Histological and ultrastructural changes in cross-striation muscle cells, under the influence of atorvastatin-reductase HMG-CoA inhibitor.

Miroslaw Lańcut, Barbara Jedrych, Marta Lis-Sochocka, Krystyna Czerny
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Abstract

The investigation was carried out on 15 Wistar rats--males weighing about 200 mg each. The animals were divided into three groups: one control group and two experimental groups, with five animals in each. In experimental group I the animals received emulsion of Atorvastatin in distilled water at the therapeutical dose of 80 mg/kg of body mass, by stomach tube for 6 weeks. In experimental group II the animals received atorvastatin at the maximal dose of 800 mg/kg of body mass. Skeletal muscles of experimental animals (rats) after 6 weeks' administration of atorvastatin in therapeutical and maximal dosages did not show any essential differences in comparison with the control group, when examined under light microscope. Degenerative changes were observed after Atorvastatin administration, when examined under electron microscope. These changes were dependent upon dosage and were directly proportional to dosage rate. Six-week administration of Atorvastatin in the therapeutical dose (80 mg/kg b. m.) produced invagination of the nuclear envelope into the cell nucleus, and within the cytoplasm, numerous vacuoles, some of which included the myelin structures, were evident. Atorvastatin administration in maximal dosage (800 mg/kg) under electron microscope examination, showed the following differences: the appearance of numerous vacuoles in the perinuclear spaces, and between myofibrils; dilation of mitochondria; disintegration of sacomers; fibrinosis within the intercellular spaces.

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阿托伐他汀还原酶HMG-CoA抑制剂对横纹肌细胞组织学和超微结构的影响。
这项研究是在15只Wistar大鼠身上进行的,雄性大鼠每只体重约200毫克。这些动物被分为三组:一个对照组和两个实验组,每组5只动物。实验1组动物以80 mg/kg体重的剂量,经胃管给予阿托伐他汀蒸馏水乳状液,持续6周。实验II组给予阿托伐他汀最大剂量为800 mg/kg体重。实验动物(大鼠)给予阿托伐他汀治疗剂量和最大剂量6周后,光镜下观察,与对照组相比,骨骼肌无明显差异。在电镜下观察,阿托伐他汀给药后观察到退行性改变。这些变化依赖于剂量,并与剂量率成正比。阿托伐他汀治疗剂量(80mg /kg / m)给药6周后,核膜内陷进入细胞核,细胞质内可见大量空泡,其中一些包括髓鞘结构。最大剂量(800 mg/kg)阿托伐他汀电镜检查显示:核周间隙和肌原纤维间出现大量空泡;线粒体扩张;聚体的分解;细胞间隙内的纤维纤维化。
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