低剂量他汀类药物联合葡萄柚对骨骼肌结构的影响及其对间充质干细胞可能的保护作用

A. A. Zeid, W. Baher, A. Hashem, B. M. Fahmy, Farah Ahmed Shafiek, M. Halem, N. A. Mohamed, R. A. Sakr
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引用次数: 1

摘要

背景:他汀类药物是治疗血脂异常的基础药物。它们通常耐受性良好,但可产生骨骼肌不良反应,从肌痛到横纹肌溶解。葡萄柚汁会增加辛伐他汀的血浆浓度,从而增加不良反应的风险。干细胞已被认为是开发创新治疗策略的潜在工具。目的:探讨小剂量他汀类药物联合葡萄柚对雌性大鼠肌肉结构的影响及其对骨髓间充质干细胞(bmscs)的保护作用。材料与方法:将25只成年雌性大鼠随机分为:I组(对照组,n=10),再分为:IA亚组(葡萄柚对照组);每日口服葡萄柚汁5 ml/kg, IB亚组(他汀类药物对照);Zocor®在自来水中每日口服20 mg/kg。II组(他汀+葡萄柚,n=5);5 ml/kg葡萄柚汁中加入20 mg/kg Zocor®,每日给予45天,III组(IMMSCs, n=5);他汀+葡萄柚与组II相同,在2次肌内注射BM-MSCs。IV组(IVMSCs, n=5);他汀+葡萄柚与组II相同,另外静脉注射两次BM-MSCs。测定不同时间间隔血浆肌酸激酶(CK)水平。末次给药后12 d处死,收集腓肠肌进行光镜和电镜观察。结果:两组对照均未见明显肌肉变化。II组t小管扩张,肌下间隙增宽,线粒体变性,肌原纤维解体,Z线丢失,大电子致密颗粒积聚。在第三和第四组,这些肌肉变化得到改善。结论:他汀类药物联合葡萄柚可引起肌肉超微结构的改变。注射骨髓间充质干细胞和静脉注射骨髓间充质干细胞均能改善这些变化,但注射骨髓间充质干细胞效果更好。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Effect of Low Dose Statin Combined with Grapefruit on Skeletal Muscle Structure and the Possible Protective Role of Mesenchymal Stem Cells
Background: Statins are the cornerstone of therapy for dyslipidemia. They are generally well tolerated but can produce skeletal muscle adverse reactions, ranging from myalgia to rhabdomyolysis. Grapefruit juice increases the plasma concentrations of simvastatin thus increasing the risk of adverse effects. Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. Objectives: To evaluate the effect of low dose statin combined with grapefruit on muscle structure and the possible protective role of Bone Marrow Mesenchymal Stem Cells (BM-MSCs) in female rats. Materials and Methods: Twenty five adult female rats were randomly divided into: Group I (control group, n=10) equally subdivided into: Subgroup IA (grapefruit control); 5 ml/kg oral grapefruit juice was given daily, Subgroup IB (statin control); 20 mg/kg oral Zocor® in tap water was given daily. Group II (statin + grapefruit, n=5); 20 mg/kg Zocor® in 5 ml/kg grapefruit juice was given daily for 45 days, Group III (IMMSCs, n=5); statin + grapefruit were given as in Group II, in addition to two intramuscular (IM) injections of BM-MSCs. Group IV (IVMSCs, n=5); statin + grapefruit were given as in Group II, in addition to two intravenous (IV) injections of BM-MSCs. Plasma level of Creatine Kinase (CK) was obtained at various intervals. All animals were sacrificed 12 days after the last dose, gastrocnemius muscles were collected and processed for light and electron microscopic study. Results: Both control subgroups showed unremarkable muscle changes. However, in Group II, dilated T-tubules, subsarcolemmal space widening, mitochondrial degeneration, disintegrated myofibrils, loss of Z lines and accumulation of large electron dense particles were detected. In Group III and IV these muscle changes were improved. Conclusion: Statin combined with grapefruit resulted in muscle ultrastructural changes. These changes were ameliorated with either IM and IV injection of MSCs, however IM injection showed better results.
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