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观察白杨素(chrysin,5,7-二羟基黄酮)对野百合碱(monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠右心室重构的影响及其机制。Sprague-Dawley大鼠适应性喂养1周,随机分为正常对照组、MCT组、MCT+chrysin(50 mg·kg-1·d-1)及MCT+chrysin(100 mg·kg-1·d-1)剂量组。MCT(60 mg·kg-1)皮下注射诱导PAH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(m PAP)。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染色观察右心室病理学变化,Masson染色观察右心室胶原沉积的变化。比色法测定右心室总抗氧化能力(T-AOC)和丙二醛(MDA)含量。q PCR、Western blot和(或)免疫组化检测右心室collagen I、collagen III、NADPH氧化酶4(NADPH oxidase 4,NOX4)、核转录因子κB(nuclear factor-kappa B,NF-κB)m RNA和蛋白表达。结果发现,白杨素连续给药4周后能明显降低MCT诱导的PAH大鼠RVSP及m PAP,减轻RV/(LV+S)及RV/胫骨长度的比值,改善右心室病理变化,降低右心室胶原的沉积及collagen I、collagen III的表达,提高右心室T-AOC水平,降低NOX4的表达及MDA含量,抑制NF-κB的表达。结果表明,白杨素能缓解MCT诱导的PAH大鼠右心室重构,其机制可能与其抑制NOX4介导的氧化应激损伤,进而抑制NF-κB所介导的胶原沉积有关。
To observe the effect and mechanism of chrysin (5,7-dihydroxyflavone) on right ventricular remodeling induced by monocrotaline (MCT) in rats with pulmonary arterial hypertension (PAH). Sprague-Dawley rats were fed for 1 week and were randomly divided into normal control group, MCT group, MCT + chrysin (50 mg · kg -1 · d -1) and MCT + chrysin (100 mg · kg -1 · d- 1) dose group. PAH rat model was 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. Right ventricular pathological changes were observed by HE staining and Masson staining was used to observe the changes of collagen deposition in the right ventricle. The contents of T-AOC and MDA in the right ventricle were measured by colorimetry. qPCR, Western blot and / or immunohistochemistry were used to detect the expression of collagen I, collagen III, NADPH oxidase 4 (NOX4), nuclear factor-kappa B (NF-κB) And protein expression. The results showed that chrysin significantly reduced the RVSP and m PAP, the ratio of RV / (LV + S) and RV / tibia in MCT-induced PAH rats, and improved the right ventricular pathological changes and the right ventricular Collagen deposition and collagen I, collagen III expression, improve right ventricular T-AOC levels, reduce the expression of NOX4 and MDA content, inhibit the expression of NF-κB. The results showed that chrysin can relieve the right ventricular remodeling induced by MCT in PAH rats, which may be related to the inhibition of NOX4-mediated oxidative stress injury and the inhibition of NF-κB-mediated collagen deposition.