Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.
Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.
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DOI：
10.1161/hypertensionaha.110.168781
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Eghbali M
中科院分区：
文献类型：
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作者：
Umar S;Nadadur RD;Li J;Maltese F;Partownavid P;van der Laarse A;Eghbali M
肺动脉高压（PAH）的特征是肺血管重构导致右心室（RV）肥大和衰竭。Intralipid®是患者的肠外营养来源，含有γ-亚麻酸和大豆来源的植物雌激素，对肺和心脏有保护作用。因此，我们研究了Intralipid®在预防和挽救单罗塔林诱导的PAH和RV功能障碍方面的治疗潜力。用60mg/kg的碱诱导雄性大鼠多环芳烃。然后大鼠从第1天到第30天每天接受Intralipid®（1mL 20% Intralipid®/天，腹腔注射）作为预防方案，从第21天到第30天用于拯救方案。其他注射了单罗塔林的大鼠在第21天发生严重的PAH，或在第30天发生RV衰竭（RVF）。生理盐水或脂内注射的大鼠作为对照组。裂谷热组rv压升高，rv射血分数降低，死亡率高。使用Intralipid®治疗可获得100%的存活率，并通过保持rv压力和rv射血分数，防止rv肥大和肺重塑来预防pah诱导的RVF。在先前存在的严重PAH患者中，Intralipid®可减轻大多数肺和RV异常。脂内酯®对PAH的有益作用似乎是多种因素相互作用的结果，其中保存和/或刺激血管生成，抑制和/或逆转肺和右心室的炎症、纤维化和肥厚似乎是主要因素。总之，Intralipid®不仅可以预防PAH和RV衰竭的发展，还可以挽救已经存在的严重PAH。
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid®, a source of parenteral nutrition for patients, contains γ-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We therefore investigated the therapeutic potential of Intralipid® in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (60mg/kg). Rats then received daily Intralipid® (1mL of 20% Intralipid®/day, intraperitoneal) from day 1 to day 30 for prevention protocol or from day 21 to day 30 for rescue protocol. Other monocrotaline-injected rats were left untreated to develop severe PAH by day 21 or RV failure (RVF) by ~day 30. Saline or Intralipid®-treated rats served as controls. Significant increase in RV-pressure and decrease in RV-ejection fraction in RVF group resulted in high mortality. Therapy with Intralipid® resulted in 100% survival and prevented PAH-induced RVF by preserving RV-pressure and RV-ejection fraction, and preventing RV-hypertrophy and lung remodeling. In pre-existing severe PAH, Intralipid® attenuated most lung and RV abnormalities. The beneficial effects of Intralipid® in PAH seem to result from interplay of various factors among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy in both lung and RV appear to be major contributors. In conclusion, Intralipid® not only prevents the development of PAH and RV failure, but also rescues pre-existing severe PAH.