Background

Statins are cholesterol lowering drugs that decrease the risk of cardiovascular events, but they are related with a few unfavorable symptoms in skeletal muscle including myopathy, and mild to moderate fatigue. Additionally, there has been discrepancies about the impacts of statins on brain and cognition. This study aimed to examine the impacts of two different statins, lipophilic simvastatin and hydrophilic rosuvastatin on cognitive functions in normal healthy rats. Simultaneously, we investigated the alterations of neurotropins and irisin levels in hippocampus and myokine levels in skeletal muscle.

Methods

The rats were dosed with 88 mg kg body weight⁻¹ day⁻¹ simvastatin (n = 8), 150 mg kg body weight⁻¹ day⁻¹ rosuvastatin (n = 8) or vehicle (n = 8) for 18 days via oral gavage. After that behavioral assessment was performed and hippocampus and skeletal muscle samples were taken for the analysis of neurotrophins and irisin levels.

Results

Locomotion and learning and memory functions were lower, but anxiety levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05). Hippocampal neurotrophins and irisin levels were lower, but skeletal muscle brain-derived neurotrophic factor (BDNF) and irisin levels were higher in the simvastatin and rosuvastatin groups than in the control group (P < 0.05).

Conclusion

These findings suggest that high dose simvastatin and rosuvastatin impair cognitive functions via decreasing BDNF, NGF and irisin levels in the hippocampus.

中文翻译：

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高剂量辛伐他汀和瑞舒伐他汀通过降低海马神经营养因子和鸢尾素损害健康大鼠的认知能力

背景

他汀类药物是降低胆固醇的药物，可降低心血管事件的风险，但它们与骨骼肌的一些不利症状有关，包括肌病和轻度至中度疲劳。此外，他汀类药物对大脑和认知的影响也存在差异。本研究旨在检查两种不同的他汀类药物，亲脂性辛伐他汀和亲水性瑞舒伐他汀对正常健康大鼠认知功能的影响。同时，我们研究了海马中神经激素和鸢尾素水平以及骨骼肌中肌因子水平的变化。

方法

通过口服给大鼠施用 88 mg kg 体重^-1天^-1辛伐他汀（n = 8）、150 mg kg 体重^-1天^-1瑞舒伐他汀（n = 8）或载体（n = 8），持续 18 天。灌胃。之后进行行为评估，并采集海马和骨骼肌样本用于分析神经营养因子和鸢尾素水平。

结果

与对照组相比，辛伐他汀组和瑞舒伐他汀组的运动和学习记忆功能较低，但焦虑水平较高（P < 0.05）。与对照组相比，辛伐他汀组和瑞舒伐他汀组海马神经营养因子和鸢尾素水平较低，但骨骼肌脑源性神经营养因子（BDNF）和鸢尾素水平较高（P < 0.05）。

结论

这些发现表明，高剂量辛伐他汀和瑞舒伐他汀通过降低海马中的 BDNF、NGF 和鸢尾素水平来损害认知功能。