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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SpragueDawley(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(50,100 mg·kg~(-1)),每组12只。MCT(60 mg·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-time PCR和Western blot检测肺动脉collagen I,NOX2及NOX4 mRNA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,collagen I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。
Objective: To observe the effects of sesamin (Ses) on pulmonary vascular remodeling induced by monocrotaline (MCT) in rats with pulmonary hypertension (PH). Methods: Forty eight male Sprague Dawley (SD) rats were fed for 1 week. They were randomly divided into normal control group, MCT group and low and high dose Ses group (50, 100 mg · kg -1) with 12 rats in each group. MC model rats were induced by subcutaneous injection of MCT (60 mg · kg -1). Four weeks after continuous administration, right ventricular systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) were measured by right external jugular vein catheterization. The right ventricle (RV), left ventricular + ventricular septum (LV + S) were isolated and weighed, the rat tibia was dissected and its length measured. The ratio of RV / (LV + S) and RV / tibia length was calculated. The pathological changes of pulmonary arterioles were observed by HE staining and the changes of collagen deposition in pulmonary arterioles were observed by Masson staining. The expression of α-smooth muscle actin (α-SMA) in pulmonary artery was detected by immunohistochemistry. The contents of T-AOC and MDA in pulmonary arteries were measured by colorimetry. Real-time PCR and Western blot were used to detect mRNA and protein expression of collagen I, NOX2 and NOX4 in pulmonary arteries. RESULTS: After 4 weeks of continuous administration, Ses significantly reduced the RVSP and mPAP, decreased the ratios of RV / (LV + S) and RV / tibia in MCT-induced PH rats, decreased the expression of α-SMA and collagen I in the pulmonary artery, Vascular and right ventricular remodeling. At the same time, Ses also significantly inhibited pulmonary artery NOX2 and NOX4 expression, reduce its MDA content and improve T-AOC levels. CONCLUSIONS: Ses can relieve pulmonary vascular remodeling induced by MCT in PH rats, and its mechanism may be related to the inhibition of the expression of NOX2 and NOX4, thereby reducing the oxidative stress injury.