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对一种贝特类药物(PPARα的特异性激动剂)作为治疗临床绵羊妊娠毒血症替代疗法的评估。

Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia.

作者信息

Da Silva S, Cal-Pereyra L G, Benech A, Acosta-Dibarrat J, Martin M J, Abreu M C, Perini S, González-Montaña J R

机构信息

Pathology Department, Veterinary Faculty, University of La República, Montevideo, Uruguay.

Small Animals Department, Veterinary Faculty, University of La República, Montevideo, Uruguay.

出版信息

J Vet Pharmacol Ther. 2016 Oct;39(5):497-503. doi: 10.1111/jvp.12304. Epub 2016 Mar 11.

Abstract

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator-activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty-three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2-methyl-2-phenoxy-propionic acid; 10 mg/kg of 2-methyl-2-phenoxy-propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum β-hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2-methyl-2-phenoxy-propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2-methyl-2-phenoxy-propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.

摘要

绵羊妊娠毒血症是一种代谢紊乱疾病,影响怀孕最后6周的绵羊,原因是它们无法维持足够的能量稳态。有多种不同的替代治疗方法,效果各异。本研究的目的是评估一种过氧化物酶体增殖物激活受体α(PPARα)激动剂作为治疗临床妊娠毒血症的替代方法。33只成年绵羊,已知妊娠日期且怀有单胎,从妊娠第130天开始禁食,直至动物出现临床疾病。从那时起,绵羊在6天内接受三种不同的治疗方案:10mg/kg的2-甲基-2-苯氧基丙酸;10mg/kg的2-甲基-2-苯氧基丙酸 + 100mL口服丙二醇;或100mL口服丙二醇。每天测定血糖和血清β-羟基丁酸(BHOB)。在妊娠第130天、治疗开始和结束时以及产后5天进行肝脏活检,评估脂肪变性病变的程度和范围。尽管用2-甲基-2-苯氧基丙酸治疗的绵羊中,葡萄糖和BHOB的血清浓度恢复较慢,但我们得出结论,单独使用2-甲基-2-苯氧基丙酸或与丙二醇联合使用可作为有效治疗脂肪肝及妊娠毒血症的替代方法。

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