Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis
Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis
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DOI：
10.3389/fphys.2019.00267
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发表时间：
2019-03-22
影响因子：
4
通讯作者：
Deng, Wenhao
中科院分区：
文献类型：
--
作者：
Li, Sha;Li, Shuren;Deng, Wenhao
目的：心室重构被认为是心力衰竭的基础，并参与心肌纤维化。本研究旨在评估培哚普利和半乳凝素-3抑制剂（改性柑橘果胶，MCP）对缺血性心力衰竭兔心室重构和心肌纤维化的影响。方法：将兔分为假手术组、心力衰竭（模型）组、MCP组和培哚普利组。结扎家兔冠状动脉前降支建立缺血性心力衰竭模型。然后，家兔口服MCP、培哚普利或生理盐水（均为2 ml/kg/d），持续4周。假手术组动物仅接受心内直视手术，未进行进一步治疗。4周后，超声检测心功能，实时荧光定量PCR和Western-Blot检测心肌Gal-3、I型胶原和III型胶原的基因和蛋白表达，ELISA检测血清Gal-3，H&E和Masson染色评价梗死区纤维化。在模型动物中，心肌Gal-3，I型胶原和III型胶原基因和蛋白表达水平与对照值相比增加，以及血清Gal-3量。培哚普利和MCP治疗可显著减轻上述影响，治疗组间无显著差异。病理分析表明，与模型动物相比，治疗与MCP或培哚普利导致相对整齐排列的心肌细胞在梗死zone.Conclusion：培哚普利和半乳糖凝集素-3抑制剂MCP-10改善缺血性心力衰竭兔，下调Gal-3和减少心肌纤维化。
Objective: Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure.Methods: Rabbits were divided into sham, heart failure (model), MCP, and perindopril groups, respectively. A rabbit model of ischemic heart failure was established by ligating the anterior descending coronary artery. Then, the rabbits were orally administered MCP, perindopril, or saline (all at 2 ml/kg/d) for 4 weeks. Sham animals only underwent open heart surgery without further treatment. After 4 weeks, cardiac function was examined by ultrasound, and myocardial Gal-3, collagen type I, and collagen type III expression was assessed, at the gene and protein levels, by real-time PCR and Western-Blot, respectively; serum Gal-3 was detected by ELISA, and fibrosis in the infarct zone was evaluated by H&E and Masson staining.Results: In model animals, myocardial Gal-3, collagen type I, and collagen type III gene and protein expression levels were increased compared with control values, as well as serum Gal-3 amounts. Treatment with perindopril and MCP significantly alleviated the above effects, with no significant differences between the treatment groups. Pathological analyses showed that compared with model animals, treatment with MCP or perindopril resulted in relatively neatly arranged myocardial cells in the infarct zone, with significantly decreased fibrosis.Conclusion: Perindopril and the galectin-3 inhibitor MCP comparably improve ischemic heart failure in rabbits, by downregulating Gal-3 and reducing myocardial fibrosis.