Model Establishment And Mechanism Research Of Guinea Pigs' Hyperlipidemia And Early Atherosclerosis, And The Comparison With Rats

Objective The aim of this paper is to establish guinea pigs model of hyperlipidemia and early atherosclerosis, investigate the characteristics and mechanisms of guinea pigs' lipid metabolism disorders, and by the way of comparing the model with that of rats, illustrate the advantage of guinea pigs as model of hyperlipidemia and early atherosclerosis.Methods(1) Initial establishment of hyperlipidemia in guinea pigs: Diet containing 0.05% and 0.1% cholesterol were given to guinea pigs of model 1 and 2 groups, respectively. Levers of serum and hepatic lipids were detected at d₂₈.(2) Hyperlipidemia characteristics in guinea pigs: Diet containing 0.1% cholesterol was given to both of guinea pigs model group and rats model 1 group, and with 1% cholesterol to rats model 2 group for four weeks. Serum levels of lipids were detected with use of automatic biochemistry analyzer, serum CETP and Lpa were determined with enzyme immunosssay. Activitives and mRNA expression of ACAT and CYP7A1 in liver were detected by Enzymatic and RT-PCR analysis, respectively.(3) Hyperlipidemia-induced early atherosclerosis in guinea pigs: Diet containing 1% cholesterol was given to both guinea pigs and rats. Levels of lipids, CETP, Lp(a) and Ox-LDL in serum, and activities of ACAT in liver were detected with previous methods. Pathological changes of aortic early atherosclerosis were observed with HE staining, and the expression of PCNA, CD36 and VCAM-1 in aortic arch were quantified with both of immunohistochemistry and morphometry.Results(1) Hyperlipidemia model could be estabolished with diets containing 0.05% cholesterol intake, when diets cholesterol were added from 0.05% to 0.1%, concentration of serum TC were 1.96 and 3.18 times higher than that of control groups, serum LDL-C were 2.15 and 3.47 times higher than control groups, in addition, hepatic TC and TG concentration in both of the two model groups were increased significantly. The results demonstrated that guinea pigs could display dependency relationship with cholesterol dose-hyperlipidemia effect when diet cholesterol increased.(2) With intake of diet containing 0.1% choleaterol only for 3 weeks, serum TC, LDL-C and TG levers in guinea pigs increased by 4.04, 3.75 and 1.24 times, which indicated hyperlipidemia model were estabolished. And were kept up to the fourth week.Rats which were given the same diet to guinea pigs for 4 weeks had no changes in lipid levels, increase of lipid concentrations were only seen in rats model 2 groups given diet containing 1% cholesterol, but changes were much lower than that of guinea pigs. Compared with control, guinea pigs model group had a significant increase in serum CETP concentration and hepatic ACAT activities, but no changes on hepatic CYP7A1 activities. However, both of the two rats model showed no changes on CETP concentration and ACAT activities and mRNA expressin, and had a significant increase in hepatic CYP7A1 activities and mRNA expression.(3) With 1% cholesterol contained diets intake for 6 weeks, pathological changes of early atherosclerosis in guinea pigs were observed, which showed significant increases in intima-media thickness and intimal inflammatory cells infiltration. In addition, nearly 50 percent of model animals developed fatty streaks in aortic arch, with accumulation of lipids localized foam cells at high magnification (×400), monocytes and macrophages could be found in peripheral, without "collagenous fibre cap", obvious histiocytic necrosis, calcareous deposition, and thrombosis, Incidence rate of fatty streaks developed in guinea pigs fed on high choleaterol diets for 6 and 8 week was 4/9 and 6/15, respectively. However, rats which were given the same cholesterol containing diets for the same period (6 weeks and 8 weeks), no such pathological changes of early atherosclerosis were found, and none of the model groups developed fatty streak.Compared with control, serum lipid levels, CETP, LP (a) and Ox-LDL concentrations and hepatic ACAT activities increased significantly in guinea pigs fed on 1% cholesterol diets either for 6 weeks or 8 weeks. And expression of aorta PCNA, CD36, VCAM-1 in guinea pigs model group displayed significant higher than that of control, only serum CETP and Ox-LDL levels increased in rats given high lipid diets for 8 weeks.but changes were lower than that of guinea pigs.Conclusion(1) Guinea pigs were much more sensitive than rats to the diet cholesterol. They could develop hyperlipidemia when given low cholesterol (0.1% or even 0.05%) diets. With the same diets intake for the same period, rats could not develop hyperlipidemia model. Lipid levels increased with 1% cholesterol diets intake, but changes were much lower than that of guinea pigs.(2) When given an increased cholesterol (1%) diets for a relative longer period (6 weeks) guinea pigs could develop the pathological changes for early atherosclerosis. But the rats could not. Different changes of the key enzymies or protein which regulate the lipid metabolism and development of early atherosclerosis such as CETP, CYP7A1, ACAT, LP (a), CD36 and so on were closely related to the reasons why guinea pigs were easier than rats to develop hyperlipidemia and early athrosclerosis. And could explain the mechanisms for guieas pigs hyperlipidemia and early athrosclerosis.