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载辅酶Q10脂质体对急性实验性心肌梗死家兔心肌的保护作用。

Protective effect of coenzyme Q10-loaded liposomes on the myocardium in rabbits with an acute experimental myocardial infarction.

作者信息

Verma Daya D, Hartner William C, Thakkar Vineet, Levchenko Tatyana S, Torchilin Vladimir P

机构信息

Center for Pharmaceutical Biotechnology and Nanomedicine, Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.

出版信息

Pharm Res. 2007 Nov;24(11):2131-7. doi: 10.1007/s11095-007-9334-0. Epub 2007 Jul 27.

Abstract

PURPOSE

We assessed whether the infusion of Coenzyme Q10-loaded liposomes (CoQ10-L) in rabbits with an experimental myocardial infarction can result in increased intracellular delivery of CoQ10 and thus limit the fraction of the irreversibly damaged myocardium.

METHODS

CoQ10-L, empty liposomes (EL), or Krebs-Henseleit (KH) buffer were administered by intracoronary infusion, followed by 30 min of occlusion and 3 h of reperfusion. Unisperse Blue dye was used to demarcate the net size of the occlusion-induced ischemic zone ("area at risk") while nitroblue tetrazolium staining was used to detect the final fraction of the irreversibly damaged myocardium within the total area at risk.

RESULTS

The total size of the area at risk in all experimental animals was approx. 20% wt. of the left ventricle (LV). The final irreversible damage in CoQ10-L-treated animals was only ca. 30% of the total area at risk as compared with ca. 60% in the group treated with EL (p < 0.006) and ca. 70% in the KH buffer-treated group (p < 0.001).

CONCLUSIONS

CoQ10-L effectively protected the ischemic heart muscle by enhancing the intracellular delivery of CoQ10 in hypoxic cardiocytes in rabbits with an experimental myocardial infarction as evidenced by a significantly decreased fraction of the irreversibly damaged heart within the total area at risk. CoQ10-L may provide an effective exogenous source of the CoQ10 in vivo to protect ischemic cells.

摘要

目的

我们评估了在患有实验性心肌梗死的兔子中输注负载辅酶Q10的脂质体(CoQ10-L)是否能增加辅酶Q10的细胞内递送,从而限制不可逆损伤心肌的比例。

方法

通过冠状动脉内输注给予CoQ10-L、空脂质体(EL)或克雷布斯-亨泽莱特(KH)缓冲液,随后进行30分钟的闭塞和3小时的再灌注。使用单分散蓝色染料划定闭塞诱导的缺血区(“危险区域”)的净大小,同时使用硝基蓝四氮唑染色检测危险区域总面积内不可逆损伤心肌的最终比例。

结果

所有实验动物的危险区域总面积约为左心室(LV)重量的20%。与EL处理组的约60%和KH缓冲液处理组的约70%相比,CoQ10-L处理动物的最终不可逆损伤仅约为危险区域总面积的30%(p<0.006)和(p<0.001)。

结论

CoQ10-L通过增强实验性心肌梗死兔子缺氧心肌细胞中辅酶Q10的细胞内递送,有效保护了缺血心肌,这表现为危险区域总面积内不可逆损伤心脏的比例显著降低。CoQ10-L可能提供一种有效的体内辅酶Q10外源性来源以保护缺血细胞。

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