中国中药杂志

2008, (12) 1446-1450

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丹参酮Ⅱ_A对大鼠肥厚心肌NO产生及eNOS基因表达的影响
Effect of tashinone on nitric oxide synthase in hypertrophic cadiocyte of rats suffered abdominal aorta constriction

李永胜;王照华;严丽;雍永权;王进;梁黔生;郑智;杨光田;
LI Yong-sheng WANG Zhao-hua YAN Li YONG Yong-quan WANG Jin LIANG Qian-sheng ZHENG Zhi YANG Guang-tian (Department of Emergency Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

摘要(Abstract):

目的:研究丹参酮Ⅱ_A(TSN)对腹主动脉缩窄大鼠肥厚心肌一氧化氮合酶及蛋白激酶C的影响,探讨丹参酮Ⅱ_A逆转高血压左心室肥厚的分子生物学机制。方法:SD大鼠行腹主动脉缩窄术建立高血压左室心肌肥厚模型。术后4周将手术大鼠随机分为手术组、TSN低、高剂量组(10,20 mg·kg~(-1)·d~(-1),腹腔注射)、缬沙坦组(10 mg·kg~(-1)·d~(-1),灌胃),每组8只;另有8只作为假手术组。用药8周后检测各组尾动脉压,取左心室组织检测左心室质量指数(LVMI)、心肌纤维直径(MFD);硝酸还原法测定心肌组织NO的含量,逆转录-聚合酶链式反应(RT- PCR)、免疫印迹法(Western blotting)分别检测eNOS的基因表达水平和蛋白激酶C(PKC)的活性。结果:①TSN低、高剂量组的血压仍显著高于假手术组和缬沙坦组(P<0.01)。②TSN低、高剂量组和缬沙坦组的LVMI,MFD虽然高于假手术组(P<0.05),却显著低于手术组(P<0.01)。③TSN低、高剂量组和缬沙坦组的NO含量以及eNOS蛋白、mRNA表达水平明显高于手术组(P<0.01),TSN两组的eNOS上调超过缬沙坦组(P<0.05)。④手术组的PKC蛋白水平显著升高(P<0.01),TSN低、高剂量组PKC水平明显低于缬沙坦组(P<0.05)。结论:丹参酮Ⅱ_A对心肌肥厚的逆转作用是非血压依从性的,丹参酮Ⅱ_A通过抑制PKC蛋白的表达、促进心肌局部NO的产生及eNOS基因表达,起到阻止、逆转高血压心肌肥厚的发展。
Objective:To explore the molecular biological mechanism for tanshinoneⅡ_A reversing left ventricular hypertrophy, it would be studying the effect of tashinone on the endothelial nitric oxide synthase(eNOS)and protein kinase C(PKC)in the hyper- trophic cadiocyte of rats suffered abdominal aorta constriction.Method:SD rats were operated with abdominal aorta constriction and 8 rats were done with sham surgery.After 4 weeks,all rats were divided into 4 groups:myocardial hypertrophy group,low dose tanshi- noneⅡ_A group(10 mg·kg~(-1)·d~(-1)),high dose tanshinoneⅡ_A group(20 mg·kg~(-1)·d~(-1))and valsartan group(10 mg·kg~(-1)·d~(-1) intragastric administration).8 weeks later,the rats were used to measure the left ventricular mass index(LVMI)with the tissue of left ventricle and myocardial fiber dimension(MFD)by pathological section and HE stain,to detect the nitric oxide content by nitrate reductase,to detect the genic expression of eNOS by RT-PCR and to detect the activity of protein kinase C(PKC)by Western blot- ting.Result:①The blood pressure in group myocardial hypertrophy[(186±13)mmHg]and tansginoneⅡ_A[low and high dose (188±11,187±14)mmHg]was obviously higher than that in group sham surgery and valsartan group[vs(117±8,136±15)mm- Hg,P<0.01].But there was no difference between group myocardial hypertrophy and group tanshinoneⅡ_A(low and high dose).②The LVMI and MFD were obviously higher in group tanshinoneⅡ_A(low and high dose)and group valsartan than those in group sham surgery(P<0.05),and lower than those in group myocardial hypertrophy(P<0.01).③The NO level was obviously higher in group tanshinoneⅡ_A(low and high dose)and group valsartan than that in group myocardial hypertrophy(12.78±1.66,11.95±1.39, 12.26±2.08 vs 5.83±1.06)μmol·L~(-1)(p<0.01),and lower than that in group sham surgery(vs 19.35±1.47)μmol·L~(-1), (P<0.05).④The expressive level of eNOS mRNA and protein in myocardial hypertrophy group was less than that in other groups (P<0,01).And valsartan group was less than tanshinoneⅡ_A groups and sham surgery group(P<0.05),but there were no differ- ence among the two tanshinoneⅡ_A groups and sham surgery group.⑤The level of PKC protein in group myocardial hypertrophy was obviously higher than that in all the other groups(1.291±0.117 vs 0.563±0.094,0.605±0.051,0.519±0.062,0.827±0.086, P<0.01),and the level in group valsartan was higher than that in group sham operation and group tanshinoneⅡ_A(low and high dose).Conclusion:NO/NOS system in local myocardinm has close relationship with the pathological process for myocardial hypertro- phy.TanshinoneⅡ_A can produce the pharmacological action to reverse myocardial hypertrophy by inhibiting the activity of PKC and promoting the genic expression of eNOS in local myocardium and the production of endogenous NO.

关键词(KeyWords): 丹参酮Ⅱ_A;压力超负荷;心肌肥厚;内皮型一氧化氮合酶;蛋白激酶C;基因表达
tanshinoneⅡ_A;pressure ovedoad;hypertrophic myocardium;nitric oxide synthase;protein kinase C;genie expression

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(30500657)

作者(Author): 李永胜;王照华;严丽;雍永权;王进;梁黔生;郑智;杨光田;
LI Yong-sheng WANG Zhao-hua YAN Li YONG Yong-quan WANG Jin LIANG Qian-sheng ZHENG Zhi YANG Guang-tian (Department of Emergency Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

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