藻蓝蛋白对野百合碱诱导肺动脉高压大鼠肺血管重构的影响  

Effect of phycocyanin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary arterial hypertension

作　　者：赵水炎 高帅 曹越 唐雅琪 泮思林[1] Zhao Shuiyan;Gao Shuai;Cao Yue;Tang Yaqi;Pan Silin(Heart Center,Qingdao Women and Children’s Hospital,Qingdao University,Qingdao 266034,China)

机构地区：[1]青岛大学附属妇女儿童医院心脏中心,青岛266034

出　　处：《中华实验外科杂志》2024年第2期268-271,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(82271725、81970249);山东省泰山学者工程资助(2018);青岛市科技惠民示范引导专项(23-2-8-smjk-10-nsh)。

摘　　要：目的探讨藻蓝蛋白改善肺动脉高压(PAH)大鼠肺血管重构的机制。方法将30只雄性Sprague-Dawley(SD)大鼠, 采用随机数表法分为3组:正常对照组(对照组)、PAH模型组(PAH组)、藻蓝蛋白治疗组(治疗组), 每组10只。腹腔注射野百合碱(MCT)建立PAH模型, 治疗组在造模后第15天给予藻蓝蛋白灌胃, 持续14d。测量右心室收缩压(RVSP), 计算右心室肥厚指数(RVHI)。苏木精-伊红(HE)染色、马松(Masson)染色观察肺血管, 蛋白印迹法(Western blot)检测转化生长因子-β1(TGF-β1)、核转录因子-κB(NF-κB)、B淋巴细胞瘤-2(bcl-2)、bcl-2相关X蛋白(bax)、天冬氨酸特异半胱氨酸蛋白酶-3(Caspase-3)、α-肌动蛋白(α-SMA)、增殖细胞核抗原(PCNA)表达, 免疫荧光定位α-SMA和PCNA。多组比较采用单因素方差分析。结果治疗组RVSP、RVHI低于PAH组[(24.60±3.33) mmHg比(40.49±3.76) mmHg, F=140.998, P<0.01;(32.23±2.99)%比(43.45±3.10)%, F=90.774, P<0.01], 肺小动脉中膜厚度及中膜面积百分比低于PAH组(0.579±0.013比0.736±0.023, F=251.494, P<0.01;0.574±0.063比0.917±0.036, F=84.346, P<0.05), 肺血管胶原沉积低于PAH组[(9.81±0.66)%比(23.23±2.05)%, F=294.181, P<0.01]。治疗组TGF-β1、bcl-2、α-SMA和PCNA相对表达量、磷酸化NF-κB(p-NF-κB)/NF-κB低于PAH组(0.813±0.077比1.097±0.056, F=75.485, P<0.01;0.902±0.030比1.231±0.123, F=52.224, P<0.01;1.089±0.044比1.283±0.049, F=85.388, P<0.01;1.218±0.008比1.673±0.139, F=33.825, P<0.05;0.463±0.025比0.875±0.013, F=447.19, P<0.01);bax、Caspase-3相对表达量高于PAH组(1.188±0.072比0.738±0.048, F=63.635, P<0.01;1.750±0.028比1.432±0.017, F=31.684, P<0.01)。治疗组α-SMA、PCNA荧光强度低于对照组。结论藻蓝蛋白可通过抑制肺血管胶原沉积, 减少炎性因子表达, 抑制细胞增殖, 促进凋亡, 减轻大鼠PAH肺血管重构。Objective To investigate the mechanism of phycocyanin improving pulmonary vascular remodeling in rats with pulmonary arterial hypertension(PAH).Methods We randomly divided 30 male Sprague-Dawley(SD)rats into 3 groups:normal control group,PAH group,and phycocyanin treatment group,with 10 rats in each group.The PAH model was induced by intraperitoneal injection of monocrotaline(MCT).The treatment group was given phycocyanin by gavage on the 15th day.Effects on right ventricular systolic blood pressure(RVSP)and right ventricular hypertrophy index(RVHI)were examined.The changes of pulmonary vessels were examined by hematoxylin-eosin(HE)and Masson staining.The expression of transforming growth factor-β1(TGF-β1),nuclear factor kappa-B(NF-κB),B-cell lymphoma-2(bcl-2),cysteinyl aspartate-specific protease(Caspase)-3,α-smooth muscle actin(α-SMA)and proliferating cell nuclear antigen(PCNA)was detected by Western blotting.The expression ofα-SMA and PCNA was evaluated by immunofluorescence.Statistical significance was determined by one-way ANOVA.Results RVSP and RVHI in the treatment group were lower than in the PAH group[(24.60±3.33)mmHg vs.(40.49±3.76)mmHg,F=140.998,P<0.01;(32.23±2.99)%vs.(43.45±3.10)%,F=90.774,P<0.01].The percentage of pulmonary arteriole media thickness and media area decreased in the treatment group and pulmonary vascular collagen deposition decreased after treatment(0.579±0.013 vs.0.736±0.023,F=251.494,P<0.01;0.574±0.063 vs.0.917±0.036,F=84.346,P<0.05;(9.81±0.66)%vs.(23.23±2.05)%,F=294.181,P<0.01).The expression levels of TGF-β1,bcl-2,α-SMA,PCNA and phosphorylated NF-κB(p-NF-κB)/NF-κB were suppressed whereas bcl-2 associated X protein(bax)and Caspase-3 were elevated in the treatment group(0.813±0.077 vs.1.097±0.056,F=75.485,P<0.01;0.902±0.030 vs.1.231±0.123,F=52.224,P<0.01;1.089±0.044 vs.1.283±0.049,F=85.388,P<0.01;1.218±0.008 vs.1.673±0.139,F=33.825,P<0.05;0.463±0.025 vs.0.875±0.013,F=447.19,P<0.01;1.188±0.072 vs.0.738±0.048,F=63.635,P<0.01;1.750±0.028 vs.1.432±0.017

关 键 词：藻蓝蛋白 肺动脉高压 肺血管重构 炎性反应 细胞增殖 

分 类 号：R725.4[医药卫生—儿科]