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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 observe the effect of atorvastatin on myocardial reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate oxidase (NAD (P) H oxidase) and activator protein 1 (AP-1 ), And to explore the mechanism of atorvastatin inhibiting cardiac hypertrophy. Methods The model of hypertension was established by two kidneys and two clamps. A total of 50 rats were divided into 5 groups with 10 rats in each group: sham operation control group (group A), model group (two rats and two rats, group B) + High-dose atorvastatin group (group C); low-dose two-kidney plus atorvastatin group (group D); two renal two-can + candesartan group (group E). Four weeks after the operation, the aortic pressure and left ventricular pressure were measured after carotid artery cannulation to the left ventricle 4 weeks after the administration. The left ventricular mass index (LVMI), morphological changes and the superoxide anion ( The expression of N47 (P) H oxidase subunits p47phox, NOX4 and AP-1 in the left ventricle were detected by Western blot. Results Compared with group A, left ventricular end-systolic pressure in group B was significantly higher than that in group A ([(171.0 ± 11.9) vs (104.0 ± 4.5) mmHg], LVMI [(2.1 ± 0.2) vs (1.1 ± 0.1) mg / (P <0.01). Compared with group B, LVMI in group C and D [(1.3 ± 0.1), (1.6 (P <0.05)]. The generation of O2- · in the ventricular muscle was significantly higher than that in the control group (P <0.01) (P <0.01). LVMI [(1.4 ± 0.1) vs (2.1 ± 0.2) mg / g, P <0.05 ], The generation of O2- · in the ventricular muscle [(415.0 ± 42.0) vs (805.0 ± 62.0), P <0.01] was significantly decreased. Compared with group A, the protein expression of p47phox, NOX4 and AP-1 in group B was significantly increased (P <0.01). Compared with group B, the expressions of p47phox, NOX4 and AP-1 in group C, D and E Significantly lower (P <0.01). Conclusions Atorvastatin can significantly inhibit left ventricular p47phox and NOX4 expression, decrease O2- · production and down-regulate the expression of transcription factor AP-1 in two-kidney and two-renal hypertensive rats, which may be related to the inhibition of myocardium The role of hypertrophy.