摘要
目的观察阿托伐他汀对肾性高血压大鼠心肌活性氧生成、还原型烟酰胺腺嘌呤二核苷酸(磷酸)氧化酶[NAD(P)H氧化酶]及活化蛋白1(AP-1)表达的影响,探讨阿托伐他汀抑制心肌肥厚的作用机制。方法用两肾两夹法建立高血压模型,共50只分5组,每组10只:假手术对照组(A组);模型组(两肾两夹组,B组);两肾两夹+阿托伐他汀高剂量组(C组);两肾两夹+阿托伐他汀低剂量组(D组);两肾两夹+坎地沙坦组(E组)。术后4周进行药物处理,给药4周后颈动脉插管至左心室测定主动脉压及左心室内压,并观察左心室质量指数(LVMI)、形态学变化、心室肌超氧阴离子(O2-·)的生成,Westernblot检测左心室NAD(P)H氧化酶亚基p47phox、NOX4及AP-1的表达情况。结果与A组比较,B组大鼠左心室收缩末压[(171.0±11.9)比(104.0±4.5)mmHg]、LVMI[(2.1±0.2)比(1.1±0.1)mg/g]、心室肌中O2-·的生成[(805.0±62.0)比(233.0±29.0)]明显升高(均P<0.01);与B组比较,C、D组大鼠LVMI[(1.3±0.1)、(1.6±0.4)比(2.1±0.2)mg/g,P<0.05]、心室肌中O2-·的生成[(385.0±37.0)、(495.0±44.0)比(805.0±62.0),P<0.01]明显减弱,E组大鼠左心室收缩末压[(107.0±4.8)比(171.0±11.9)mmHg,P<0.01]、LVMI[(1.4±0.1)比(2.1±0.2)mg/g,P<0.05]、心室肌中O2-·的生成[(415.0±42.0)比(805.0±62.0),P<0.01]明显降低。与A组比较,B组大鼠p47phox、NOX4及AP-1的蛋白表达明显增加(P<0.01);与B组比较,C、D、E组左心室p47phox、NOX4及AP-1蛋白表达均明显降低(P<0.01)。结论阿托伐他汀能明显抑制两肾两夹肾性高血压大鼠左心室p47phox和NOX4的表达,减少O2-·的生成,同时可下调转录因子AP-1的表达,该作用可能与其抑制心肌肥厚的作用有关。
Objective To investigate the effects of atorvastatin on the production of reactive oxygen species, the ex- pressions of reduced form of nicotinamide-adenine dinucleotide（phosphate） oxidases, active protein-1 （ AP- 1 ） ; and its mechanism in cardiac hypertrophy inhibition in renal hypertensive rats. Methods Two kidney two clip tech- nique （2K2C） was used to establish rat hypertension models. A total of 50 rats were divided into five groups： sham-operated rats （group A） ; 2K2C rats （group B） ; group B plus atorvastatin [5 or 10 mg/（kg · d）, group C and D]; group B plus candesartan [10 mg/（kg · d）, group E] （all n= 10 ）. Four weeks after surgery, rats received treat- ment for 4 weeks. After treatment, left ventricular（LV） hemodynamic studies were performed by cannulation of the right carotid artery, then the rats were euthanized and left ventricular mass index （LVMI）, morphological changes, the generation of O2-＇ in ventricular muscle were measured. The expressions of left ventricular NAD（P} H oxi- dase subunit[-p47phax], NOX4 and AP-1 were detected by Western blot. Results Compared to group A, the end systolic blood pressure [-（rate of 02 - in ventricular muscle [（ 805.0 ± 62.0 ） vs （ 233.0 ± 29.0 }] were markedly elevated in group B （all P〈0.01）. Compared to group B, the LVMI[（1.3±0.1）, （1.6±0.4} vs （2. l±0.2}mg/g, P〈 0.05], the generation rates of O2-＇ in ventricular muscle [（385. 0±37. 0） , （495.0±44.0） vs （805.0±62.0）, P〈0.01] in C and D groups were significantly decreased; and the end systolic blood pressure [（107.0±4.8） vs （171.0±11.9）ram Hg, P%0.01], the LVMI[（1.4±0.1） vs （2.1±0.2）mg/g, P〈0.05] and the generation rate of 02 - in ventricular muscle [（415.0±42.0} vs （805.0±62.0}, P%O. 01] in group E were significantly reduced. Compared to group A, the protein expressions of p47phax , NOX4 and AP-1 in group B were significantly increased （P〈0.01）, while the protein expressions of the
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2012年第11期1071-1075,共5页
Chinese Journal of Hypertension
基金
河南科技大学创新能力培育基金项目(2009CZ0008)
