辛伐他汀对铜和高胆固醇阿尔茨海默病家兔海马淀粉样肽前蛋白mRNA表达的影响

Effect of simvastatin on hippocampus APP mRNA expression in copper-cholesterol AD rabbit model

目的研究辛伐他汀对铜和高胆固醇诱导的阿尔茨海默病(AD)家兔海马淀粉样肽前蛋白(APP)mRNA表达的影响。方法采用Sparks方法复制铜和高胆固醇诱导的AD家兔模型。辛伐他汀(5mg·kg-1·d-1)灌胃3w,高效液相色谱法(HPLC)检测家兔海马胆固醇含量,实时定量RT-PCR法检测海马APP mRNA表达水平。分析海马胆固醇含量与海马APP mRNA表达的相关性。结果模型组海马胆固醇含量及APP mRNA表达水平显著高于正常组(P<0.05)。辛伐他汀组海马胆固醇含量及APP mRNA表达水平显著低于模型组(P<0.05);与正常组相无显著差别(P>0.05)。海马APP mRNA表达水平与海马胆固醇含量呈正相关(r=0.58,P<0.05)。结论辛伐他汀可通过降低海马胆固醇含量减少APP转录,这可能是辛伐他汀降低AD发病的机制。

Objective To study the effect of simvastatin on hippocampus APP mRNA expression in copper-cholesterol AD rabbits.Methods The copper-cholesterol rabbit AD model was replicated referring to Sparks method.Simvastatin was used to treat the rabbits by gastric perfusion at a dose of 5 mg·kg-1·d-1 for 3 weeks. High performance liquid chromatography（HPLC） was used to detect cholesterol levels in rabbit hippocampus,RT-PCR to detect the expression of APP mRNA levels in hippocampus.The correlation between cholesterol content and APP mRNA expression of the rabbit hippocampus was analyzed.Results The cholesterol content and the expression of APP mRNA levels were significantly increased in model group,the difference was significant compared with normal group（P0.05）.Hippocampus cholesterol content and APP mRNA expression was significantly decreased in simvastatin group,there was significant difference compared with model group（P0.05）;no significant difference compared with normal group（P0.05）.The level of the hippocampus cholesterol and hippocampus APP mRNA expression was positively correlated（r=0.58,P0.05）.Conclusions Simvastatin can reduce APP transcription of the hippocampus by reducing cholesterol levels,which may be the mechanism of simvastatin reducing AD incidence.