过氧化物酶体增殖物活化受体-β/δ激动剂GW501516对老龄脓毒症大鼠心功能的影响

Effect of peroxisome proliferators-activated receptor-β/δ agonist GW501516 on cardiac function in aged septic rats

摘要:

目的 研究过氧化物酶体增殖物激活受体（PPAR）-β/δ激动剂GW501516对老龄脓毒症大鼠心功能的影响。方法 用盲肠结扎穿孔术（CLP）制备老龄大鼠脓毒症模型。50只老龄雄性SD大鼠，随机分为4组，分别为空白对照组（Con，n＝5）、假手术组（Sham组，n＝6）、CLP组，（n＝19）、CLP手术后应用GW501516液（0.05mg/100g）干预组（CLP＋GW组，n＝20）。记录术后48h内各组大鼠死亡情况，在术后48h利用超声心动图评价各组大鼠心率、每搏输出量、心指数、左室舒张末期内径、左室舒张末期容积等心功能指标。结果 与单纯CLP组相比，CLP＋GW组组的老龄大鼠48h内死亡率降低（42.1% vs 15.0%，P＜0.05）。术后48h超声心动图显示，CLP＋GW组老龄大鼠与CLP组比较，心率明显降低[（318.55±16.65）vs（411.16±10.1）次/min，P＜0.01]；每搏输出量[（470.71±111.6） vs （171.47±39.85）ml/搏，P＜0.05]、心指数[（185.00±41.2） vs （102.05±19.94）ml/（min·mm2），P＜0.05]均较单纯CLP手术组显著升高；反映舒张功能的指标，左室舒张末期内径[（8.02±0.66） vs （5.65±0.45）mm，P＜0.05]和左室舒张末期容积[（5.13±1.00） vs （1.75±0.39）ml，P＜0.01]也较CLP组有明显增加。结论 在早期给予老龄脓毒症大鼠GW501516进行液体复苏，可降低早期死亡率，明显改善心脏收缩与舒张功能，改善心脏做功。

Abstract:

Objective To determine the influence of peroxisome proliferator-activated receptor (PPAR)-β/δ agonist, GW501516 (GW), on the cardiac function in aged septic rats. Methods The aged rat model of sepsis was established by cecal ligation and puncture surgery (CLP). Totally 50 aged rats (24 months old) were randomly divided into 4 groups: control group (Con, n＝5), sham operation group (Sham, n＝6), CLP group (n＝19), CLP+GW501516 (0.05mg/100g) group (n＝20). The mortality of the aged rats was recorded within 48 h after the CLP surgery. In 48h after CLP, the heart rate, stroke volume (SV), cardiac index (CI), left ventricular end-diastolic diameter and left ventricular end-diastolic volume were evaluated by echocardiography. Results CLP+GW group had significantly reduced mortality compared with CLP group (15.0% vs 42.1%, P＜0.05). The echocardiographic results showed that GW501516 resulted in greatly declined heart rate [(318.55±16.65) vs (411.16±10.1) beats/min, P＜0.01], and extremely increased SV and CI in 48h after surgery [(470.71±111.6) vs (171.47±39.85)ml/beat, P＜0.05; (185.00±41.2) vs (102.05±19.94)ml/(min·mm-2), P＜0.05] when compared with simple CLP operation. Left ventricular end-diastolic diameter and left ventricular end-diastolic volume were also significantly improved in CLP+GW501516 group compared with CLP group[(8.02±0.66) vs (5.65±0.45)mm, P＜0.05; (5.13±1.00) vs (1.75±0.39)ml, P＜0.01]. Conclusion Early application of PPARβ/δ agonist GW501516 reduces the mortality and improves cardiac systolic and diastolic function in aged septic rats.