机构地区:[1]呼吸疾病国家重点实验室(广州医学院广州医科大学)广州呼吸健康研究院广州医科大学附属第一医院,510120 [2]广州医科大学附属第二医院呼吸内科,510260 [3]河南省人民医院呼吸与危重症医学科,郑州450003
出 处:《国际呼吸杂志》2018年第16期1236-1242,共7页International Journal of Respiration
基 金:广东省高校创新强校工程(Q17024061);广东省自然科学基金博士启动项目(2017A030310552);国家自然科学基金青年科学基金(81700048);广东省科技计划项目-公益研究与能力建设专项(2017A020215114);广东省自然科学基金自由申请项目(2016A030313606);广州市教育局市属高校科研项目(青年项目)(1201630095)
摘 要:目的探讨丹参酮ⅡA磺酸钠(STS)是否通过骨形态发生蛋白4(BMP4)降低慢性低氧诱导升高的肺动脉平滑肌细胞(PASMCs)中活性氧(ROS)水平,并最终达到治疗慢性低氧性肺动脉高压(CHPH)的作用。方法30只SD大鼠按随机数字法分为常氧对照组、CHPH组和CHPH+STS组。CHPH模型成功建立后,采用右心室测压法检测大鼠右心室收缩压(RVSP)并计算右心肥厚指数ERV/(LV+S)];Western blot法检测远端肺动脉平滑肌组织(PA)中前体和成熟BMP4的表达;收集各组PA,胶原酶消化法培养大鼠原代PASMCs,72h后用流式细胞术检测各组PASMCs中ROS水平。结果与常氧对照组相比,CHPH组大鼠RVSP及RV/(LV+S)分别升高至(55.74±4.95)mmHg(1mmHg=0.133kPa)和(0.48±0.021),差异具有统计学意义(t=-24.03、-34.28,P值均〈0.05);而CHPH+STS组RVSP及RV/(LV+S)分别为(36.28±5.65)mmHg和(0.37±0.021),表明STS可有效降低CHPH大鼠模型中RVSP和RV/(LV+S),差异具有统计学意义(t=-16.26、-17.34,P值均〈0.05)。CHPH大鼠模型组PA中前体、成熟BMP4于常氧对照组的相对表达量分别为(157.09±29.33)%、(196.14±62.13)%;而CHPH+STS组PA中前体、成熟BMP4于常氧对照组的相对表达量分别为(101.13±16.46)%、(88.21±19.51)%,结果显示STS可显著下调缺氧诱导升高的BMP4,差异具有统计学意义(t=3.10、-3.09,P值均〈0.05)。常氧对照组PASMCs中ROS水平为(29.4±1.90)%,CHPH大鼠模型组ROS水平为(55.00±6.41)%,慢性低氧诱导PASMCs中ROS升高,差异具统计学意义(t=-16.11,P〈0.05);而CHPH+STS组ROS水平为(35.07±3.69)%,STS可下调慢性低氧诱导增加的PASMCs中ROS水平,差异具有统计学意义(t=8.53,P〈005)。结论STS显著降低CHPH模型大鼠的RVSP、RV/(LV+S)和PObjective To investigate whether bone morphogenetic protein 4 (BMP4) mediate sodium tanshinone ⅡA sulfonate (STS)-induced downregulation of reactive oxygen species (ROS) level in pulmonary artery smooth muscle cells (PASMCs). Methods Thirty rats randomly divided into normoxia control group, chronic hypoxia-induced pulmonary hypertension (CHPH) group and CHPH + STS group. Twenty-one days later, right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index [RV/(LV+S)3 were measured, pro BMP4 and Mature-BMP4 protein expression in rat pulmonary artery smooth muscle (PA) were detected by Western blot, we also culture primary PSAMCs in these three groups for analyzing the ROS levels in PASMCs. Results RVSP and RV/(LV+S) in normoxia control group, CHPH group and CHPH + STS group were respectively (26.34 ± 3.12) mmHg (1 mmHg = 0. 133 kPa), (0.27±0.033) ; (55.7±4.95) mmHg, (0.48±0.021) and (36.28±5.65) mmHg, (0.37± 0. 021). Results showed RVSP and RV/(LV+S) were significantly increased in hypoxia condition ( t = -24.03,-34.Z8, both P 〈0.05), and STS lowered hypoxia-upregluted RVSP and RV/(LV+ S) in CHPH rat model (t =-16.26,-17.34, both P 〈0.05). The expression of pro BMP4 and mature- BMP4 protein in pulmonary artery smooth muscle of CHPH group were ( 157.09± 29.33) % and ( 196.14±62.13) %, higher than normoxia control group which were (100± 0)% and (100±0)%. However, in the CHPH+ STS group pro-BMP4 and mature-BMP4 protein expression were recovered to (101.13±16.46)%0 and (88.21±19.51)%,(t =-3.10, 3. 09, both P 〈0. 05) . The level of ROS in PASMCs of CHPH group increased from (29.4± 1.90)% (normoxia control group) to (55.00±6.41)%, (t = -16.11, P 〈0.05). In CHPH--STS treated rats, the level of ROS was (35.07± 3.69) %, statistically different from CHPH group ( t= 8.53, P 〈0.05). Conclusions STS markedly decreased RVSP, RV/ (LV+S�
关 键 词:丹参酮ⅡA磺酸钠 慢性低氧性肺动脉高压模型 骨形态发生蛋白4 活性氧
分 类 号:R544.1[医药卫生—心血管疾病]
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