Shimoda Tomoko, Ishihata Akira, Aita Tomomi, Kaga Mikako, Ito Tsunekata, Ohwada Kazuo, Tomoike Hitonobu, Katano Yumi
Department of Physiology 1, Laboratory Animal Center, Yamagata University School of Medicine, Yamagata, Japan.
Clin Exp Pharmacol Physiol. 2006 Mar;33(3):221-6. doi: 10.1111/j.1440-1681.2006.04349.x.
We have recently segregated a new line of rabbit, named TGH, with severely high levels of plasma triglyceride and cholesterol. The aim of the present study was to investigate the progression of atherosclerosis and haemodynamic parameters in TGH rabbits. 2. Japanese white (JW) and TGH rabbits (24-27 months old) were anaesthetized with ketamine and xylazine. Plasma concentrations of triglyceride were 63.1 8.0 and 446.0 35.2 mg/dL in JW and TGH rabbits, respectively. Blood pressure was measured by a catheter implanted in the femoral artery. Histological examinations were performed using haematoxylin-eosin and elastica-Masson trichrome staining to detect atherosclerotic lesions. 3. The JW rabbits had no atherosclerotic lesions. In TGH rabbits, severe atherosclerotic lesions were observed throughout the aorta, especially in the aortic arch. Basal femoral arterial pressure was not significantly different between JW and TGH rabbits. However, the basal pulse pressure in TGH rabbits (48.3 4.5 mmHg) was significantly greater than that of JW rabbits (28.0 5.6 mmHg). Intravenous infusion of N(G)-nitro-L-arginine methyl ester (L-NAME; 26.9 mg/kg) increased the blood pressure of TGH and JW rabbits. There was no significant difference in the response to L-NAME between the two rabbit strains. 4. The present study shows that severe atherosclerotic changes develop in TGH rabbits and suggests that the hyperlipidaemia combined with hypercholesterolaemia and hypertriglyceridaemia is an important factor for promoting atherosclerosis in TGH rabbits. The greater pulse pressure in TGH rabbits may be due to the increased vascular stiffness with atherosclerosis. 5. This newly developed TGH rabbit line of heritable hypertriglyceridaemia with hypercholesterolaemia will become a useful animal model for studies on the role of hyperlipidaemia in the progression of atherosclerosis and in many atherosclerosis-related diseases.
我们最近分离出了一种新的兔种系，名为TGH，其血浆甘油三酯和胆固醇水平严重偏高。本研究的目的是调查TGH兔动脉粥样硬化的进展情况和血流动力学参数。2. 日本白兔（JW）和TGH兔（24 - 27月龄）用氯胺酮和赛拉嗪麻醉。JW兔和TGH兔的血浆甘油三酯浓度分别为63.1±8.0和446.0±35.2mg/dL。通过植入股动脉的导管测量血压。使用苏木精 - 伊红和弹性蛋白 - 马森三色染色进行组织学检查以检测动脉粥样硬化病变。3. JW兔没有动脉粥样硬化病变。在TGH兔中，整个主动脉都观察到严重的动脉粥样硬化病变，尤其是在主动脉弓。JW兔和TGH兔之间的基础血压没有显著差异。然而，TGH兔的基础脉压（48.3±4.5mmHg）显著高于JW兔（28.0±5.6mmHg）。静脉注射N(G)-硝基-L-精氨酸甲酯（L-NAME；26.9mg/kg）可使TGH兔和JW兔的血压升高。两种兔种系对L-NAME的反应没有显著差异。4. 本研究表明TGH兔出现了严重的动脉粥样硬化变化，并表明高胆固醇血症和高甘油三酯血症合并的高脂血症是促进TGH兔动脉粥样硬化的重要因素。TGH兔中较大的脉压可能是由于动脉粥样硬化导致血管硬度增加。5. 这种新培育的具有高胆固醇血症和遗传性高甘油三酯血症的TGH兔种系将成为研究高脂血症在动脉粥样硬化进展以及许多与动脉粥样硬化相关疾病中作用的有用动物模型。
