P0.01). (2) compared with the DM group, FINS (P0.01), HOMA-IR index (P0.05) and abdominal fat weight (P0.01) decreased significantly in the CA group. 6-Pase mRNA expression significantly increased (P0.05) and skeletal muscle GLUT4 expression significantly decreased (P0.05), but they were improved by chlorogenic acid intervention. (4) pathological examination: pathological changes of glomerular hypertrophy in the DM group, distal, proximal renal tubules and other pathological changes, islet cell atrophy, irregular shape and unclear nucleus. The expression of cytoplasm was pale, and the expression of beta cells was very small, while chlorogenic acid improved the above conditions.
In the effect of chlorogenic acid, EGCG and quercetin on the effect of diabetic rats, (1) compared with group DM, group S, CA group, Q group and E group increased significantly, and the weight of CA group increased significantly in S group (P0.01), and in oral glucose test, blood glucose decreased significantly, especially in Q group (0h, P0.05) and CA group. The number of HOMA-IR decreased significantly (P0.01), and the HOMA-IR index in group Q was also significantly decreased (P0.01), CA group (P0.01), S group (P0.05) and Q group (P0.05) ISI index were significantly increased, but the results were best, close to the group. (3) they all inhibited the expression of liver and increased the table of skeletal muscle. The effect of chlorogenic acid was best, but the effect of metformin in the positive control group was weaker. (4) compared with the NC group, the glomerular hypertrophy, the distal renal tubules and the proximal renal tubules all had vacuolated degeneration in the DM group, and the islet cells also atrophied, irregular shape, unclear boundary, light nuclear color and so on, and the expression of beta cells was also expressed. Very few, after the treatment of each drug, it was found that the kidney of the rat was improved, and the morphology of the CA group was close to the S group, but it was not completely restored to the structure of the NC group.
Conclusion: chlorogenic acid has significant effect on the establishment of diabetic rat model and the improvement of diabetes symptoms, and chlorogenic acid, EGCG, quercetin can improve and alleviate the symptoms of diabetic rats, but the effect of chlorogenic acid is the best.
【学位授予单位】：湖南农业大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R587.1;R-332

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