本文關(guān)鍵詞： 北五味子醇提物 動(dòng)脈粥樣硬化 氧化應(yīng)激 內(nèi)皮 蛋白表達(dá)　出處：《西南交通大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的對(duì)北五味子醇提物抗動(dòng)脈粥樣硬化的作用進(jìn)行研究,并探討其作用機(jī)制。方法采用腹腔注射VD3+高脂飼料喂養(yǎng)9周建立大鼠動(dòng)脈粥樣硬化模型,以辛伐他汀作為陽(yáng)性對(duì)照(4mg/kg/d),灌胃北五味子低(0.35g/kg/d)、中(0.7g/kg/d)、高(1.4 g/kg/d)劑量醇提物3周。雙試劑直接法測(cè)定大鼠血清中甘油三酯(TG)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)的含量,微板法測(cè)定血清中谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)的活性,對(duì)肝組織、主動(dòng)脈進(jìn)行蘇木精-伊紅(HE)染色,觀察各組大鼠肝臟以及主動(dòng)脈的病理改變。生化法檢測(cè)大鼠血清中谷胱甘肽-過氧化物酶(GSH-PX)、過氧化氫酶(CAT)、超氧化物歧化酶(SOD)的活性以及丙二醛(MDA)的含量;利用免疫組織化學(xué)法檢測(cè)大鼠主動(dòng)脈核因子相關(guān)因子-2(Nrf-2)、血紅素氧合酶(HO-1)蛋白的表達(dá)情況,采用酶聯(lián)免疫吸附(ELISA)法檢測(cè)血清中氧化低密度脂蛋白(ox-LDL)、內(nèi)皮素-1(ET-1)、血栓素B2(TXB2)、6-酮-前列腺素F1α(6-keto-PGF1α)的表達(dá)情況,以說明北五味子醇提物治療動(dòng)脈粥樣硬化的作用機(jī)制。結(jié)果大鼠動(dòng)脈粥樣硬化模型成功建立,模型組大鼠主動(dòng)脈可見明顯的斑塊形成,血管壁內(nèi)膜增厚,斑塊內(nèi)可見數(shù)量不等的泡沫細(xì)胞。與模型組對(duì)比,北五味子醇提物各組的主動(dòng)脈可見內(nèi)膜、中膜和外膜,結(jié)構(gòu)相對(duì)完整,斑塊形成不明顯,血管內(nèi)膜增厚,平滑肌纖維病變較輕,可非常顯著降低AS模型大鼠主動(dòng)脈斑塊面積占血管壁面積的百分比(P0.01或P0.001),還可顯著降低主動(dòng)脈斑塊中的泡沫細(xì)胞數(shù)量(P0.05或P0.01)。肝組織病理觀察結(jié)果顯示,模型組肝臟中肝細(xì)胞胞漿內(nèi)可見較多大小不一的空泡,高劑量組與模型對(duì)照組相比胞質(zhì)內(nèi)未見明顯空泡且無(wú)病變。辛伐他汀組及北五味子醇提物各劑量組與模型對(duì)照組比較,能極顯著降低大鼠血清中TG的含量(P0.001),顯著性降低LDL-C的含量(P0.001或P0.01或P0.05),中、高劑量組可顯著性升高HDL-C的含量(P0.01或P0.05);辛伐他汀組及北五味子醇提物各組可顯著性降低大鼠血清ALT、AST的活性(P0.001或P0.01或P0.05)。北五味子醇提物組各組能顯著增強(qiáng)血清GSH-PX的活性,極顯著性降低血清中MDA的含量(P0.001),低、中劑量組可極顯著性增強(qiáng)CAT的活性(P0.001),低劑量組可顯著增強(qiáng)SOD的活性(P0.01);進(jìn)一步的作用機(jī)制研究結(jié)果顯示,北五味子醇提物各組均能極顯著性上調(diào)大鼠主動(dòng)脈Nrf-2的蛋白表達(dá)(P0.001),高劑量組能顯著性上調(diào)HO-1的蛋白表達(dá)(P0.01)。北五味子醇提物各組均能顯著降低ox-LDL的表達(dá)(P0.01),極顯著性上調(diào)6-keto-PGF1α的表達(dá)(P0.001),低、中劑量組可顯著降低ET-1的表達(dá)(P0.01或P0.05),而各劑量組對(duì)TXB2的表達(dá)無(wú)顯著影響。結(jié)論北五味子醇提物具有明顯的抗動(dòng)脈粥樣硬化作用,可促進(jìn)大鼠血脂代謝,其機(jī)制可能與激活Nrf-2/ARE通路,抑制ox-LDL、ET-1的蛋白表達(dá),調(diào)控血漿中TXB2和6-keto-PGF1α的平衡,調(diào)節(jié)機(jī)體氧化應(yīng)激水平并維持內(nèi)皮細(xì)胞功能有關(guān)。
[Abstract]:The purpose of anti atherosclerosis extract of Fructus schisandrae chinensis alcohol and the role of research, and to explore its mechanism. Methods for 9 weeks to establish the rat model of atherosclerosis by intraperitoneal injection of VD3+ high fat diet with simvastatin as positive control (4mg/kg/d), intragastric administration of five kinds of North Zi Di (0.35g/kg/d), in (0.7g/kg/d), high (1.4 g/kg/d) dose of ethanol extract for 3 weeks. Determination of triglycerides in serum of rats with double reagent direct method (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) content, micro plate method for the determination of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity of liver tissue and aorta were stained with hematoxylin eosin (HE) staining, observe the change of liver and aortic pathology. Glutathione peroxidase were detected in rat serum (GSH-PX), catalase (CAT), superoxide dismutase (SOD) activity and C Two aldehyde (MDA) content; detection of nuclear factor of aortic related factors in rats using immunohistochemical method, -2 (Nrf-2), heme oxygenase (HO-1) expression, by enzyme-linked immunosorbent assay (ELISA) method for the detection of oxidized low density lipoprotein in serum (ox-LDL), endothelin -1 (ET-1), thromboxane B2 (TXB2), 6- keto prostaglandin F1 alpha (6-keto-PGF1 alpha) expression, to illustrate the mechanism of alcohol extract of Schisandra chinensis on treating atherosclerosis. The rat model of atherosclerosis was successfully established, the rats in the model group showed obvious aortic plaque, intimal thickening of the vessel wall, ranging from the number of visible foam cells the plaque. Compared with the model group, the aortic intimal Schisandra alcohol extract group, middle and outer membranes, a relatively complete structure, plaque formation is not obvious, intimal thickening, smooth muscle fibers and mild lesions can be reduced significantly The AS model of rat aortic plaque area percentage of vascular wall area (P0.01 or P0.001), but also can significantly reduce the number of aortic plaque in foam cells (P0.05 or P0.01). Liver pathological observation showed that there were lots of vacuoles in the size of the liver in the model group liver cells, the high dose group and the model control group in the cytoplasmic vacuoles and no obvious lesions. Simvastatin group and ethanol extract of Schisandra chinensis in each dose group compared with the control group, could significantly reduce the content of serum TG (P0.001), significantly decreased the content of LDL-C (P0.001 or P0.01 or P0.05), and high dose group content increased significantly HDL-C (P0.01 or P0.05); simvastatin group and ethanol extracts of Schisandra chinensis group can significantly decrease the serum ALT of rats, the activity of AST (P0.001 or P0.01 or P0.05). The alcohol extract of Schisandra chinensis group can significantly enhance the serum The activity of GSH-PX significantly decreased the content of MDA in serum (P0.001), low dose group can significantly enhance the activity of CAT (P0.001), low dose group can significantly enhance the activity of SOD (P0.01); the mechanism study further showed that the expression of alcohol extract of Schisandra chinensis in each group significant upregulation of rat aortic Nrf-2 protein expression (P0.001), high dose group could significantly upregulate HO-1 protein (P0.01). The alcohol extract of Schisandra chinensis significantly reduced the expression of ox-LDL (P0.01), significantly up-regulated the expression of 6-keto-PGF1 alpha (P0.001), low dose group can significantly reduce the expression of ET-1 (P0.01 or P0.05), and the expression of each dose group of TXB2 had no significant effect. Conclusion Schisandra alcohol extract has obvious anti atherogenic effects can promote lipid metabolism in rats, and its mechanism may be related to the activation of the Nrf-2/ARE pathway, inhibition of ox-LDL, ET-1. White expression regulates the balance of TXB2 and 6-keto-PGF1 alpha in plasma, regulates the level of oxidative stress and maintains the function of endothelial cells.

【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R285.5

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