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目的:检测环氧合酶-2(COX-2)在兔主动脉粥样硬化(AS)中的表达及其与AS病变的相关性,观察血管紧张素Ⅱ受体阻断剂厄贝沙坦(irbesartan,Irb)对COX-2的影响,并与阳性对照剂塞来昔布(celecoxib,Cele)进行比较。方法:健康雄性新西兰兔30只随机分为5组。除对照组外,高胆固醇(HC)、小剂量(Sirb),大剂量(Lirb)和Cele组均喂养高胆固醇饮食,14周后取各组兔主动脉,行AS斑块面积及主动脉内膜/中膜比值测定,采用RT-PCR和免疫组化、Wester Blot法分别检测主动脉AS斑块中COX-2 mRNA和蛋白的表达。结果:Lirb和Cele组AS斑块面积均较HC组显著减小(P<0.01)。Lirb和Cele组内膜/中膜厚度较HC组明显减小(P<0.01)。HC组COX-2mRNA和蛋白的表达较对照组显著增强(P<0.01);Lirb和Cele干预后明显下降(P<0.01)。COX-2的表达与AS斑块面积显著正相关(P<0.01)。结论:COX-2与AS病变密切相关。厄贝沙坦可能在阻断AgII作用的同时抑制了AS中COX-2的表达,并且能达到塞来昔布抑制COX-2的程度,从而抗AS炎症。
Objective: To detect the expression of cyclooxygenase-2 (COX-2) in aortic atherosclerosis (AS) and its relationship with AS in rabbits. To observe the effects of angiotensin Ⅱ receptor blocker irbesartan (irbesartan, Irb) on COX-2 and compared with the positive control celecoxib (Cele). Methods: Thirty healthy male New Zealand rabbits were randomly divided into five groups. Except the control group, high cholesterol diet was given to high cholesterol (HC), low dose (Sirb), high dose (Lirb) and Cele groups. After 14 weeks, The ratio of membrane / mesothelial cells was determined by RT-PCR and immunohistochemistry. The expression of COX-2 mRNA and protein in AS plaques was detected by Wester Blot method. Results: The area of AS plaques in Lirb and Cele group was significantly lower than that in HC group (P <0.01). Intima / media thickness in Lirb and Cele group was significantly lower than that in HC group (P <0.01). The expression of COX-2 mRNA and protein in HC group was significantly higher than that in control group (P <0.01), but decreased significantly after Lirb and Cele treatment (P <0.01). COX-2 expression was positively correlated with AS plaque area (P <0.01). Conclusion: COX-2 is closely related to the pathological changes of AS. Irbesartan may inhibit the expression of COX-2 in AS while blocking the action of AgII, and it can reach the degree that COX-2 can be inhibited by celecoxib to prevent AS inflammation.