多肽化合物urantide抑制动脉粥样硬化大鼠心脏Ⅰ型胶原的表达

doi:10.16098/j.issn.0529-1356.2020.01.018

摘要/Abstract

摘要：

目的观察多肽类化合物urantide对动脉粥样硬化（As）大鼠心脏组织中Ⅰ型胶原（ColⅠ）表达的影响，探讨其防治损伤的作用机制。方法选取健康雄性3周龄SPF级Wistar大鼠60只，采用腹腔注射维生素D3（VD3）损伤动脉内膜及高脂饲料饲养的方法建立大鼠As模型，随机分为：正常组、As模型组、辛伐他汀组和urantide（3 d、7 d、14 d）组。采用HE染色和Masson三色染色方法，观察大鼠心脏组织形态和胶原纤维表达，免疫组织化学、Western blotting和Real-time PCR方法检测大鼠心脏Col Ⅰ蛋白和基因的表达。结果与正常组相比，As模型组大鼠心脏组织中出现心肌细胞变性，细胞间浸润大量的中性粒细胞，且有散布的泡沫细胞及充血出血等病理现象，同时胶原纤维增加，ColⅠ的基因和蛋白表达水平升高。与As模型组相比，经urantide治疗后心脏病理现象有缓解。随着给药时间的延长，胶原纤维减少，ColⅠ的基因和蛋白表达水平逐渐下调，尤以给药14 d时效果最佳。

结论 Urantide可抑制As大鼠心脏组织ColⅠ表达以缓解心肌间质损伤，对As大鼠的心脏具有保护作用。

关键词: Urantide；动脉粥样硬化, Ⅰ型胶原, 心肌纤维化, 免疫印迹法, 实时定量聚合酶链反应, 大鼠

Abstract:

Objective To observe the effect of the peptide compound urantide on the expression of type Ⅰ collagen (Col Ⅰ) in the heart tissue of rats with atherosclerosis (As), and to explore its mechanism of prevention and treatment of heart damage in As rats. Methods Sixty healthy male 3-week-old SPF Wistar rats were selected. The As model was established by intraperitoneal injection of vitamin D3 (VD3) to damage the arterial intima and high-fat diet. They were randomly divided into normal group, As model group, simvastatin group and urantide (3 days, 7 days, 14 days) groups. HE staining and Masson trichrome staining were used to observe the morphology and collagen fiber expression of rat hearts. Immunohistochemistry, Western blotting and Real-time PCR were used to detect the expression of Col Ⅰ protein and gene in rat heart. Results Compared with the normal group, pathological phenomena such As myocardial cell degeneration, intercellular infiltration of a large number of neutrophils, scattered foam cells and hyperemia and hemorrhage were observed in the heart tissues of the As model group. Meanwhile, collagen fibers increased, and the gene and protein expression levels of Col Ⅰ increased. Compared with the As model group, the cardiac pathological phenomena were effectively alleviated after the treatment with urantide. With the extension of the administration time, the collagen fibers decreased, and the gene and protein expression levels of Col Ⅰ were gradually dow-regulated, especially the effect was the best when the drug was given for 14 days. Conclusion Urantide can inhibit the expression of Col Ⅰ in As heart to reduce myocardial interstitial damage, and has a protective effect on the heart of As rats.

Key words: Urantide, Atherosclerosis, Type Ⅰ collagen, Myocardial fibrosis, Western blotting, Real-time PCR, Rat

中图分类号:

R363

杨舒涵王博孙美莎曹宇光王怡宁崔海鹏赵娟. 多肽化合物urantide抑制动脉粥样硬化大鼠心脏Ⅰ型胶原的表达[J]. 解剖学报, 2020, 51(1): 103-108.

YANG Shu-han WANG Bo SUN Mei-sha CAO Yu-guang WANG Yi-ning CUI Hai-peng ZHAO Juan. Polypeptide compound urantide inhibiting expression of typeⅠcollagen in rat heart of atherosclerosis[J]. Acta Anatomica Sinica, 2020, 51(1): 103-108.

参考文献

［1］ Xin C, Tang YJ, Gao M, et al. Prenatal exposure to lipopolysaccharide results in myocardial fibrosis in rat offsping［J］. Int J Mol Sci, 2016, 16(5): 10986-10996.

［2］ Octavian I, Anca MO, Gabriela CN, et al. Myocardial interstitial fibrosis-histological and immunohistochemical aspects［J］. Rom J Morphol Embryol, 2015, 56(4): 1473-1480.

［3］ Tian XQ, Wan XS,Yang JC, et al. The relationship between serum type Ⅰ collagen carboxy terminal peptide and matrix metalloprotein-2 level and coronary artery disease［J］. Chinese Journal of Evidence-Based Cardiovascular Medicine, 2016, 8(5):553-555. (in Chinese)

田祥全，万小松，杨纪才，等.血清Ⅰ型胶原羧基末端肽、基质金属蛋白-2水平与冠状动脉病变的关系［J］. 中国循证心血管医学杂志，2016，8(5)：553-555.

［4］ Zhao J, Xie LD, Song CJ, et al. Urantide improves atherosclerosis by controlling C-reactive protein, monocyte chemotactic protein-1 and transforming growth factor-β expression in rats［J］. Exp Ther Med, 2014, 7(6): 1647-1652.

［5］ Zhao J, Zhang SF, Shi Y, et al. Effects of urotensin Ⅱ and its specific receptor antagonist urantide on rat vascular smooth muscle cells［J］. Bosn J Basic Med Sci, 2013, 13(2): 78-83.

［6］ Huang ZY, Yang PY, Almoofti MR, et al. Comparative analysis of the proteome of left ventricular of heart atherosclerosis in rat［J］. Life Sci, 2004, 75(26): 3103-3115.

［7］ Jiao YB, Rui YC, Li TJ, et al. Expression of pro-inflammatory and anti-inflammatory cytokines in brain of atherosclerotic rats of effects Ginkgo biloba extract［J］. Acta Pharmacol Sin, 2005, 26(7): 835-839.

［8］ Li YL, Wen JF, Tang JW, et al. Pathology［M］. Beijing:People’s Medical Publishing House, 2013: 134-136. (in Chinese)

李玉林, 文继舫, 唐建武, 等. 病理学［M］. 北京:人民卫生出版社, 2013: 134-136.

［9］ Manduteanu I, Simionescu M. Inflammation in atherosclerosis: a cause or a result of vascular disorders ［J］? J Cell Mol Med, 2012, 20(10): 1582-1614.

［10］ Rathod RH, Powell AJ, Geva T.Myocardial fibrosis in congenital heart disease［J］. Circ J, 2016, 80(6): 1300-1307.

［11］ Cao H, Pang X, Wang Sh. Effect of Phenylephrine on myocardial fibrosis induced abdominal aorta construction in mice［J］. Chinese Journal of Arteriosclerosis, 2016, 24(11): 1097-1103. (in Chinese)

曹慧, 庞晓, 王硕. 苯肾上腺素对腹主动脉缩窄诱导心肌间质纤维化的影响［J］. 中国动脉硬化杂志, 2016, 24(11): 1097-1103.

［12］ Liang DY, Liu LM, Ye CG, et al. Inhibition of UⅡ/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice［J］. PLoS One, 2014, 8(6): e64895.

［13］ Luo SY, Chen S, Qin YD, et al. Urotensin-Ⅱ receptor antagonist SB-710411 protects rat heart against ischemia-reperfusion injuryvia RhoA/Rock pathway［J］. PLoS One, 2016, 11(1): 1-16.

［14］ Ban Y, Watanabe T, Suguro T, et al. Increased plasma urotensin-Ⅱ and carotid atherosclerosis are associated with vascular dementia［J］. J Atheroscler Thromb, 2009, 16(3): 179-187.

［15］ Papadopoulos P, Bousette N, Al-ramli W, et al. Targeted overexpression of the human urotensin receptor transgene in smooth muscle cells: effect of UT antagonism in ApoE knockout mice fed with Western diet［J］. Atherosclerosis, 2009, 204(2): 395-404.

［16］ Zhao J, Yu QX, Kong W, et al. The urotensinⅡ receptor antagonist, urantide, protects against atherosclerosis in rats［J］. Exp Ther Med,2013,5(6):1765-1769.

［17］ Lu LN, Yuan L, Liang BZh, et al. Effect of leonurine on expression of miR-1 in rats with myocardial fibrosis induced by isoproterenol［J］. Chinese Journal of Pathophysiology, 2018, 34(11): 1928-1934. (in Chinese)

卢丽娜, 袁露, 梁博志, 等. 益母草碱对异丙肾上腺素诱导大鼠心肌纤维化和miR-1表达的影响［J］. 中国病理生理杂志, 2018, 34(11): 1928-1934.

［18］ Wu L, Lü XT, Sun JH, et al. Antimyocardial fibrosis effect and mechanism of bailing capsule against viral myocarditis in mice［J］. Chinese Journal of Gerontology, 2018, 38(14): 3458-3461. (in Chinese)

吴岚, 吕欣桐, 孙景辉, 等. 百令胶囊对抗病毒性心肌炎小鼠抗心肌纤维化的作用及机制［J］. 中国老年学杂志, 2018, 38(14): 3458-3461.

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