高胆固醇饮食对兔脑血流量和β-淀粉样蛋白1-42水平的影响

Alteration of cerebral blood flow and amyloid β-protein 1-42 deposition in rabbits fed with high cholesterol diet

目的探讨高胆固醇饮食对兔脑血流量(CBF)和脑组织β-淀粉样蛋白1-42(Aβ1-42)水平的影响,并分析血清TC、CBF及Aβ1-42水平的相关性。方法将12只日本大白兔采用随机数字表法分为高胆固醇组和常规饮食组各6只,高胆固醇组以2%胆固醇饮食喂养,常规饮食组以常规基础饮食喂养,12周后取耳缘静脉血测定血脂浓度,采用MRI动脉自旋标记序列测量皮质和海马CBF;随后处死取脑分离皮质、海马,采用ELISA法检测其Aβ1-42水平;比较两组兔脑皮质、海马CBF及Aβ1-42水平。采用Person相关分析血清TC水平、CBF与Aβ1-42水平的相关性。结果高胆固醇组兔脑皮质、海马CBF均明显低于常规饮食组,兔脑皮质、海马Aβ1-42水平均明显高于常规饮食组,差异均有统计学意义(均P<0.05)。血清TC与皮质、海马Aβ1-42水平均呈正相关(r=0.774和0.649,均P<0.05);血清TC与皮质、海马CBF均呈负相关(r=-0.845和-0.783,均P<0.01);皮质、海马Aβ1-42水平与CBF均呈负相关(r=-0.637和-0.602,均P<0.05)。结论高胆固醇饮食能引起兔脑皮质、海马CBF的减少和Aβ1-42水平的升高,继发于高血脂的低血流灌注可能参与并促进了Aβ1-42的异常沉积。

Objective To investigate the alteration of cerebral blood flow （CBF） and amyloid β-protein 1-42（Aβ1-42）deposition in rabbits fed with high cholesterol diet. Methods Twelve Japanese white rabbits were divided into2 groups with6 ineach group： rabbits in group RD were fed with routine diet and those in group CD were fed with high cholesterol diet containing2% cholesterol for 12 weeks. Serum lipid concentrations were analyzed. 3D MR artery spin labeling（3D-ASL） were performed byusinga 3T MRI scanner with an 8 channel rabbit coil, the parameter map of CBF was created and blood flow was measured bythe function tool perfusion software. The levels ofAβ1-42 protein in cortical, hippocampal tissues were measured by ELISA. Thedifferences of CBF andAβ1-42 between two groups were analyzed, and the association among total cholesterol（TC）, CBF andAβ1-42 was also examined with Pearson＇s correlation analysis. Results The CBF in cortical, hippocampal tissues of CD groupboth were lower than those of RD group（both P〈0.05）. The levels ofAβ1-42 protein in cortical, hippocampal tissues of CDgroup were higher than those of RD group（both P〈 0.05）. There were significant correlations between the serum TC levels andthe levels ofAβ1-42 in the cortex（r=0.774, P〈0.05） and hippocampus（r=0.649, P〈0.05 ）, between the TC levels and the CBF inthe cortex（r=-0.845, P〈0.01） and hippocampus（r=-0.783, P〈0.01）, between the CBF and theAβ1-42 level in the cortex（r=-0.637, P〈0.05） and hippocampus（r=-0.602, P〈0.05）. Conclusion This study indicates that high cholesterol diets may leadto low CBF and exacerbate the deposition ofAβ1-42 in cerebral tissue. The decreased CBF secondary to hyperlipidemia maybe associated with the abnormal deposition ofAβ1-42.