Palei Ana C, Spradley Frank T, Granger Joey P
Department of Physiology and Biophysics and Cardiovascular Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi.
Department of Physiology and Biophysics and Cardiovascular Renal Research Center, University of Mississippi Medical Center, Jackson, Mississippi
Am J Physiol Regul Integr Comp Physiol. 2015 May 15;308(10):R855-61. doi: 10.1152/ajpregu.00286.2014. Epub 2015 Mar 11.
Despite the fact that obesity is a major risk factor for preeclampsia (PE), the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increase this risk are unclear. While human data have shown that hyperleptinemia is associated with PE, the long-term effect of hyperleptinemia on blood pressure during pregnancy is unknown. Thus we tested the hypothesis whether chronic circulating leptin elevations in pregnant rats increase blood pressure and placental factors known to play a role in PE. On gestational day (GD)14, rats were assigned to the normal pregnant group with food intake ad libitum (control), leptin-treated (0.5 μg·kg(-1)·min(-1) ip) pregnant group with food intake ad libitum (pregnant+LEP), and normal pregnant group with food intake adjusted to the food intake of pregnant+LEP rats (pregnant-FR). On GD19, mean arterial pressure (MAP) was assessed and tissues were collected. Serum leptin concentration was elevated in pregnant+LEP compared with control and pregnant-FR (18.0 ± 2.8 vs. 0.8 ± 0.1 vs. 0.3 ± 0.1 ng/ml; P < 0.05), which was associated with increased MAP (121.3 ± 8.1 vs. 102.4 ± 2.4 vs. 101.3 ± 1.8 mmHg; P < 0.05). Food intake and body weight were reduced in pregnant+LEP and pregnant-FR by the end of gestation. Additionally, placentas and fetuses of these groups were lighter than those of control. However, placental expression of tumor necrosis factor-α was significantly greater in pregnant+LEP compared with controls (1.6 ± 0.1 vs. 1.1 ± 0.1 pg/mg; P < 0.05). In conclusion, leptin increases blood pressure and placental tumor necrosis factor-α during pregnancy despite its effect of reducing food intake and body weight, and represents a mechanism whereby obesity can promote the development of hypertension in PE.
尽管肥胖是先兆子痫（PE）的主要危险因素，但肥胖及瘦素等代谢因素增加该风险的病理生理机制尚不清楚。虽然人体数据显示高瘦素血症与PE有关，但高瘦素血症对孕期血压的长期影响尚不清楚。因此，我们检验了这样一个假设：妊娠大鼠慢性循环瘦素升高是否会升高血压以及增加已知在PE中起作用的胎盘因子。在妊娠第14天，将大鼠分为自由进食的正常妊娠组（对照组）、自由进食的瘦素处理组（0.5μg·kg(-1)·min(-1)腹腔注射）（妊娠+LEP组）和食物摄入量调整为妊娠+LEP组大鼠摄入量的正常妊娠组（妊娠-FR组）。在妊娠第19天，评估平均动脉压（MAP）并收集组织。与对照组和妊娠-FR组相比，妊娠+LEP组血清瘦素浓度升高（18.0±2.8 vs. 0.8±0.1 vs. 0.3±0.1 ng/ml；P<0.05），这与MAP升高有关（121.3±8.1 vs. 102.4±2.4 vs. 101.3±1.8 mmHg；P<0.05）。到妊娠末期，妊娠+LEP组和妊娠-FR组的食物摄入量和体重均降低。此外，这些组的胎盘和胎儿比对照组的更轻。然而，与对照组相比，妊娠+LEP组胎盘肿瘤坏死因子-α的表达明显更高（1.6±0.1 vs. 1.1±0.1 pg/mg；P<0.05）。总之，瘦素在孕期虽有减少食物摄入量和体重的作用，但仍会升高血压和胎盘肿瘤坏死因子-α，这代表了肥胖促进PE高血压发展的一种机制。
