Strande Jennifer L, Routhu Kasi V, Lecht Shimon, Lazarovici Philip
Division of Cardiovascular Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
J Basic Clin Physiol Pharmacol. 2013;24(1):81-4. doi: 10.1515/jbcpp-2012-0045.
Nerve growth factor (NGF) is a neurotrophin that supports the survival and differentiation of sympathetic neurons, and its increased expression after myocardial infarct was correlated with cardiac sympathetic hyperinnervation and arrhythmias. However, it is unclear whether NGF protects the heart during infarct. In this study, we sought to address this issue in rat heart exposed to ischemia/reperfusion injury (IRI).
NGF was administered intravenously (IV), 15 min before ischemia, at different concentrations in the absence or presence of inhibitors of phosphatidylinositol-3 kinase (PI3K) or nitric oxide synthase (NOS) in different groups of rats (n=6) with left coronary occlusion for 30 min followed by 120-min reperfusion. The area at risk and infarct to risk ratios were determined from sections stained with 1% 2,3,5-triphenylterazolium chloride.
NGF treatment at doses of 0.015-15 μg/kg, with an optimal dose of 0.15 μg/kg given IV before ischemia, reduced the infarct size from about 60% at the area of risk to about 25%, indicating cardioprotection by about 60%. The infarct-sparing effects of NGF were partially abolished by the inhibition of PI3K and NOS using wortmannin and N(G)-monomethyl-l-arginine, respectively.
We have demonstrated for the first time that NGF attenuates myocardial infarct damage in an in vivo rat model of myocardial regional IRI. This cardioprotective effect is proposed to be related to the activities of PI3K and NOS. This suggests that NGF has a potential therapeutic role in the treatment of IRI.
神经生长因子（NGF）是一种神经营养因子，可支持交感神经元的存活和分化，心肌梗死后其表达增加与心脏交感神经超支配及心律失常相关。然而，尚不清楚NGF在梗死期间是否对心脏具有保护作用。在本研究中，我们试图在暴露于缺血/再灌注损伤（IRI）的大鼠心脏中解决这一问题。
在不同组（n = 6）的大鼠中，于缺血前15分钟静脉内（IV）给予不同浓度的NGF，在不存在或存在磷脂酰肌醇-3激酶（PI3K）或一氧化氮合酶（NOS）抑制剂的情况下，左冠状动脉闭塞30分钟，随后再灌注120分钟。通过用1% 2,3,5-三苯基氯化四氮唑染色的切片确定危险区域和梗死与危险区域的比值。
在缺血前静脉给予剂量为0.015 - 15μg/kg的NGF，最佳剂量为0.15μg/kg，可将梗死面积从危险区域的约60%减少至约25%，表明心脏保护作用约为60%。分别使用渥曼青霉素和N(G)-单甲基-L-精氨酸抑制PI3K和NOS可部分消除NGF的梗死面积缩小作用。
我们首次证明，在心肌局部IRI的体内大鼠模型中，NGF可减轻心肌梗死损伤。这种心脏保护作用被认为与PI3K和NOS的活性有关。这表明NGF在IRI治疗中具有潜在的治疗作用。
