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Title: [Effect of acidic oligosaccharides on P-selectin of pulmonary hypertensive rats induced by monocrotaline].
Author: Feng Z, Hu Y, An NN, Feng WJ, Hu T, Mao YJ.
Journal: Zhonghua Jie He He Hu Xi Za Zhi; 2018 Feb 12; 41(2):90-94. PubMed ID: 29429213.
Abstract:
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 ventricular 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-selectin in serum and pulmonary arteries in a dose-dependent manner. 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。.

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