【摘要】 目的 探讨卡维地洛在动脉粥样硬化病变中的抗氧化作用及其对增殖细胞核抗原（PCNA）及核因子kappaBp65（NFκBp65）活化的影响。方法 雄性新西兰大耳白兔24只，随机分为正常组、高脂组、卡维地洛组，每组8只，共计喂养10周。实验结束后，酶法检测各组家兔的血清三酰甘油及胆固醇，黄嘌呤氧化法检测血清超氧化物歧化酶（SOD），硫代巴比妥酸比色法检测丙二醛（MDA）,并采用免疫组化的方法测定血管壁PCNA及NFκBp65的表达。结果 高脂组和卡维地洛组血清三酰甘油和胆固醇较正常组明显升高（F=146.25、287.83,q=14.76～20.75,P<0.01），而该两组间差别无统计学意义（q=0.53、0.59,P>0.05）。高脂组较正常组SOD明显降低，MDA明显增加，而卡维地洛组较高脂组SOD有所升高，MDA有所降低（F=21.65、75.64,q=4.98～24.29,P<0.01）。高脂组PCNA和NFκBp65的表达较正常组明显增加，卡维地洛组PCNA和NFκBp65的表达较高脂组明显减少（F=426.12、521.38,q=56.15～75.87,P<0.01）。PCNA和NFκBp65的呈正相关（r=0.975，P<0.01）。结论 卡维地洛有减轻脂质过氧化损伤的作用，可阻断NFκB的活化，进而抑制平滑肌细胞的增殖。
【关键词】 动脉硬化 卡维地洛 抗氧化剂 细胞增殖 兔
［ABSTRACT］ObjectiveTo study the effect of carvedilol on antioxidation and activation of PCAN and NFκB on atherosclerosis.MethodsTwentyfour male New Zealand white rabbits were randomly divided into three groups: normal group, highfat diet group and cavediloltreated group, with eight rabbits in each group. All the rabbits were fed for 10 weeks. After completion of the experiment, the levels of serum triglyceride and cholesterol were measured by enzymatic method, of serum SOD by xanthine oxidative technique, and of serum MDA by thiobarbituric acid method. Expression of the PCAN and NFκBp65 in the vascular wall was detected immunohistochemically. ResultsCompared with those of normal rabbits, the levels of serum triglyceride and cholesterol of the highfat diet and cavediloltreated were extremely high （F=146.25，287.83； q=14.76-20.75； P<0.01), but no statistical difference was found between the latter two groups （q=0.53，0.59; P>0.05). Lowlevel serum SOD and highlevel serum MDA were noticed in highfat diet rabbits. In highfat diet group, SOD was lower than that in normal group, and MDA was higher; in cavediloltreated group, SOD was higher, and MDA was lower as compared with normal group （F=21.65，75.64; q=4.98-24.29; P<0.01）. The expression of PCNA and NFκBp65 in highfat diet group was markedly increased as compared with the normal group; but the expression was decreased in carvedilol group as compared with highfat diet （F=426.12，521.38; q=56.15-75.87； P<0.01）. An analysis showed that a positive correlation existed between PCNA and NFκBp65. Conclusion Carvedilol might relieve the lipid peroxidation injury and block NFκB activation so as to inhibit the proliferation of smooth muscle cells.
［KEY WORDS］ atherosclerosis; carvedilol; antioxidants; cell proliferation; rabbits
动脉粥样硬化(AS)是许多心脑血管疾病的基础性病理表现,也是中老年人常见疾病之一，严重威胁着人类的健康。氧化损伤是AS病变过程中核心环节，而平滑肌细胞的迁移增殖是斑块形成、管腔狭窄的直接原因。卡维地洛是具有多种药理活性的第三代β受体阻滞剂，除具有非选择性β受体阻滞作用外，还有α1受体阻断作用。近年来的研究表明，卡维地洛具有较强的抗氧化作用，这使其在抗AS病变中具有重要意义。本实验通过高脂饮食加免疫损伤内皮的方法诱发家兔AS模型，观察卡维地洛对AS病变过程中脂质过氧化损伤、增殖细胞核抗原（PCNA）及核因子kappaBp65（NFκBp65）表达的影响，进一步阐述其抗AS作用机制，从而为临床治疗AS提供依据。
卡维地洛抗动脉粥样硬化作用的研究
2025-04-29
卡维地洛抗动脉粥样硬化作用的研究.doc
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