围产期高盐饮食对雄性子代大鼠肠系膜动脉DDAH2/ADMA/eNOS/NO通路的影响

The Effect of Maternal Perinatal High-salt Diet on DDAH2/ADMA/eNOS/NO Pathway of Mesenteric Artery in Male Offspring Rats

目的探讨围产期高盐饮食对雄性子代大鼠肠系膜动脉二甲基精氨酸二甲胺水解酶2(DDAH2)/非对称性二甲基精氨酸(ADMA)/内皮型一氧化氮合酶(e NOS)/一氧化氮(NO)通路的影响。方法实验大鼠分为2组:正常饮食(NSD)组和高盐饮食(HSD)组,分别在围产期以普通饲料(含1%Na Cl)和高盐饲料(含8%Na Cl)喂养,分娩后雄性子鼠继续相同饲料喂养至16周。测量子鼠血压,检测肠系膜动脉内皮依赖性舒张功能,检测血浆和肠系膜动脉NO含量、e NOS活性、ADMA含量,检测肠系膜动脉DDAH2活性及DDAH1和DDAH2蛋白质表达水平。结果 16周时,HSD组收缩压显著高于NSD组(P<0.01)。HSD组大鼠肠系膜血管张力低于NSD组(P<0.01);用ADMA孵育血管环后,NSD组血管张力显著减弱,而HSD组未见显著性变化。与NSD组比较,HSD组血浆NO含量降低(P<0.05),e NOS活性降低(P<0.01),ADMA含量增加(P<0.05);HSD组肠系膜动脉NO含量下降(P<0.01),e NOS活性下降(P<0.01),ADMA含量升高(P<0.05)。HSD组DDAH2活性降低(P<0.01),DDAH2蛋白质表达显著降低(P<0.01);DDAH1蛋白质表达未见显著改变。HSD组肠系膜动脉指标相关性分析:e NOS活性与NO含量呈正相关,ADMA含量与e NOS活性呈负相关,DDAH2活性、DDAH2蛋白质表达与ADMA含量呈负相关。结论母体围产期高盐饮食导致其雄性子代收缩压增高,肠系膜动脉内皮依赖性舒张功能障碍,此与肠系膜动脉DDAH2表达下降、活性降低和DDAH2/ADMA/e NOS/NO通路障碍有关。

Aim To investigate the effect of maternal perinatal high-salt diet on dimethylarginine dimethylaminohydrolase 2（ DDAH2） / asymmetric dimethylarginine（ ADMA） / endothelial nitric oxide synthase（ e NOS） / nitric oxide（ NO） pathway of the mesenteric artery in the male offspring rats. Methods The rats were divided into 2 groups： normal-salt diet（ NSD） group and high-salt diet（ HSD） group,and fed respectively with normal-salt diet（ 1% Na Cl） and high-salt diet（ 8%Na Cl） during perinatal period. After delivery,the male offspring rats were fed with the same diet for 16 weeks. Blood pressure,mesenteric artery endothelial-dependent diastolic function,NO content,e NOS activity and ADMA content in plasma and mesenteric artery,DDAH2 activity and protein expression of DDAH1 and DDAH2 in mesenteric artery were detected by various methods. Results The systolic blood pressure（ SBP） in HSD group was significantly higher than that in NSD group（ P 0. 01）. The endothelium-dependent tension of mesenteric artery in HSD group was lower than that in NSD group（ P 0. 01）. After incubation with ADMA,the blood vessel tension was significantly decreased in NSD group,while no significant change was found in HSD group. Compared with the NSD group,NO content was decreased（ P〈 0. 05）,e NOS activity was decreased（ P 0. 01）,ADMA content was increased（ P 0. 05） in plasma in HSD group,and NO content was decreased（ P 0. 01）,e NOS activity was decreased（ P 0. 01）,ADMA content was increased（ P〈 0. 05） on mesenteric artery in HSD group. In HSD group,DDAH2 activity and protein expression were decreased（ P〈 0. 01）,but DDAH1 protein expression was not changed significantly. In HSD group,correlation analysis of mesenteric arterial indexes showed that e NOS activity was positively correlated with NO content,ADMA content was negatively correlated with e NOS activity,DDAH2 activity and DDAH2 protein expression were negatively correlated with ADMA content. Conclusion The high-salt diet in the maternal perinatal period results in the increase of SBP and the endothelial-dependent diastolic dysfunction on mesenteric arteries in male offspring rats,which are related to the decrease of DDAH2 activity and the disorder of DDAH2 / ADMA / e NOS / NO pathway in mesenteric arteries.