特异性环氧化酶抑制剂对大鼠慢性压力负荷性心肌肥厚的影响  

Experimental study of selective cyclooxygenase-2 inhibitor on rats with pressure overloaded hypertrophic myocardium

作　　者：梁子敬[1] 曾量波[1] 叶政[1] 陈国勤[1] 王鹏鲲[1] 卢敏俊[1] 

机构地区：[1]广州医学院第一附属医院急诊科,广州510120

出　　处：《广东医学》2008年第5期743-745,共3页Guangdong Medical Journal

基　　金：广东省自然科学基金资助项目(编号:06022688)

摘　　要：目的观察特异性环氧化酶抑制剂对大鼠慢性压力负荷性心肌肥厚过程中左室重构的影响以及此过程中炎症反应标记物的动态变化。方法将SD大鼠随机分3组:模型对照组、模型组和实验组,模型组和实验组按腹主动脉缩窄致压力负荷性心肌肥厚制作大鼠模型。实验组加用特异性环氧化酶抑制剂(rofecoxib)干预,20周用高频超声测定左心室结构和功能,心肌组织胶原Masson染色,测定总胶原容积百分比(CVF-T)和无冠状动脉小血管视野胶原容积百分比(CVF-NV),检测大鼠不同时间炎症反应标记物的变化。结果模型组左室壁增厚,特别是室间隔增厚明显,左室重量增加(P<0.01),左室腔扩大。实验组左室舒张内径(LVDD)及左室重叠(LVM)较模型组降低(P<0.01)。模型组CVF-T和CVF-NV明显增加(P<0.001),实验组则减少(P<0.001),与模型对照组差异无显著性(P>0.05)。模型组TNF-α,IL-10升高(P<0.05),实验组均下降(分别P<0.05,P<0.01)。实验组TGF-β明显降低(P<0.01)。结论炎症参与了压力负荷性心肌肥厚过程,特异性环氧化酶抑制剂有抗心室重构作用,可能与通过抗炎症作用达到抗心肌纤维化作用有关。Objective To investigate the change of inflammation marker and the influence of selective cyclooxygenase - 2 inhibitor on rats with pressure overloaded hypertrophic myocardium. Methods SD rats were randomly divided into 3 groups： sham operated group, operated group and rofecoxib group. Hypertrophic myocardium was induced by gradually constricting the abdominal aorta in rats. Sixteen weeks later, rofecoxib group was treated with rofecoxib, a selective COX -2 inhibitor（20 mg·kg^-1·d^-1）in drinking water for 4 weeks. All rats were subjected to echocardiography to determine the left ventricular （LV） structures and functions at 20 weeks after operation. Hearts were analyzed for organ weight. Myocardial collagen was stained with Masson and CVF - T and CVF - NV were analyzed using a computer assisted procedure. Serum levels ofTNF - α, IL -6,IL - 10, TGF - β and CRP uric acid were measured at 7,12 and 20 weeks after operation respectively. Results Operated rats had increased LV wall thickness,LV internal diameter, LV mass and had reduced FS%, LVDD and LVM in rofecoxib group compared with operated group. CVF - T and CVF - NV was the greatest in operated group and there was difference between rofecoxib group and sham operated group. In comparison to sham operated group,TNF - α and IL - 10 in operated group increased at 20 weeks after operation, but treatment group decreased at 20 weeks. TGF - β in the treatment group was significantly lower than those of sham operated group and operated group. Conclusion Inflammatin was involved in the development of myocardial hypertrophy. Selective COX - 2 inhibitor may prevent myocardial fibrosis in pressure overload model.

关 键 词：特异性环氧化酶抑制剂 心肌肥厚 左室重构 炎症因子 

分 类 号：R977.3[医药卫生—药品] R972[医药卫生—药学]