摘要
目的本文利用离体结合在体实验探讨心肌营养素-1(CT-1)在高血压心室重塑中的作用。方法离体实验用160 mm Hg的高静水压刺激原代培养的心肌成纤维细胞,同时用心肌营养素-1的反义寡核苷酸进行干预。分别用MTT法检测心肌成纤维细胞的增殖,放免法检测血管紧张素Ⅱ的浓度,Western blotting检测CT-1蛋白的表达。以L-NAME诱导的一氧化氮缺乏性高血压大鼠作为在体实验模型。用卡托普利进行干预。12周后处死动物,取材观察心肌组织病理变化,检测心肌中血管紧张素Ⅱ及羟脯氨酸的浓度,同时检测心肌中CT-1的表达。结果高静水压能明显促使心肌成纤维细胞增殖,血管紧张素Ⅱ分泌增加,CT-1合成上调(光密度值1.56±0.24 vs 0.95±0.19,P<0.01),而CT-1的反义寡核苷酸能抑制高静水压诱导的细胞增殖和血管紧张素Ⅱ分泌。而进行在体实验的大鼠给予L-NAME后血压明显升高,心肌组织中血管紧张素Ⅱ和羟脯氨酸分泌增加,CT-1表达上调(光密度值1.79±0.21vs 1.02±0.12,P<0.01),经卡托普利干预后,与L-NAME组相比,血压明显下降,心肌组织中羟脯氨酸浓度降低,血管紧张素Ⅱ分泌减少,CT-1表达下调(1.12±0.15 vs 1.79±0.21,P<0.05)。结论从在体和离体实验证明CT-1在高血压心室重塑中发挥着重要的调节作用,且这一作用与肾素血管紧张素系统有关。
Objective To investigate the effect of cardiotrophin-1 （CT-1） on the hypertensive ventricular remodeling. Methods Cardiac fibroblasts were cultured in the presence of high hydrostatic pressure （ 160 mm Hg）, or treated with antisense oligodeoxynucleotide of CT-1. The proliferation of cardiac fibroblasts, concentration of Ang Ⅱ and expression of CT-1 were determined by MTT, radioimmunoassay or Western blotting, respectively. In vivo, chronic L-NAME induced hypertensive rats Were treated with captopril（ 50 mg/kg.d） for 8 weeks. Rats were sacrified after 12 weeks. Ventricular morphometry was analyzed, and Ang Ⅱ and hydroxyproline level in myocardiac tissue were measured. LV expression of CT-1 was examined by Western blotting. Results The cardiac fibroblasts proliferation, CT-1 expression optical density（OD） （ 1.56±0.24 vs control： 0. 95±0. 19, P〈0. 01 ） and secretion of Ang ± were enhanced by high hydrostatic pressure, and inhibited by the ASODN of CT-1. After L-NAME administration, BP of rat increased raised significantly which was associated with the increases in Ang Ⅱ and hydroxyproline and the expression of CT-1 in myocardium（ 1.79±0. 21 vs 1. 02±0.12, P〈0. 01 ）. Compared with the L-NAME group, the BP of Captopril group was lower, the contents of Ang Ⅱ and hydroxyproline were less, and the CT-1 expression was downregulated（ 1.12±0. 15 vs 1.79±0. 21, P〈 0. 05）. Conclusion CT-1 is likely to play a role in the hypertensive ventricular remodeling which may be relevant to the renin angiotensin system （RAS） .
出处
《高血压杂志》
CSCD
北大核心
2006年第4期294-298,共5页
Chinese Journal of Hypertension
