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炎癥與氧化應(yīng)激在大鼠動脈粥樣硬化中的作用及藥物干預(yù)研究

發(fā)布時(shí)間:2018-06-16 18:16

  本文選題:炎癥 + 氧化; 參考:《青島大學(xué)》2014年碩士論文


【摘要】:目的:探討相關(guān)炎癥指標(biāo)與氧化應(yīng)激指標(biāo)在大鼠早期動脈粥樣硬化中的表達(dá)及應(yīng)用瑞舒伐他汀(Rosuvastatin)、普羅布考(Probucol)干預(yù)后對各項(xiàng)指標(biāo)的影響,并對兩藥作用進(jìn)行比較。 方法:雄性Wistar大鼠54只隨機(jī)分5組,正常飲食對照組(A組)12只,高脂飲食模型組(B組)12只、瑞舒伐他汀干預(yù)組(C組)10只、普羅布考干預(yù)組(D組)10只、瑞舒伐他汀+普羅布考干預(yù)組(E組)10只。正常飲食對照組給予普通飼料喂養(yǎng),高脂飲食模型組及藥物干預(yù)組給予高脂飼料喂養(yǎng)同時(shí)給予卵清白蛋白(2.5mg/kg)腹腔注射(5次/周)。C、D、E組從第9周開始,進(jìn)行藥物干預(yù)。第16周末,所有大鼠稱重,麻醉大鼠,開胸經(jīng)右心房取血,檢測血清血管內(nèi)皮細(xì)胞鈣黏蛋白(VE-cadherin)、脂聯(lián)素(APN)、8-異前列腺素-F2a(8-iso-PGF2a)、超氧化物歧化酶(SOD)表達(dá)。在光鏡下觀察大鼠主動脈病理組織學(xué)改變。 結(jié)果:與A組比較,模型組和藥物干預(yù)組體重明顯下降(P0.01),血清VE-cadherin、8-iso-PGF2a水平顯著升高(P0.01),APN、 SOD水平降低(p0.01);與B組比較,C、D、E組體重升高(P0.05)血清VE-cadherin、8-iso-PGF2a水平明顯降低(p0.01), APN、SOD表達(dá)升高(P0.05),血管內(nèi)膜損傷明顯減輕;與C組比較,D、E組血清8-iso-PGF2a水平下降(P0.01),SOD水平升高(P0.01);與C組比較,E組血清VE-cadherin降低(P0.01),APN升高(P0.01);與D組比較,E組血清VE-cadherin降低(P0.05),APN升高(P0.05);與CD組比較,E組血管內(nèi)膜變薄(P0.05)。結(jié)論:瑞舒伐他汀與普羅布考均具有抗炎和抗氧化作用,普羅布考的抗氧化作用優(yōu)于瑞舒伐他汀,兩藥聯(lián)合使用可明顯降低血清VE-cadherin、8-iso-PGF2a的水平,升高APN、SOD的表達(dá),并可減輕血管內(nèi)膜的病理改變。本實(shí)驗(yàn)可指導(dǎo)臨床用藥,在應(yīng)用瑞舒伐他汀基礎(chǔ)上加用普羅布考,可增強(qiáng)對血管內(nèi)膜的保護(hù)作用。
[Abstract]:Aim: to investigate the expression of inflammatory and oxidative stress indexes in early atherosclerosis of rats and the effects of rosuvastatin (Rosuvastatin) and probucol (Probucoll) on these indexes and compare the effects of the two drugs. Methods: Fifty-four male Wistar rats were randomly divided into 5 groups: normal diet control group (n = 12), high fat diet group (n = 12), control group (n = 10), rosuvastatin group (n = 10) and probucol group (n = 10). Rosuvastatin probucol intervention group (n = 10). The normal diet control group was fed with normal diet, the high fat diet model group and the drug intervention group were given high fat diet and ovalbumin 2.5 mg / kg). At the end of the 16th week, all the rats were weighed and anesthetized, and the blood was taken from the right atrium through the right atrium. The expression of VE-cadherin, adiponectin (APN) 8-iso-PGF2aI, and superoxide dismutase (SOD) were detected. The histopathological changes of rat aorta were observed under light microscope. Results: compared with group A, body weight in model group and drug intervention group decreased significantly (P 0.01), serum VE-cadherinine 8-iso-PGF2a level increased significantly (P 0.01) and SOD level decreased (P 0.01). Compared with group B, the serum VE-cadherinine 8-iso-PGF2a level was significantly decreased, the expression of APN- SOD increased and the vascular intima injury was alleviated, compared with group C, the serum 8-iso-PGF2a level decreased, and the serum VE-cadherin decreased P0.01APN increased P0.01a, compared with C group, the serum VE-cadherin decreased P0.01APN increased P0.01a. Compared with group D, the serum VE-cadherin in E group decreased the level of P0.05APN increased, and that in group E was thinner than that in group CD. Conclusion: both rosuvastatin and probucol have anti-inflammatory and anti-oxidation effects. The antioxidant effect of probucol is better than that of rosuvastatin. The combined use of the two drugs can significantly reduce the level of serum VE-cadherinine 8-iso-PGF2a and increase the expression of APN- SOD. And can alleviate the pathological changes of vascular intima. This experiment can be used to guide the clinical use of Risuvastatin plus Probucol, which can enhance the protective effect on vascular intima.
【學(xué)位授予單位】:青島大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R543.5

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