A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats.
A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats.
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DOI：
10.5551/jat.40956
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发表时间：
2018-05-01
影响因子：
4.4
通讯作者：
Oka H
中科院分区：
文献类型：
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作者：
Watanabe S;Kumazaki S;Kusunoki K;Inoue T;Maeda Y;Usui S;Shinohata R;Ohtsuki T;Hirohata S;Kusachi S;Kitamori K;Mori M;Yamori Y;Oka H
目的：无论代谢综合征的危险因素如何，非酒精性脂肪性肝炎（NASH）都会增加心血管风险。然而，NASH和血管疾病之间的中介因素仍然是未知的，因为还没有建立合适的动物模型。易卒中（SP）的自发性高血压大鼠SHRSP 5/Dmcr在喂食高脂肪和高胆固醇（HFC）饮食时同时发生高血压、肠系膜动脉中急性动脉脂质沉积和NASH。我们研究了SHRSP 5/Dmcr在NASH中的表达是否与心血管功能障碍有关。方法：将Wister京都和SHRSP 5/Dmcr大鼠分为4组，每组5只，分别饲喂SP和HFC饲料。喂食HFC或SP饲料8周后，评价葡萄糖和胰岛素抵抗、超声心动图、血液生化、组织病理学染色和主动脉内皮功能。结果如下：我们证明，用HFC饮食喂养的SHRSP 5/Dmcr大鼠表现出由心脏纤维化、内皮功能障碍和左心室舒张功能障碍引起的心脏和血管功能障碍，与NASH和高血压相关。这些心脏和血管功能障碍加重，与高血压、葡萄糖代谢紊乱和/或肥胖无关。结论：SHRSP 5/Dmcr大鼠是研究NASH与心、血管功能障碍相互作用的理想动物模型。
Aim: Non-alcoholic steatohepatitis (NASH) increases cardiovascular risk regardless of risk factors in metabolic syndrome. However, the intermediary factors between NASH and vascular disease are still unknown because a suitable animal model has never been established. The stroke-prone (SP) spontaneously hypertensive rat, SHRSP5/Dmcr, simultaneously develops hypertension, acute arterial lipid deposits in mesenteric arteries, and NASH when feed with a high-fat and high-cholesterol (HFC) diet. We investigated whether SHRSP5/Dmcr affected with NASH aggravates the cardiac or vascular dysfunction. Method: Wister Kyoto and SHRSP5/Dmcr rats were divided into 4 groups of 5 rats each, and fed with a SP or HFC diet. After 8 weeks of HFC or SP diet feeding, glucose and insulin resistance, echocardiography, blood biochemistry, histopathological staining, and endothelial function in aorta were evaluated. Results: We demonstrate that SHRSP5/Dmcr rats fed with a HFC diet presented with cardiac and vascular dysfunction caused by cardiac fibrosis, endothelial dysfunction, and left ventricular diastolic dysfunction, in association with NASH and hypertension. These cardiac and vascular dysfunctions were aggravated and not associated with the presence of hypertension, glucose metabolism disorder, and/or obesity. Conclusions: SHRSP5/Dmcr rats may be a suitable animal model for elucidating the organ interaction between NASH and cardiac or vascular dysfunction.