Development of a novel method for analyzing murine lipoprotein profile and application for an experimental model of lipoprotein glomerulopathy

点击翻译按钮获取中文摘要

1. Establishment of capillary isotachophoresis (cITP) method for murine lipoprotein profile analysis.Pooled plasma which was collected from apoE deficiency mice was demarcated by ultracentrifugation in specific gravity of each lipoprotein, and detailed lipoprotein profiles of centrifuged plasma were measured by cITP. As a result, we revealed that peak 1-3, peak 4, peak 5, and peak 6-8 corresponded to HDL, CM/VLDL, VLDL/IDL, and VLDL/LDL respectively. Therefore, It is demonstrated that cITP method is useful to analyze murine plasma lipoprotein profiles.2. A comparison of lipoprotein profile by cITP and histology of apoE deficiency mice administered by recombinant apoEs.We introduced apos E2, E3, and E4, and ApoE-Sendai inducted adenovirus vector to apoE deficiency mice, and examined their plasma lipoprotein profile by cITP and renal histology. In lipoprotein analysis, mice introduced by ApoE-Sendai showed rise of peak 6, whereas mice by other apoEs showed rise of peak 7. In renal histology, changes similar to lipoprotein glomerulopathy (LPG) were demonstrated in 76.5% of ApoE-Sendai introduced-mice, while a little change was appeared in other mice. (ANOVA_p<0.001)3. Severity of LPG like change in ApoE-Sendai introduced mice.Histlogical findings of ApoE-Sendai introduced mice were categorized into three grades; mild (46.1%), moderate (25.0%), and severe (5.8%). Mild group displayed only mesangial lipoprotein deposition and vacuolation; moderate group, a few lipoprotein thrombus, and severe group, many lipoprotein thrombi.) In several glomeruli, lipoprotein deposits in mesangial matrix were going to migrate into the capillary. It is suggested that lipoprotein may move from mesangial matrix to capillary lumen according to the progression of LPG.These results revealed that cITP method was available for analysis of murine plasma lipoprotein profile, and that abnormal electrophoretic VLDL/LDL, which is demarcated peak 6, is related to the development of LPG.