Aim To explore the methods of successful estahlishment of experimental guinea pig atherosclerosis model . which has the typical pathological f'eatures of' atherosclerosis . and elucidate the development mechanisms of' atherosclerosis with comparison with rats , in order to clarify the advantages of this new guinea pig atherosclerosis model. Methods The establishment of' experimental guinea pig atherosclerosis model was induced hy high-cholesterol diets. Both the guinea pigs and rats were randomlv divided into three groups ( 10 per group ) : normal control group , guinea pig model 1 group ( 0. 5 percent cholesterol and 10 percent lard) and guinea pig model 2(1 percent cholesterol and 10 percent lard) . the study lasted 10 weeks for the estahlishment of atherosclerosis. Lipids deposition in arterial wall was stained with Sudan Ⅳ ; Masson ' s trichrome staining was performed to observe the collagen deposition in atherosclerostic plaques ; the level of' serum hs-CRP was detected using Enzymelinked immunosorbent assay ( ELISA ) ; the relative expressions of PPARα mRNA in liver were detected hv real -time PCR ; the protein expression of ICAM-1 in aortic wall of atherosclerosis were evaluated hy immunohistochemistry. Results Lipid plaques in arterial wall and collagen fihers of intima and media were mcreased in 80 percent of model 1 group and 70 percent of model 2 group. In comparison with control group , the plaque area ％ , collagen fiher area％ . intimal area％ and intimal area/media area ratio were significantly increased . No such significant diff'erences were ohserved in rat fed with the same high -cholesterol diets ; the serum hs-CRP increased and the relative expressions of PPARα mRNA and aortal ICAM-1 adhesion molecules protein expression occured up -regulation in guinea pigs . Conclusions (Guinea pigs develop typical atherosclerosis with hypercholesterolemic diets for 10 weeks and the mechanism might be related to vascular inflammation and the species specificity of PPARα is much more similar to guinea pigs. The guinea pig models have an advantage over rat ones .%目的 建立豚鼠动脉粥样硬化模型,并对形成机制进行探讨,同时与大鼠模型进行比较,阐明豚鼠模型特点和优势.方法 应用高脂饲料诱导法建立动脉粥样硬化模型,将豚鼠和大鼠分别随机分为正常对照组(饲常规饲料)、模型1组(质量分数分别为0.005的胆固醇、0.1的猪油、0.895基础饲料)和模型2组(质量分数分别为0.01的胆固醇、0.1的猪油、0.89的基础饲料),每组10只,连续饲养10周,苏丹Ⅳ染色观察主动脉壁斑块病灶面积,Masson染色观察动脉内膜胶原纤维的变化.酶联免疫分析法测定血清hs-CRP浓度,实时荧光定量法检测肝脏PPARα相对表达,免疫组化技术检测血管内膜ICAM-1蛋白表达的变化.结果 豚鼠模型1组比例为0.8的动物,模型2组比例为0.7的动物的主动脉壁出现较多脂质斑块,内膜和中膜胶原纤维明显增生,与对照组比较,斑块面积和胶原纤维面积百分比均明显增加,肝脏PPARα表达不变,大鼠两个模型组的主动脉壁未出现明显的阳性染色斑块,胶原纤维增生不明显,肝脏PPARα表达明显下调.豚鼠血清hs-CRP浓度升高,动脉内膜ICAM-1蛋白表达上调.结论 经高胆固醇饲料诱导10周后,豚鼠两个模型组均可形成典型动脉粥样硬化病变,病变形成可能与血管损伤性炎症反应有关,且其PPARα种属特异性较大鼠更接近人类,豚鼠模型有明显优势.
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