地尔硫䓬可降低异丙肾上腺素诱导的自由活动大鼠体内红细胞中 ATP 的死亡和分解。

Diltiazem reduces mortality and breakdown of ATP in red blood cell induced by isoproterenol in a freely moving rat model in vivo.

机构信息

Pharmacokinetics and Metabolism Laboratory, College of Pharmacy and Department of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.

Department of Pathology, Faculty of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, 5788 University Ave., Halifax, NS B3H 1V8, Canada.

出版信息

Metabolites. 2014 Sep 11;4(3):775-89. doi: 10.3390/metabo4030775.

DOI:10.3390/metabo4030775

PMID:25215514

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4192692/

Abstract

The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ) against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses. One hour after the last injection, a single dose of isoproterenol (30 mg/kg) was injected sc to each rat. Blood samples were collected serially for 6 h for measurement of adenine nucleotides (ATP, ADP and AMP) in red blood cell (RBC) by a validated HPLC. The study has shown isoproterenol induced 50% mortality and also increased RBC concentrations of AMP from 0.04 ± 0.02 to 0.29 ± 0.21 mM at the end of the experiment (p < 0.05). Treatment with 10 mg/kg of DTZ reduced mortality from 50% to <20% and attenuated the increase of RBC concentrations of AMP from +0.25 ± 0.22 in the control rats to +0.072 ± 0.092 mM (p < 0.05). The study concluded that 10 mg/kg of DTZ reduced mortality and breakdown of ATP induced by isoproterenol in rats.

摘要

钙通道阻滞剂在预防心脏病发作和中风方面的心血管益处尚未得到确凿支持。我们使用体内自由活动的大鼠模型研究了地尔硫䓬（DTZ）对异丙肾上腺素诱导损伤的可能心血管保护作用。SD 大鼠皮下（sc）注射 5 或 10mg/kg 的 DTZ，或生理盐水作为对照，每日两次，共 5 次。最后一次注射后 1 小时，每只大鼠 sc 注射单剂量异丙肾上腺素（30mg/kg）。连续采集 6 小时的血清样本，通过验证的 HPLC 测量红细胞（RBC）中的腺嘌呤核苷酸（ATP、ADP 和 AMP）。该研究表明，异丙肾上腺素诱导 50%的死亡率，并在实验结束时将 RBC 中 AMP 的浓度从 0.04±0.02 增加到 0.29±0.21mM（p<0.05）。用 10mg/kg 的 DTZ 治疗将死亡率从 50%降低到<20%，并减轻了对照大鼠中 RBC 中 AMP 浓度的增加，从+0.25±0.22 增加到+0.072±0.092mM（p<0.05）。该研究得出结论，10mg/kg 的 DTZ 降低了异丙肾上腺素诱导的大鼠死亡率和 ATP 分解。