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低剂量他汀类药物可减少高胆固醇血症兔的脉络膜损伤。

Low-dosage statins reduce choroidal damage in hypercholesterolemic rabbits.

机构信息

Institute for Ophthalmic Research, Ramón Castroviejo, Complutense University, Madrid, Spain.

出版信息

Acta Ophthalmol. 2011 Nov;89(7):660-9. doi: 10.1111/j.1755-3768.2009.01829.x. Epub 2010 Jan 8.

DOI:10.1111/j.1755-3768.2009.01829.x
PMID:20064114
Abstract

PURPOSE

To describe the ultrastructural changes in the choroid of long-term hypercholesterolemic rabbits after a low-dosage statin treatment and to evaluate some pleiotropic effects of these drugs on the morphology of endothelial cells (EC) and vascular smooth-muscle cells (VSMC).

METHODS

New Zealand rabbits were divided into three groups: G0, fed a standard diet; G1, fed a 0.5% cholesterol-enriched diet for 8 months and G2, fed a 0.5% cholesterol-enriched diet for 8 months plus administration of fluvastatin sodium or pravastatin sodium at a dose of 2 mg/Kg/day each. Eyes were processed for transmission-electron microscopy.

RESULTS

G1 had a lipid build-up at the suprachoroidea that compressed the vascular layers with the lumens of the vessels to the point of collapse in some instances. By contrast, G2 underwent a substantial decrease in suprachoroidal foam cells and of lipids in the vascular layers while the vascular lumens were normal. The preservation of cytoplasmic organelles, caveolar system and other ultrastructural features of EC and VSMC in G2 contrasted with the numerous signs of necrosis observed in G1. Bruch's membrane (BM) in G2 contained fewer lipids and more collagen than in G1.

CONCLUSION

Treatment with a low dosage of fluvastatin sodium or pravastatin sodium reduced the lipid build-up as well as the macrophages in the choroid and restored the vascular lumens of choroidal vessels independently of the cholesterol effect. The normal ultrastructural features of choroidal EC and VSMC in statin-treated animals suggest that the endothelial function is preserved and the ischaemia reduced.

摘要

目的

描述长期高胆固醇血症兔在低剂量他汀类药物治疗后脉络膜的超微结构变化,并评估这些药物对血管内皮细胞(EC)和血管平滑肌细胞(VSMC)形态的一些多效作用。

方法

将新西兰兔分为三组:G0 组,给予标准饮食;G1 组,给予 0.5%胆固醇强化饮食 8 个月;G2 组,给予 0.5%胆固醇强化饮食 8 个月,同时给予氟伐他汀钠或普伐他汀钠,剂量均为 2mg/Kg/天。对眼睛进行透射电镜处理。

结果

G1 组在脉络膜上方有脂质堆积,血管层的血管腔受压,导致血管腔在某些情况下塌陷。相比之下,G2 组脉络膜泡沫细胞和血管层脂质大量减少,而血管腔正常。G2 组 EC 和 VSMC 的细胞质细胞器、小窝系统和其他超微结构特征得以保存,而 G1 组则存在大量坏死迹象。G2 组的 Bruch 膜(BM)中含有的脂质比 G1 组少,而胶原比 G1 组多。

结论

用低剂量的氟伐他汀钠或普伐他汀钠治疗可减少脉络膜中的脂质堆积和巨噬细胞,并恢复脉络膜血管的血管腔,而与胆固醇效应无关。他汀类药物治疗动物脉络膜 EC 和 VSMC 的正常超微结构特征表明内皮功能得到保存,缺血减少。

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