匹伐他汀诱导的胆固醇缺乏会升高大鼠体内与他汀类药物相关不良反应有关的血清生物标志物水平。
Pitavastatin-induced cholesterol deficiency elevates serum biomarkers associated with statin-related adverse effects in rats.
作者信息
Abolhasani Sakhavat, Ahmadi Yasin, Saadati Hossein Mozafar
机构信息
Department of Basic Sciences and Health, Sarab Faculty of Medical Sciences, Sarab East Azerbaijan, Iran.
Department of Medical Laboratory Science, Komar University of Sciences and Technology, Sulaymaniyah, Kurdistan Region, Iraq.
出版信息
Cardiovasc Endocrinol Metab. 2025 Mar 7;14(2):e00326. doi: 10.1097/XCE.0000000000000326. eCollection 2025 Jun.
BACKGROUND
Statins are prescribed to manage hypercholesterolemia. While effective, these medications are associated with adverse effects, particularly myopathy. Cholesterol is essential for muscle function, and its depletion - especially by lipophilic statins - may contribute to muscle damage. Pitavastatin mainly targets hepatic cholesterol synthesis with minimal direct effect on muscle tissue. This study investigates the impact of pitavastatin-induced cholesterol depletion on skeletal muscle.
METHODS
Male Sprague-Dawley rats were divided into three groups: control ( = 10), pitavastatin-treated on a normal diet (ND, = 10), and pitavastatin-treated on a high-cholesterol diet (HCD, = 10). Pitavastatin (15 mg/kg/day) was administered orally for 6 weeks. Serum lipid profile, hepatic injury markers (alanine aminotransferase, aspartate aminotransferase), muscle damage markers (creatine phosphokinase), and bone metabolism indicators (alkaline phosphatase, calcium, phosphate, or magnesium) were analyzed.
RESULTS
Pitavastatin significantly reduced total cholesterol and low-density lipoprotein cholesterol in both ND and HCD groups ( < 0.05) without affecting triglycerides, high-density lipoprotein cholesterol, or very-low-density lipoprotein. The ND group showed significant elevations in alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase compared to the control and HCD groups ( < 0.05), suggesting cholesterol depletion contributes to hepatic and muscle damage. The HCD group exhibited reduced elevations in these markers, indicating a protective role of dietary cholesterol. No significant differences were observed in alkaline phosphatase, calcium, phosphate, or magnesium. Bivariate correlation analysis showed an inverse association between total cholesterol and liver enzyme markers.
CONCLUSION
Pitavastatin-induced cholesterol depletion increased hepatic and muscle damage markers. Dietary cholesterol may mitigate these effects, highlighting the importance of cholesterol homeostasis in statin therapy.
背景
他汀类药物用于治疗高胆固醇血症。虽然这些药物有效，但会产生不良反应，尤其是肌病。胆固醇对肌肉功能至关重要，其消耗——尤其是亲脂性他汀类药物导致的消耗——可能会导致肌肉损伤。匹伐他汀主要作用于肝脏胆固醇合成，对肌肉组织的直接影响最小。本研究调查了匹伐他汀诱导的胆固醇消耗对骨骼肌的影响。
方法
将雄性Sprague-Dawley大鼠分为三组：对照组（n = 10）、正常饮食匹伐他汀治疗组（ND，n = 10）和高胆固醇饮食匹伐他汀治疗组（HCD，n = 10）。口服给予匹伐他汀（15 mg/kg/天），持续6周。分析血清脂质谱、肝损伤标志物（丙氨酸转氨酶、天冬氨酸转氨酶）、肌肉损伤标志物（肌酸磷酸激酶）和骨代谢指标（碱性磷酸酶、钙、磷或镁）。
结果
匹伐他汀显著降低了ND组和HCD组的总胆固醇和低密度脂蛋白胆固醇（P < 0.05），而不影响甘油三酯、高密度脂蛋白胆固醇或极低密度脂蛋白。与对照组和HCD组相比，ND组的丙氨酸转氨酶、天冬氨酸转氨酶和肌酸磷酸激酶显著升高（P < 0.05），表明胆固醇消耗会导致肝脏和肌肉损伤。HCD组这些标志物的升高有所降低，表明饮食中的胆固醇具有保护作用。碱性磷酸酶、钙、磷或镁方面未观察到显著差异。双变量相关性分析显示总胆固醇与肝酶标志物之间呈负相关。
结论
匹伐他汀诱导的胆固醇消耗增加了肝脏和肌肉损伤标志物。饮食中的胆固醇可能会减轻这些影响，突出了胆固醇稳态在他汀类药物治疗中的重要性。
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