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背景:细胞间黏附分子1作为炎症反应的可靠标志物在动脉粥样硬化发病中具有重要的作用。近年来研究认为其介导的慢性炎症反应可能参与高血压左室肥厚的发病过程,但也有报道持相反观点。丹参酮ⅡA是丹参的一种脂溶性提取性,动物实验证明其具有抑制高血压左室肥厚发生的作用。目的:探讨细胞间黏附分子1在高血压左室肥厚发生中的作用及丹参酮ⅡA对其表达的影响。设计:随机对照观察。单位:华中科技大学同济医学院附属同济医院。材料:实验于2002-10/2004-01在华中科技大学同济医学院附属同济医院急诊科实验室完成,选用12周龄雄性WKY大鼠10只、自发性高血压SHR大鼠20只,分为对照组(WKY大鼠10只)、高血压组(SHR大鼠10只)、丹参酮ⅡA组(SHR大鼠10只)。方法:丹参酮ⅡA组经尾静脉注射丹参酮ⅡA1.5mg/(kg·d)治疗,其他两组分别注射等量的蒸馏水。12周后断头处死所有大鼠留取心肌标本,应用苏木精-伊红染色、VG染色,免疫组化染色及心肌ED1标记检测心肌巨噬细胞浸润数,心肌细胞间黏附分子1mRNA及蛋白的表达应用反转录-聚合酶链反应及酶链免疫吸附实验等方法。主要观察指标:各组大鼠心肌巨噬细胞浸润数,心肌细胞间黏附分子1mRNA及蛋白表达。结果:20只SHR和10只WKY大鼠被纳入实验,并全部进入结果分析,无脱失值。①与对照组比较,高血压组大鼠肥厚心肌中细胞间黏附分子1的mRNA及蛋白表达显著增加(0.176±0.087,0.537±0.195;0.104±0.011,0.173±0.027,P<0.01或P<0.05),巨噬细胞浸润明显(0.62±0.07,1.85±0.23,P<0.01)。②与高血压组比较,丹参酮ⅡA组大鼠心肌细胞间黏附分子1的mRNA及蛋白表达水平显著下调(0.537±0.195,0.291±0.106;0.173±0.027,0.125±0.014,P<0.01或P<0.05),巨噬细胞浸润数减少(1.85±0.23,1.16±0.17,P<0.05),心肌细胞肥大和间质纤维化程度明显减轻。结论:心肌细胞间黏附分子1的过度表达及其介导的炎性细胞浸润在高血压左室肥厚的发病过程中具有重要作用。丹参酮ⅡA抑制左室肥厚的效应可能与其下调细胞间黏附分子1表达,减少炎性细胞的心肌浸润有关。
BACKGROUND: Intercellular adhesion molecule-1 plays an important role in the pathogenesis of atherosclerosis as a reliable marker of inflammation. In recent years, studies suggest that its mediated chronic inflammatory response may be involved in the pathogenesis of hypertensive left ventricular hypertrophy, but there are also reports of the opposite view. Tanshinone Ⅱ A is a fat-soluble extract of Salvia, animal experiments show that it has the role of inhibiting the occurrence of hypertension in patients with left ventricular hypertrophy. Objective: To investigate the role of intercellular adhesion molecule-1 in the development of left ventricular hypertrophy in hypertensive rats and the effect of tanshinone Ⅱ A on its expression. Design: Randomized controlled observation. Unit: Tongji Medical College Affiliated Tongji Hospital Huazhong University of Science and Technology. MATERIALS: The experiment was performed in the laboratory of emergency department of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from October 2002 to January 2004. Ten male WKY rats of 12 weeks old and 20 SHR rats of spontaneous hypertension were divided into The control group (10 WKY rats), the hypertension group (10 SHR rats) and the tanshinone Ⅱ A group (10 SHR rats). Methods: Tanshinone ⅡA group was treated with tanshinone ⅡA 1.5 mg / (kg · d) through caudal vein, and the other two groups were injected with the same amount of distilled water respectively. Twelve weeks later, all the rats were sacrificed and all the rats were sacrificed. Cardiomyocytes were harvested from the hearts of all rats. The numbers of myocardial macrophages, myocardial cells intercellular adhesion molecule-1 mRNA and protein were detected by hematoxylin-eosin staining, VG staining, immunohistochemistry and ED1 labeling. The application of reverse transcription - polymerase chain reaction and enzyme-linked immunosorbent assay methods. MAIN OUTCOME MEASURES: Myocardial macrophage infiltration number, ICAM-1 mRNA and protein expression in each group. Results: Twenty SHR and 10 WKY rats were included in the experiment and all of them were included in the result analysis without loss of value. ①Compared with the control group, the mRNA and protein expression of ICAM-1 in hypertensive myocardium were significantly increased in hypertension group (0.176 ± 0.087,0.537 ± 0.195; 0.104 ± 0.011,0.173 ± 0.027, P <0.01 or P <0.05 ), Macrophage infiltration (0.62 ± 0.07, 1.85 ± 0.23, P <0.01). ②Compared with the hypertensive group, the mRNA and protein expression of ICAM-1 in tanshinoneⅡA group were significantly decreased (0.537 ± 0.195,0.291 ± 0.106; 0.173 ± 0.027,0.125 ± 0.014, P <0.01 or P <0.05 ), The number of macrophages infiltration decreased (1.85 ± 0.23, 1.16 ± 0.17, P <0.05), and the degree of myocardial hypertrophy and interstitial fibrosis significantly reduced. Conclusion: The overexpression of ICAM-1 and its involvement in inflammatory cell infiltration play an important role in the pathogenesis of hypertension-induced left ventricular hypertrophy. The effect of tanshinone ⅡA on left ventricular hypertrophy may be related to down-regulation of intercellular adhesion molecule-1 expression and decrease of myocardial infiltration in inflammatory cells.