幾種膳食多酚抑制STZ誘導(dǎo)大鼠糖尿病形成分子機(jī)制
本文選題:糖尿病大鼠 + 綠原酸; 參考:《湖南農(nóng)業(yè)大學(xué)》2012年碩士論文
【摘要】:研究目的:探討綠原酸、EGCG、槲皮素對STZ誘導(dǎo)的糖尿病大鼠的作用機(jī)制。并從中篩選出具有明顯抑制STZ(streptozocin)誘導(dǎo)大鼠形成糖尿病或改善大鼠糖尿病癥狀的膳食多酚。 研究方法:首先是對綠原酸干預(yù)糖尿病模型建立的觀察。本文采用高糖高脂加鏈脲佐菌素建立糖尿病大鼠模型,同時(shí)用綠原酸對其進(jìn)行干預(yù)。觀察綠原酸對糖尿病大鼠攝食量、飲水量、體重、生化指標(biāo)、肝臟G-6-pase和骨胳肌GLUT4mRNA表達(dá)的影響,并觀察腎臟和胰腺的形態(tài)學(xué)變化。然后比較綠原酸、EGCG、槲皮素對糖尿病大鼠的作用效果。在前一章研究的基礎(chǔ)上復(fù)制糖尿病大鼠模型。分別用二甲雙胍(陽性對照組)、綠原酸、EGCG和槲皮素治療糖尿病大鼠。從生物化學(xué)、分子生物學(xué)及病理學(xué)等多方向來檢測綠原酸、EGCG、槲皮素對糖尿病大鼠的作用,以此篩選出治療效果最好的膳食多酚。 研究結(jié)果:在綠原酸干預(yù)糖尿病大鼠中,本實(shí)驗(yàn)成功建立了糖尿病大鼠動(dòng)物模型。(1)與DM組相比,CA組攝食量(第8周和第9周)、飲水量(第9周)均顯著下降(P0.05),體重顯著升高(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組中的空腹血糖均顯著下降;口服葡萄糖0h和2h后,CA組血糖均顯著下降(P0.01)。(2)與DM組相比,CA組中FINS(P0.01)、HOMA-IR指數(shù)(P0.05)和腹控脂肪重(P0.01)顯著下降,TG、TC和LDL-C也均顯著下降(P0.01),ISI指數(shù)和HDL-C均顯著上升(P0.05)。(3)DM組肝臟中G-6-Pase mRNA表達(dá)顯著上升(P0.05)和骨胳肌GLUT4表達(dá)顯著下降(P0.05),但它們均因綠原酸干預(yù)而得到了一定的改善。(4)病理檢測觀察:DM組中腎小球肥大,遠(yuǎn)端、近端腎小管均出現(xiàn)空泡變性等病理改變;胰島細(xì)胞萎縮,形態(tài)不規(guī)則,細(xì)胞核不清晰,核質(zhì)顏色變淡等;β細(xì)胞表達(dá)非常少,而綠原酸則對上述情況均有所改善。 在綠原酸、EGCG、槲皮素對糖尿病大鼠療效的影響中,(1)與DM組相比,S組、CA組、Q組和E組較體重均上升,且S組、CA組的體重顯著提高(P0.01);口服葡萄糖試驗(yàn)中,血糖均下降,尤其Q組(0h,P0.05)和S組(0h,P0.01;2h,P0.05)顯著下降。(2)CA組和S組FINS、HOMA-IR指數(shù)均顯著下降(P0.01),Q組HOMA-IR指數(shù)也顯著下降(P0.01),CA組(P0.01)、S組(P0.05)和Q組(P0.05)ISI指數(shù)均顯著提高。TG、TC、LDL-C和FAA也均有不同程度的下降,但CA組的效果最好,接近于S組。(3)它們均抑制了肝臟G-6-pase mRNA的表達(dá),提高了骨胳肌GLUT4mRNA的表達(dá)。且其中以綠原酸效果最佳。但弱于陽性對照組二甲雙胍的作用。(4)與NC組相比,DM組中腎小球肥大,遠(yuǎn)端腎小管、近端腎小管均出現(xiàn)空泡樣變性等病理改變;胰島細(xì)胞也出現(xiàn)萎縮,形態(tài)不規(guī)則,界限不清楚,核質(zhì)顏色變淡等,β細(xì)胞表達(dá)也非常少,各藥物分別治療后,發(fā)現(xiàn)大鼠腎臟、胰腺形態(tài)學(xué)均有所改善,其中CA組形態(tài)學(xué)接近S組。但也并沒完全恢復(fù)到和NC組結(jié)構(gòu)一樣。 結(jié)論:綠原酸在干預(yù)糖尿病大鼠模型建立及改善糖尿病癥狀方面有顯著效果;且綠原酸、EGCG、槲皮素均能改善和減輕糖尿病大鼠癥狀,但綠原酸效果最好。
[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.
【學(xué)位授予單位】:湖南農(nóng)業(yè)大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2012
【分類號】:R587.1;R-332
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