Objective To observe the effect of telmisartan on the level of serum adiponectin and the expression of cardiac adiponectin (APN) receptor 1 in spontaneously hypertensive rats (SHR) in order to explore the role of APN in ventricular remodeling caused by hypertension and the new possible mechanism that telmisartan protects the heart against ventricular remodeling.Methods The sixteen 12-week-old SHR were randomly divided into SHR control group (SHR group, n=8) and SHR+telmisartan group (TEL group, n=8), and eight age-matched male Wistar Kyoto rats were regarded as control group (WKY group). The TEL group was treated with telmisartan 5 mg-1 · kg-1 ·d-1 in a small amount of distilled water and the other two groups were given equal amount of distilled water by gavage. After 8 weeks, the left ventricular end diastolic diameters (LVEDD),thickness of interventricular septal thickness (IVST), left ventricular post wall thickness (LVPWT) and mitral valve blood flow spectrums were recorded by echoeardiograph. The E/A ratio was calculated by velocity of E peak divided by A peak. The left ventricular weight index (LVWI) was calculated. HE staining and Masson staining were used to detect the pathology changes of cardiac tissue and collagen volume fraction (CVF). Serum APN concentration of SHR was detected by enzyme-linked immunosorbent assay (ELISA). The myocardial protein expression of AdipoR1 was detected by in munohistochemical staining. Reverse transcription polymerase chain reactions (RTPCR) method was used to detect the mRNA expression of AdipoRl in myocardium.Results The values of IVST, LVPWT and LVWI were higher, LVEDD and E/A ratio were lower in SHR group than in WKY group. The disordered arrangement of myocardial cells, interstitial fibroblast hypertrophy and hyperplasia were observed in SHR group. The CVF increased in SHR group than in WKY group [(6.22±0.16)％ vs. (3. 18±0. 17)％, P＜0.05]. The concentration of serum APN was significantly lower in SHR group [( 10.96±2. 15)μg/ml vs. (24.32±2. 20)μg/ml, P＜0. 01].The expressions of myocardial AdipoR1 mRNA and protein were significantly lower in SHR group.The values of IVST, LVPWT and LVWI were lower, LVEDD and E/A ratio were higher in TEL group than in SHR group. The arrangement of myocardial cells were relatively ordered and interstitial fibroblasts hypertrophy and hyperplasia were not significant, CVF was decreased in TEL group versus SHR group. The concentration of serum APN was significantly higher in TEL group [(17.71 ± 5.82)μg/ml, P＜0. 01]. The expressions of myocardial AdipoR1 mRNA and protein were significantly higher in TEL group than in SHR group. Conclusions When SHR undergoes ventricular remodeling, the level of serum APN is lower, the mRNA and protein expressions of myocardial AdipoRl are significantly reduced. Telmisartan can reverse the ventricular remodeling and play the role in protecting heart in SHR, which may be due to the serum APN levels increasing, cardiac APN receptor 1 and its mRNA up-regulation.%目的 研究替米沙坦对自发性高血压大鼠(SHR)血清脂联素水平及心肌脂联素受体1(AdipoR1)表达的影响,探讨脂联素在高血压心室重构中的作用及替米沙坦抑制逆转心室重构的机制. 方法 16只12周龄SHR随机分为SHR对照组8只,SHR+替米沙坦(干预组)8只,同周龄的雄性京都Wistar大鼠(WKY)8只为正常血压对照组(WKY组).干预组给予替米沙坦5 mg-1·kg-1·d-1混悬于少量蒸馏水灌胃治疗,其余两组给予等量蒸馏水灌胃.喂养8周后,各组大鼠分别用超声心动图测定左心室舒张末期内径(LVEDD)、室间隔厚度(IVST)、左心室后壁厚度(LVPWT)、二尖瓣口舒张早期峰值流速(E峰)、舒张晚期血流峰值流速(A峰),并计算E/A比值;计算左心室质量指数(LVWI);HE染色和Masson染色观察心肌组织形态学改变,并测定心肌胶原容积分数(CVF);酶联免疫吸附法(ELISA)检测SHR大鼠血清脂联素浓度;免疫组织化学方法检测心肌组织AdipoR1蛋白表达水平;反转录聚合酶链反应(RT-PCR)检测心肌组织AdipoR1mRNA表达水平. 结果与WKY组比较,SHR组1VST、LVPWT、LVWI均增加(均P＜0.05);LVEDD和E/A均减小;心肌细胞排列紊乱,间质成纤维细胞肥大增生,CVF增大;血清脂联素水平降低(10.96±2.15)mg/L与(24.32±2.20)mg/L,差异有统计学意义(P＜0.01);AdipoR1mRNA及AdipoR1蛋白表达均降低.与SHR组比较,干预组IVST、LVPWT、LVWI均减小(P＜0.05);LVEDD和E/A增大(P＜0.05);心肌细胞排列较整齐,间质成纤维细胞肥大增生不明显,CVF减小;血清脂联素水平增高,为(17.71±5.82)mg/L,P＜0.01;AdipoR1mRNA及AdipoR1蛋白表达均增高. 结论SHR大鼠发生心室重构,血清脂联素水平显著降低,心肌AdipoR1 mRNA和AdipoR1蛋白表达水平下调,替米沙坦可能通过使血清脂联素水平升高,心肌脂联素受体1及其mRNA表达上调,从而抑制逆转SHR大鼠高血压心室重构,起到保护心脏作用.
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