替米沙坦对高盐饮食诱导大鼠心肌重构的影响  

Effects of telmisartan on myocardial remodeling in Wistar rats induced by high-salt diet

作　　者：石耿辉[1,2] 商黔惠[1,2] 吴芹[1,3] 王晓春[1,2] 

机构地区：[1]遵义医学院临床医学研究所 [2]遵义医学院附属医院心内科,贵州遵义563003 [3]遵义医学院附属医院药理学教研室,贵州遵义563003

出　　处：《中华高血压杂志》2013年第8期746-752,共7页Chinese Journal of Hypertension

基　　金：贵州省社会发展攻关计划项目和省高层次人才科研条件特助项目[黔科合SY字(2011)3047号,TZJF-2009年-42];国家自然科学基金资助项目(81160041)

摘　　要：目的观察高盐饮食对Wistar大鼠心肌重构的影响,探讨替米沙坦逆转左心室重构的可能机制。方法49只Wistar大鼠经高盐饲养后随机分为高盐高血压组[n=12,NaCl约2.015g/(只·d)]和高盐正常血压组[n=12,NaCl约2.015g/(只·d)],同时设立对照组[n=13,NaCl约0.094g/(只·d)]和替米沙坦组[n=12,NaCl约1.966g/(只·d)]。采用HE和Masson染色观察心肌组织形态和结构变化。生化酶学法测定血液及左心室中超氧化物歧化酶(SOD)活性和丙二醛浓度,酶联免疫吸附试验(ELISA)测定血清高敏C反应蛋白(hsCRP)浓度,放射免疫法测定心肌肿瘤坏死因子α(TNF-α)浓度,Western blot法检测心肌核转录因子κB(NF-κB)p65蛋白表达水平。结果与对照组比较,高盐两组左心室质量指数(LVMI)、心肌细胞直径(CMD)、心肌间纤维化面积(MIFI)、hsCRP、左心室TNF-α浓度、NF-κB p65蛋白表达水平及血清SOD活性明显升高(均P<0.05),但左心室SOD活性降低;心肌重构(LVMI、CMD、MIFI)与左心室SOD活性呈负相关[分别r=-0.448、-0.625、-0.492,均P<0.05],与NF-κB蛋白表达水平呈正相关[r=0.556、0.693、0.803,均P<0.05];替米沙坦能改善高盐诱导的左心室重构,并增强左心室SOD活性[替米沙坦组(72.20±12.17)比高盐高血压组(58.34±5.78)、高盐正常血压组(54.59±6.65)U/mg pro,P<0.05]、降低高盐正常血压组左心室TNF-α[替米沙坦组(45.56±6.97)比高盐正常血压组(56.67±9.67)ng/g,均P<0.05]和高盐高血压组NF-κB[替米沙坦组(62.79±9.00)比高盐高血压组(87.77±10.30),P<0.05]表达水平。结论长期高盐饮食可导致Wistar大鼠心肌重构;氧化应激和炎症反应可能参与高盐诱导心肌重构的机制;替米沙坦可能部分通过抑制氧化应激、炎症反应,从而减轻高盐诱导的心肌重构。Objective To study the effects of telmisartan on myocardial remodeling in Wistar rats induced by high salt diet and its mechanism. Methods Twenty-four Wistar rats fed by high salt diet for twenty-four weeks which were divided into two groups： high salt hypertension group[ HSH,n= 12, NaC1 2. 015 g/（only · d）]and high salt normal blood pressure group[HSN, n= 12, NaC1 2. 015 g/（only · d）] according to the level of systolic blood pressure （SBP）. The rats fed only with normal-salt were used as controls[n= 13, NaC1 0. 094 g/（only· d）]and fed with telmisartan use as telmisartan group[n= 12, NaC1 1. 966 g/（only · d）]. Myocardial morphological and structural changes were observed by Hematoxylin-eosin staining （HE） and Masson staining. The level of superoxide dismutase （SOD） and malondialdehyde in blood, as well as left ventricle （LV） were measured by biochemistry and enzymolo- gy. The level of tumor necrosis factor a （TNF-a） and high-sensitivity C-reactive protein （hsCRP） were determined by radioimmunoassay and enzyme linked immunosorbent assay （ELISA）. The expression of nuclear factor-κB p65 （NF-κB p65） was evaluated by Western blot. Results Compared with NS group, the level of LVMI, cardiomyocyte diameter （CMD）, area of myocardial fibrosis （MIFI）, hsCRP, TNF-α, NF-κb p65 and serum SOD were significantly increased （all P〈0.05） in HSN and HSH group, while the activity of SOD in LV was decreased. The LVMI,CMD and MIFI were negatively correlated with SOD activity in LV {r=- 0. 448, --0. 625, -0. 492, respectively; all P〈0.05） and positively correlated with the expression of NF-~cB p65 {r=0. 556, 0. 693, 0. 803, respectively; all P〈0.05）. Telmisartan partly reversed myocardial remodeling, increased the SOD activity in LV[{72. 204.12.17） vs {54. 59±6.65） U/rag pro, P〈0.05] and [（72.20~12.17} vs （58. 344.5.78）, P〈0.05] as compared to HSN and HSH group. Compared with telmisartan group, the expression of NF-KB p65 in HSH[（87.77 ± 10

关 键 词：盐 心肌重构 超氧化物歧化酶 核转录因子ΚB 肿瘤坏死因子α 高敏C反应蛋白 替米沙坦 

分 类 号：R965[医药卫生—药理学]