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芝麻素对野百合碱诱导的肺动脉高压大鼠肺血管重构的影响

Keywords: 芝麻素,肺动脉高压,NOX2,NOX4,氧化应激

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Abstract:

目的:观察芝麻素(Ses)对野百合碱(MCT)诱导的肺动脉高压(PH)大鼠肺血管重构的影响。方法:雄性Sprague-Dawley(SD)大鼠48只适应性喂养1周,随机分为正常对照组、MCT组、Ses低、高剂量组(50,100mg·kg-1),每组12只。MCT(60mg·kg-1)皮下注射诱导PH大鼠模型。连续给药4周后,右颈外静脉插管测定大鼠右心室收缩压(RVSP)、平均肺动脉压(mPAP)。分离大鼠右心室(RV)、左心室+室间隔(LV+S)并称重,剥离大鼠胫骨并测量其长度,计算RV/(LV+S)及RV/胫骨长度的比值。HE染色观察肺小动脉病理学变化,Masson染色观察肺小动脉胶原沉积的变化。免疫组化检测肺动脉α-平滑肌肌动蛋白(α-SMA)的表达。比色法测定肺动脉总抗氧化能力(T-AOC)及丙二醛(MDA)含量。Real-timePCR和Westernblot检测肺动脉collagenI,NOX2及NOX4mRNA和蛋白表达。结果:Ses连续给药4周后能明显降低MCT诱导的PH大鼠RVSP及mPAP,减轻RV/(LV+S)及RV/胫骨长度的比值,降低肺动脉α-SMA,collagenI表达、减轻肺血管及右心室重构。同时,Ses还能明显抑制肺动脉NOX2及NOX4的表达,降低其MDA含量及提高T-AOC水平。结论:Ses能够缓解MCT诱导的PH大鼠肺血管重构,其机制可能与抑制NOX2及NOX4的表达、进而降低氧化应激损伤有关。

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