摘要
目的研究丹参酮ⅡA(TSN)对腹主动脉缩窄大鼠肥厚心肌血管紧张素1型受体(AT1R)、一氧化氮合酶(eNOS)及蛋白激酶C(PKC)基因表达的影响,探讨丹参酮ⅡA抑制高血压左心室肥厚的分子机制。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,ip)、缬沙坦组(10 mg·kg-1·d-1,ig),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)、病理切片HE染色测量心肌纤维直径(MFD);采用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)检测AT1R mRNA的表达水平、免疫印迹法(Western blotting)分别检测eNOS的蛋白水平和PKC的活性。结果①TSN低、高剂量均对血压没有影响,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)。④TSN低、高剂量都可使肥厚心肌的AT1R mRNA和PKC蛋白水平明显下调(P<0.01),对PKC的下调作用超过缬沙坦组(P<0.05)。结论丹参酮ⅡA对心肌肥厚的抑制作用是非血压依从性的,其对高血压心肌肥厚的抑制作用可能与抑制AT1R的mRNA和PKC蛋白的表达量、促进心肌局部NO的产生及eNOS蛋白的表达有关。
OBJECTIVE To explore the molecular mechanism for tanshinone ⅡA reversing left ventricular hypertrophy,which involved the effect of tashinone on the angiotensin Ⅱ type 1 receptor and endothelial nitric oxide synthase（eNOS） and protein kinase C（PKC） in the hypertrophic cadiocyte of rats suffered abdominal aorta constriction.METHODS SD rats were operated with abdominal aorta constriction and 8 rats were done with artificial surgery.After 4 weeks,all rats were divided into 4 groups： myocardial hypertrophy group,low dose tanshinone ⅡA group（10 mg·kg^-1·d^-1,ip）,high dose tanshinone ⅡA group（20 mg·kg^-1·d^-1,ip） and valsartan group（10 mg·kg^-1·d^-1,ig）.Eight weeks later,measuring 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 AT1 receptor by RT-PCR and to detect the activity of eNOS and PKC by Western blotting.RESULTS ①The tanshinone ⅡA at either low or high dosage has not effect on the blood pressure,which remains significantly hihgher than the artificial surgery and valsartan groups（P〈0.01）.②The LVMI and MFD in both tanshinone ⅡA at either dosage and valsartan groups are significantly lower than those of the surgery group（P〈0.01）,although higher than the artificial surgery group（P〈0.05）.③The amount of NO and eNOS expression in both tanshinone ⅡA at either dosage and valsartan groups are higher than the surgery group（P〈0.01）,and the up-regulation of eNOS in tanshinone ⅡA group at either dosage is more prominent than in valsartan group（P〈0.05）.④Tanshinone ⅡA at either dosage could significantly down-regulate the AT1R mRNA and PKC level in the hypertrophic cardiomyocyte（P〈0.01）,with more prominent effect on down-regulating PKC expression than valsartan group（P〈0.05）.CONCLUSION NO/NOS system in local myocardium had close relationship
出处
《中国药学杂志》
CAS
CSCD
北大核心
2008年第17期1313-1317,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30500657)
