摘要
目的探讨高游离脂肪酸(FFA)血症是否可诱发高血压及可能机制。方法 12周龄雄性SD大鼠随机分为3组:对照组(n=20),FFA组(n=22)及N乙酰半胱氨酸组(NAC组,n=23)。大鼠行颈静脉插管输注液体,对照组大鼠采用生理盐水(18μL/min)输注,FFA组大鼠采用20%脂肪乳(18μL/min)+肝素(0.72U/min)输注,NAC组大鼠给予20%脂肪乳(18μL/min)+肝素(0.72U/min)+NAC[2.76μmol/(kg.min)]输注,时间均为4h。记录输注过程中大鼠血压变化;采用正常血糖高胰岛素钳夹试验评价胰岛素抵抗程度;观察离体主动脉环对乙酰胆碱或硝普钠的舒张反应;测定血中FFA、活性氧、还原型谷胱甘肽(GSH)及NO2-/NO3-水平;实时荧光定量PCR方法检测大鼠主动脉内皮型一氧化氮合酶(eNOS)mRNA表达水平。结果 FFA组大鼠收缩压和舒张压分别较基础状态升高了(11.5±2.2)和(6.0±1.2)mmHg(均P<0.05)。NAC组血压较前无明显变化。FFA组葡萄糖输注率(GIR)明显低于对照组[(5.3±0.6)比(13.4±0.5)mg/(kg.min),P<0.05]。FFA组主动脉环对乙酰胆碱的舒张反应明显受损(P<0.05),对硝普钠的反应与对照组无明显差别(P>0.05)。FFA组活性氧水平明显高于对照组,GSH水平明显低于对照组(均P<0.05)。FFA组与对照组相比,血NO2-/NO3-水平明显降低,eNOSmRNA表达降低41.2%(均P<0.05),NAC组与FFA组相比,血NO2-/NO3-水平明显升高,eNOSmRNA表达上升30.5%(均P<0.05)。结论高FFA血症可引起血压升高,可能是通过抑制内皮细胞eNOSmRNA表达从而导致内皮依赖性血管舒张功能受损,氧化应激在其中也起了重要作用。
Objective To investigate the possible mechanism of oxidative stress in the high free fatty acids（FFA）-induced hypertension.Methods Male Sprague-Dawley（SD）rat models were established and classified into three groups：control group（NC group,n=20）,FFA group（n=22）,and N-acetylcysteine group（NAC group,n=23）.NC group received a 4h infusion of saline（18 μL/min）,FFA group received a 4h infusion of 20% fat emulsion（intralipid,18 μL/min）＋ heparin（0.72 U/min）,and NAC group received a 4h infusion of intralipid（18 μL/min）＋ heparin（0.72 U/min）and NAC [2.76 μmol/（kg·min）].Blood pressure was recorded using intraarterial recording method.The hyperinsulinemic-euglycemic clamp technique was performed to investigate insulin resistance.An organ chamber experiment was performed to determine endothelium-dependent vasodilation（EDV）or endothelium-independent vasodilation（EIV）.FFAs,reactive oxygen species（ROS）,glutataione（GSH）and NO2-/NO3-levels in plasma were measured.Endothelial nitric oxide synthase（eNOS）mRNA expression in endothelial cells was evaluated by real time fluorescence-PCR.Results In FFA group,after 4 h infusion of the intralipid＋heparin,systolic and diastolic blood pressure were increased by（11.5±2.2）and（6.0±1.2）mm Hg respectively（P0.05）.In NAC group,systolic and diastolic blood pressure remained the same.The GIR was decreased significantly in FFA group compared with NC group [（5.3±0.6）vs（13.4±0.5）mg/（kg·min）,P0.05].In FFA group,the aortic rings tended to demonstrate impaired EDV in response to acetylcholine（ACh）（P0.05）.There was no difference of EDV response in NAC and NC group.ROS concentrations in FFA group were higher than that in NC group（P0.05）and GSH concentrations were lower than that in NC group（P0.05）.In FFA group,NO2-/NO3-levels were significantly reduced（P0.05）and eNOS mRNA expression was significantly decreased by 41.2% compared with NC group.NAC administration increased NO2-/NO3-levels（P0.05）and eNOS mRNA expression was significantly increased by 30.5% compared with FFA group.Conclusion Elevated FFAs can induce blood pressure elevated,potentially through FFA-induced impairment of EDV resulting from decreased eNOS mRNA expression.Oxidative stress may also play an important role in the mechanisms of this high FFA-induced elevated BP.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2011年第3期240-245,共6页
Chinese Journal of Hypertension
关键词
游离脂肪酸
高血压
氧化应激
内皮依赖性血管舒张
内皮型一氧化氮合酶
Free fatty acids
Blood pressure
Oxidative stress
Endothelium-dependent vasodilation
Endothelial nitric oxide synthase
