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背景:醛固酮是左心室肥厚重要的致病因子,有证据提示中药丹参提取物能够干预醛固酮的生物合成。目的:探讨丹参酮ⅡA对心肌醛固酮合成相关基因表达的作用。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2002-11/2004-03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周龄雄性自发性高血压SHR大鼠20只,随机分为高血压组、丹参酮ⅡA组,每组10只。方法:丹参酮ⅡA组经尾静脉注射丹参酮ⅡA溶液1.5mg/(kg·d),高血压组给予相当容积的蒸馏水。给药12周后断头处死大鼠,留取心肌标本,通过反转录-聚合酶链反应,以GAPDH基因扩增引物表为内参照,分别测定心肌醛固酮合成相关基因CYP11B1及CYP11B2mRNA表达。主要观察指标:心肌醛固酮合成相关基因CYP11B1及CYP11B2mRNA表达水平。结果:20只大鼠被纳入实验,并全部进入结果分析,无脱失值。①两组大鼠心肌CYP11B1及CYP11B2基因表达的定性分析:以100bpPlusLad-der为Marker,分别在440bp,461bp及336bp处可见清晰的扩增条带,DNA测序证实为CYP11B1,YP11B2及GAPDH的编码基因片段。②两组大鼠心肌CYP11B1及CYP11B2基因表达的定量分析:丹参酮ⅡA组CYP11B1及CYP11B2的mRNA表达水平明显低于高血压组(0.924±0.121,1.343±0.132,P<0.05;1.017±0.119,1.675±0.126,P<0.01)。结论:丹参酮ⅡA可能通过直接下调心脏局部醛固酮合成相关基因CYP11B1及CYP11B2mRNA表达,抑制心脏局部醛固酮的生物合成,从而发挥抗高血压左室肥厚的效应。
Background: Aldosterone is an important virulence factor of left ventricular hypertrophy, and there is evidence that Salvia miltiorrhiza extract can interfere with aldosterone biosynthesis. Objective: To investigate the effect of tanshinone II A on the expression of cardiac aldosterone synthesis related genes. Design: Randomized controlled observations. Unit: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: The experiment was performed at the Emergency Department Laboratory of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from November 2002 to March 2004. Twenty male 12-week-old male spontaneously hypertensive SHR rats were randomly divided into hypertension group and tanshinone group. Group IIA, 10 in each group. METHODS: The tanshinone IIA solution was injected into the tanshinone IIA group at a dose of 1.5 mg/(kg·d) via the tail vein. The hypertensive group received an equivalent volume of distilled water. Twelve weeks after administration, the rats were killed by decapitation. Myocardial specimens were collected and the expression of CYP11B1 and CYP11B2 mRNAs related to aldosterone synthesis was determined by reverse transcription-polymerase chain reaction (PCR) using GAPDH gene amplification primers as internal references. MAIN OUTCOME MEASURES: CYP11B1 and CYP11B2 mRNA expression levels of cardiac aldosterone synthesis genes. RESULTS: Twenty rats were included in the experiment and all entered the results analysis without loss of value. 1 Qualitative analysis of CYP11B1 and CYP11B2 gene expression in rat myocardium: 100bpPlusLad-der was used as marker, and clear bands were seen at 440bp, 461bp and 336bp, respectively. DNA sequencing confirmed the genes encoding CYP11B1, YP11B2 and GAPDH. Fragment. 2 Quantitative analysis of myocardial CYP11B1 and CYP11B2 gene expression in two groups: The mRNA expression of CYP11B1 and CYP11B2 in tanshinone IIA group was significantly lower than that in hypertension group (0.924±0.121, 1.343±0.132, P<0.05; 1.017±0.119, 1.675± 0.126, P < 0.01). CONCLUSION: Tanshinone IIA may exert anti-hypertensive effects on left ventricular hypertrophy by directly down-regulating the expression of CYP11B1 and CYP11B2 mRNAs involved in cardiac local aldosterone synthesis and inhibiting aldosterone biosynthesis in the heart.