Li M, Wen C, Whitworth J A
Department of Medicine, St. George Hospital, Kogarah, New South Wales, Australia.
Am J Hypertens. 1997 Mar;10(3):332-6. doi: 10.1016/s0895-7061(96)00318-4.
To determine whether the immune Fab fragment of digoxin antibody (digibind) attenuates established corticotropin (ACTH) hypertension, rats were given ACTH sham control (0.1 mL normal saline, twice daily, subcutaneously, n = 18) or ACTH treatment (2.5 microg/kg in 0.1 mL normal saline, twice daily, subcutaneously; n = 27) for 10 days. Acute hemodynamic effects of digibind (30 mg/kg, intravenous bolus injection) were examined after 10 days of sham control or ACTH treatment. Rats were divided into 7 groups: digibind (30 mg/kg, in 1 mL 0.9% NaCl intravenous bolus injection) plus sham (n = 6) or ACTH (n = 8), sham digibind (1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 7), digibind vehicle (sorbitol 1.8 mg in 1 mL 0.9% NaCl, intravenous bolus) plus sham (n = 6), preimmune sheep IgG (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus sham (n = 6) or ACTH (n = 6) and preimmune sheep IgG (Fab)2 fragment (30 mg/kg in 1 mL 0.9% NaCl intravenous bolus) plus ACTH (n = 6). ACTH increased systolic blood pressure (SBP) from 118 +/- 2 to 132 +/- 3 mm Hg on treatment day 10. BP was unchanged in sham treated rats. The acute administration of digibind decreased MAP (-14 +/- 3 mm Hg, P <.001) in ACTH hypertensive rats, but not in ACTH sham control normotensive rats (+2 +/- 3 mm Hg). Blood pressure reached a minimum after 14 +/- 3 min and the effect lasted more than 30 min. No significant change of blood pressure was found in ACTH treated rats receiving sham (0.9% NaCl) digibind injection (+2 +/- 2 mm Hg). However, both preimmune sheep IgG and IgG (Fab)2 fragment caused a decrease of blood pressure in both sham or ACTH treated rats. Although these data that digibind decreases BP in ACTH but not sham treated rats are consistent with the notion that digitalis-like substances may play a role in ACTH induced hypertension, the evidence that both preimmune sheep IgG and IgG (Fab)2 fragments also decreased blood pressure in rats suggests caution in interpretation of studies that employ digibind preparations.
为了确定地高辛抗体的免疫Fab片段（地高辛抗体片段）是否能减轻已形成的促肾上腺皮质激素（ACTH）性高血压，将大鼠分为ACTH假手术对照组（0.1 mL生理盐水，每日两次，皮下注射，n = 18）或ACTH治疗组（2.5 μg/kg溶于0.1 mL生理盐水中，每日两次，皮下注射；n = 27），持续10天。在假手术对照组或ACTH治疗10天后，检测地高辛抗体片段（30 mg/kg，静脉推注）的急性血流动力学效应。大鼠分为7组：地高辛抗体片段（30 mg/kg，溶于1 mL 0.9%氯化钠中静脉推注）加假手术组（n = 6）或ACTH组（n = 8），假地高辛抗体片段（1 mL 0.9%氯化钠静脉推注）加ACTH组（n = 7），地高辛抗体片段溶媒（1.8 mg山梨醇溶于1 mL 0.9%氯化钠中，静脉推注）加假手术组（n = 6），免疫前羊IgG（30 mg/kg溶于1 mL 0.9%氯化钠中静脉推注）加假手术组（n = 6）或ACTH组（n = 6）以及免疫前羊IgG（Fab）2片段（30 mg/kg溶于1 mL 0.9%氯化钠中静脉推注）加ACTH组（n = 6）。在治疗第10天，ACTH使收缩压（SBP）从118±2 mmHg升高至132±3 mmHg。假手术治疗的大鼠血压无变化。地高辛抗体片段的急性给药使ACTH高血压大鼠的平均动脉压（MAP）降低（-14±3 mmHg，P<.001），但在ACTH假手术对照的正常血压大鼠中未降低（+2±3 mmHg）。血压在14±3分钟后降至最低，且效应持续超过30分钟。接受假（0.9%氯化钠）地高辛抗体片段注射的ACTH治疗大鼠血压无显著变化（+2±2 mmHg）。然而，免疫前羊IgG和IgG（Fab）2片段在假手术或ACTH治疗的大鼠中均导致血压降低。尽管地高辛抗体片段使ACTH治疗但非假手术治疗大鼠血压降低的数据与洋地黄样物质可能在ACTH诱导的高血压中起作用的观点一致，但免疫前羊IgG和IgG（Fab）2片段也使大鼠血压降低的证据提示在解释使用地高辛抗体片段制剂的研究时应谨慎。
