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目的本实验通过高脂饮食建立早期高脂血症兔模型,观察普罗布考对胆固醇相关转运体以及炎症因子的影响。方法新西兰白兔36只,雄雌不拘,采用数字表法随机分为基础组(n=9)、基础+普罗布考组(每只77 mg/d,n=9)、高脂组(n=9)和高脂+普罗布考组(每只77 mg/d,n=9)。40天后观察普罗布考对血脂的影响;HE染色观察普罗布考对各组新西兰白兔腹主动脉斑块形成的影响;油红O染色观察普罗布考对各组新西兰白兔肝脏脂质蓄积的影响;定量PCR测定普罗布考对新西兰白兔腹主动脉、肝脏和小肠中胆固醇相关转运体基因表达的影响;Western blot以及免疫组化测定普罗布考对新西兰白兔腹主动脉、肝脏、小肠内胆固醇相关转运蛋白表达的影响;ELISA方法测定普罗布考对炎症因子的影响。结果与基础组相比,高脂组免血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)水平均明显升高;与高脂组比较,高脂+普罗布考组免血清TC、LDL-C、HDL-C、TG水平均明显下降;高脂组中有动脉斑块形成,肝脏脂质蓄积增多;高脂+普罗布考组中,普罗布考明显抑制斑块的形成,减少肝脏脂质蓄积;普罗布考促进肝脏中ABCG1和SR-BI蛋白及其mRNA的表达,抑制ABCA1蛋白及其mRNA的表达,对SR-A和CD36的表达没有影响;普罗布考抑制炎症因子如IL-6、MCP-1、MCSF、VCAM-1、TNF-α的表达。结论普罗布考抑制ABCA1和炎症因子的表达,促进ABCG1和SR-B1的表达。
Objective To establish an early hyperlipidemic rabbit model by high-fat diet and observe the effects of probucol on cholesterol-related transporters and inflammatory cytokines. Methods Thirty-six New Zealand white rabbits were randomly divided into basic group (n = 9), probucol group (77 mg / d, n = 9 each) = 9) and high fat + probucol group (77 mg / d each, n = 9). 40 days later, the effect of probucol on blood lipid was observed; the effect of probucol on the formation of abdominal aorta plaque in New Zealand white rabbits was observed by HE staining; the effect of probucol on lipid accumulation in liver of New Zealand white rabbits Western blot and immunohistochemistry were used to determine the effect of probucol on the gene expression of cholesterol-related transporter in the abdominal aorta, liver and small intestine of New Zealand white rabbits. Small intestine cholesterol-related transporter protein expression; ELISA method probucol probed the impact of inflammatory cytokines. Results Compared with the basal group, the levels of serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) Compared with the high-fat group, the levels of serum TC, LDL-C, HDL-C and TG were significantly decreased in the high fat + probucol group and in the high fat group with arterial plaque formation and hepatic lipid accumulation; In probucol + probucol group, probucol significantly inhibited plaque formation and decreased hepatic lipid accumulation. Probucol promoted the expression of ABCG1 and SR-BI proteins and their mRNA in the liver and inhibited the expression of ABCA1 protein and its mRNA , And had no effect on the expression of SR-A and CD36; probucol suppressed the expression of inflammatory factors such as IL-6, MCP-1, MCSF, VCAM-1 and TNF-α. Conclusion Probucol inhibits the expression of ABCA1 and inflammatory cytokines and promotes the expression of ABCG1 and SR-B1.