Prenatal cocaine exposure increases heart susceptibility to ischaemia-reperfusion injury in adult male but not female rats
Prenatal cocaine exposure increases heart susceptibility to ischaemia-reperfusion injury in adult male but not female rats
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DOI：
10.1113/jphysiol.2005.082701
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发表时间：
2005-05-15
影响因子：
5.5
通讯作者：
Zhang, LB
中科院分区：
文献类型：
--
作者：
Bae, S;Gilbert, RD;Zhang, LB
本研究检验了以下假设：产前可卡因暴露会差异调节成年雄性和雌性后代后代缺血再灌注 (I/R) 损伤的心脏易感性。从孕龄第15天到第21天，怀孕大鼠腹腔内注射生理盐水或可卡因（15 mg kg(-1)），每天两次。两组之间的母亲体重增加和出生体重没有差异。从 2 个月大的雄性和雌性后代中分离心脏，并在 Langendorff 制剂中进行 I/R（25 分钟/60 分钟）。对于雄性和雌性大鼠，生理盐水对照心脏和可卡因治疗心脏之间的左心室（LV）功能的缺血前值相同。产前接触可卡因显着增加缺血再灌注诱导的心肌细胞凋亡和梗塞面积，并显着减弱成年男性后代左心室功能的缺血后恢复。相比之下，可卡因并不影响缺血再灌注引起的女性心脏损伤和左心室功能的缺血后恢复。在出生前接触可卡因的雄性后代中，左心室中的 PKC epsilon 和磷酸化 PKC epsilon 水平显着下降，而雌性后代则没有。这些结果表明，产前接触可卡因会导致成年男性后代心脏对 I/R 损伤的敏感性增加，而男性心脏中 PKC epsilon 基因表达的降低可能发挥重要作用。
The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia-reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg(-1)) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKC epsilon and phospho-PKC epsilon levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKC epsilon gene expression in the male heart may play an important role.