褐藻胶寡糖对野百合碱诱导的大鼠肺动脉高压模型P选择素表达的影响  

Effect of acidic oligosaccharides on P-selectin of pulmonary hypertensive rats induced by monocrotaline

作　　者：冯喆 胡怡[1] 安妮娜[1] 冯文静[1] 胡婷[2] 毛拥军[1] 

机构地区：[1]青岛大学附属医院,青岛266003 [2]中国海洋大学

出　　处：《中华结核和呼吸杂志》2018年第2期90-94,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：青岛市民生科技计划项目(15-9-2-75-nsh)

摘　　要：目的观察褐藻胶寡糖（AOS）对野百合碱诱导的大鼠肺动脉高压模型P选择素表达的影响。方法60只雄性SD大鼠根据随机数字表法分为对照组、模型组、前列地尔组、褐藻胶寡糖低剂量（AOS－L）组、褐藻胶寡糖中剂量（AOS－M）组及褐藻胶寡糖高剂量（AOS－H）组，每组10只，采用一次性腹腔注射野百合碱（60 mg/kg）的方法建立肺动脉高压模型。造模成功后，前列地尔组腹腔注射前列地尔5 μg·kg^-1·d^-1，AOS－L组、AOS－M组及AOS－H组分别腹腔注射褐藻胶寡糖5、10及20 mg·kg^-1·d^-1。对照组与模型组每天腹腔注射0.9%氯化钠溶液3 ml/kg。记录大鼠的死亡情况。给药3周后，测定大鼠的肺动脉血流加速时间（PAT）、肺动脉射血时间（ET）及肺动脉内径值。分离大鼠心脏，计算大鼠的右心室肥厚指数（RVHI）并观察肺组织病理。采用酶联免疫吸附试验和Western blot法分别测定血浆和肺动脉P选择素的表达情况。结果与对照组比较，模型组病死率较高。模型组RVHI（0.677±0.047）高于对照组，PAT/ET（0.179±0.008）低于对照组（均P〈0.01）。AOS－L组、AOS－M组及AOS－H组大鼠生存情况较模型组明显改善，RVHI明显低于模型组，分别为0.539±0.049、0.502±0.034、0.446±0.045（均P〈0.01），PAT/ET明显高于模型组，分别为0.170±0.023、0.231±0.053、0.351±0.369（均P〈0.05）。组织病理学可见模型组肺中小动脉内皮细胞连续性破坏，管壁厚度增加，管腔面积缩小，伴有明显的血管周围炎，管腔内可见原位血栓形成，肺泡内可见心力衰竭细胞。AOS组血栓形成减少，血管周围炎症减轻。与对照组比较，模型组血浆和肺动脉中P选择素的表达明显增高（P〈0.01），AOS组P选择素的表达降低（P〈0.01）。结论AOS降低野百合碱诱导的大鼠肺动脉高压模型P选择素的表达，该作用呈浓度依赖性。Objective To observe the effects of acidic oligosaccharides （AOS） on P-selectin levels in the serum and the pulmonary arteries of pulmonary hypertensive rats induced by monocrotaline. Methods Sixty healthy adult male Sprague-Dawley rats were randomly divided into control group （ n = 10 ）, model group （n = 10）, Alprostadil group （n = 10）, low-dose AOS group （AOS-L, n= 10）, medium-dose AOS group （AOS-M, n = 10） and high-dose AOS group （AOS-H, n = 10）. The rat model of pulmonary arterial hypertension was made by a single intraperitoneal injection of monocrotaline（ 60 mg/kg）. Five weeks after injection, pulmonary arterial （PA） acceleration time （PAT） and ejection time （ET） were measured by color Doppler ultrasound. Then, the Alprostadil group was treated by Alprostadil 5 μg·kg^-1·d^-1 intraperitoneally. Acidic oligosaccharides was administered by intraperitoneal injection to rats in the AOS-L group（5 kg^-1·d^-1）, AOS-M group （10 mg·kg^-1·d^-1） and AOS-H group （20 mg·kg^-1·d^-1）. Control group and model group were given normal saline instead. At the end of experiments, the death rate was recorded and PAT/ET was measured. We calculated the right ventrieular hypertrophy index （RVHI） of all rats sacrificed under anesthesia. Precision-cut lung slices were stained with HE for observation of the structure of middle and small arteries. The expression level of P-selectin in serum and pulmonary arterial tissues were detected by ELISA and Western blot respectively. Results AOS significantly increased the level of PAT/ET （P 〈0. 01 ）, and attenuated RVHI （P 〈0. 01）. AOS significantly improved intima-media proliferation in small-to medium-sized pulmonary arteries, and attenuated perivascular inflammation. AOS and Alprostadil significantly down-regulated the protein expression of P-selectin in serum and pulmonary arteries （P 〈 0.01 ）. Conclusion In this rat model of monocrotaline-induced pulmonary hypertension, AOS decreased the expressions of P-s

关 键 词：褐藻胶寡糖 肺动脉高压 P选择素 野百合碱 

分 类 号：R544.1[医药卫生—心血管疾病]