UNASSIGNED: Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted.
UNASSIGNED: R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues.
UNASSIGNED: R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.
■Sprague-Dawley(SD)大鼠随机分为5组,用血栓注射建立APE模型。对照组和APE组大鼠皮下注射等量的二甲基亚砜(DMSO)。APE+R-水蛭素低剂量,中等剂量,高剂量组以0.25mg/kg的剂量皮下注射水蛭素,0.5mg/kg,和1.0毫克/千克,分别。每组分为2小时的时间点,6h,1d,4d,每个点五个动物。随后,所有的老鼠都被安乐死,收集血清和肺组织。在评估右心室压(RVP)和平均肺动脉压(mPAP)后,血气分析,酶联免疫吸附测定(ELISA),肺动脉血管检查,苏木精-伊红(HE)染色,末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(TUNEL)染色,免疫组织化学,进行Western印迹实验。
■R-水蛭素治疗导致mPAP显著降低,RVP,丙二醛(MDA)含量,以及H2O2和髓过氧化物酶(MPO)活性,同时增加氧分压(PaO2)和超氧化物歧化酶(SOD)活性。R-水蛭素还降低了APE大鼠肺动脉的壁面积比和壁厚与直径比。血清内皮素-1(ET-1)和血栓素B2(TXB2)水平降低,而前列腺素(6-K-PGF1α)和NO水平升高。此外,R-水蛭素改善组织病理学损伤,减少凋亡细胞和基质金属蛋白酶-9(MMP9),血管细胞粘附分子-1(VCAM-1),肺组织中p-细胞外信号调节激酶(ERK)1/2/ERK1/2和p-P65/P65的表达。
■R-水蛭素减轻APE大鼠肺动脉高压和血栓形成,提示其作为APE新治疗策略的潜力。