摘要
目的评价西地那非对肺动脉高压大鼠肺组织己糖激酶-2（HK-2）表达的影响。方法雄性SD大鼠32只，2月龄，体重200-220 g，采用随机数字表法分为4组（n＝8）：对照组（C组）、肺动脉高压组（PAH组）、低剂量西地那非组（S1组）和高剂量西地那非组（S2组）。采用左肺切除术联合皮下注射野百合碱60 mg/kg的方法制备肺动脉高压模型。S1组和S2组肺切除术后5周时分别给予2%枸橼酸西地那非30、50 mg/kg灌胃，1次/d，连续3周。给药结束后，开胸测定平均肺动脉压（mPAP）和右心室收缩压（RVSP）。取心、肺组织，行HE染色，测定肺小动脉中膜厚度（MT）百分比和右心室心肌细胞面积，采用免疫组化法测定肺血管α-平滑肌肌动蛋白（α-SMA）表达，采用Western blot法测定肺组织缺氧诱导因子-1α（HIF-1α）以及HK-2的表达。结果与C组比较，PAH组和S1组mPAP、RVSP和MT百分比升高，右心室心肌细胞面积增大，肺组织HIF-1α、HK-2及α-SMA表达上调，S2组RVSP和MT百分比升高，右心室心肌细胞面积增大，肺组织HIF-1α、HK-2及α-SMA表达上调（P〈0.05），mPAP差异无统计学意义（P〉0.05）。与PAH组比较，S1组MT百分比降低，右心室心肌细胞面积减小，肺组织HIF-1α、HK-2及α-SMA表达下调，S2组mPAP、RVSP和MT百分比降低，右心室心肌细胞面积减小，肺组织HIF-1α、HK-2及α-SMA表达下调（P〈0.05）。结论西地那非抑制肺动脉高压大鼠肺血管平滑肌细胞增殖的机制与抑制HK-2表达有关。
Objective To evaluate the effect of sildenafil on the expression of hexokinase-2 （HK-2） in lung tissues in a rat model of pulmonary arterial hypertension.Methods Thirty-two male Sprague-Dawley rats, aged 2 months, weighing 200-220 g, were allocated into 4 groups with 8 rats in each group using a random number table： control group （group C）, pulmonary arterial hypertension group （group PAH）, low-dose sildenafil group （group S1） and high-dose sildenafil group （group S2）. The model of pulmonary arterial hypertension was established through combining left pneumonectomy with subcutaneous injection of 60 mg/kg monocrotaline.Two percent sildenafil 30 and 50 mg/kg were administered by intragastric gavage once a day for 3 consecutive weeks starting from 5 weeks after pneumonectomy in S1 and S2 groups, respectively.The chest was opened after the end of administration for measurement of mean pulmonary arterial pressure （mPAP） and right ventricular systolic pressure （RVSP）. The hearts and lungs were excised for determination of the percentage of the thickness of tunica media of pulmonary arterioles, size of right ventricular cardiomyocytes, α-smooth muscle actin （α-SMA） expression （by immunohistochemistry） and expression of hypoxia-inducible factor-1α （HIF-1α） and HK-2 （by Western blot）.Results Compared with group C, the mPAP, RVSP and percentage of MT were significantly increased, the size of right ventricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regulated in PAH and S1 groups, and the RVSP and percentage of MT were significantly increased, the size of right ventricular cardiomyocytes was enlarged, and the expression of HIF-1α, HK-2 and α-SMA was up-regulated （P〈0.05）, and no significant change was found in mPAP in group S2 （P〉0.05）. Compared with group PAH, the percentage of MT was significantly decreased, the size of right ventricular cardiomyocytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S1, and the mPAP, RVSP and percentage of MT were significantly decreased, the size of right ventricular cardiomyocytes was decreased, and the expression of HIF-1α, HK-2 and α-SMA was down-regulated in group S2 （P〈0.05）.Conclusion The mechanism by which sildenafil inhibits proliferation of pulmonary vascular smooth muscle cells is related to inhibiting the expression of HK-2 in lung tissues in a rat model of pulmonary arterial hypertension.
作者
祝玉玲
孙青
俞春芳
杨军
李冰冰
Zhu Yuling;Sun Qing;Yu Chunfang;Yang Jun;Li Bingbing(Department of Anesthesiology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 210008, China;Department of Pathology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing 21008, China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2018年第3期371-375,共5页
Chinese Journal of Anesthesiology
基金
十三五南京市卫生青年人才培养工程（QRX17013）
江苏省六大人才高峰（2016-WSN-147）
国家自然科学基金（81470242）
关键词
磷酸二酯酶抑制剂
高血压
肺性
己糖激酶
Phosphodiesteraseinhibitors
Hypertension
pulmonary
Hexokinase
