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山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (8): 28-33.

• 基础医学 • 上一篇    下一篇

法舒地尔对野百合碱诱导肺动脉高压大鼠骨形态蛋白受体表达的影响

王春晓,夏伟,李福海,武志华   

  1. 山东大学齐鲁医院儿科, 济南 250012
  • 收稿日期:2012-12-27 出版日期:2013-08-10 发布日期:2013-08-10
  • 通讯作者: 夏伟,E-mail:cicql@163.com

Effect of fasudil on the expression of BMPR in rats with monocrotalineinduced pulmonary arterial hypertension

WANG Chun-xiao, XIA Wei, LI Fu-hai, WU Zhi-hua   

  1. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2012-12-27 Online:2013-08-10 Published:2013-08-10

摘要:

目的   通过观测法舒地尔在野百合碱(MCT)诱导肺动脉高压(PAH)大鼠肺血管结构重构过程中对骨形态蛋白受体(BMPR)表达的影响,探讨法舒地尔改善MCT诱导肺血管结构重构的机制。方法   4周龄Wistar大鼠60只随机分为早/晚期正常对照组、早/晚期肺动脉高压对照组、早/晚期治疗组,每组10只。皮下注射MCT建立大鼠PAH模型,早期治疗组在注射MCT 1周后应用法舒地尔治疗,8周结束;晚期治疗组在第9周开始治疗,12周结束。图像分析系统测定肺小动脉管壁厚度占外径的百分比(WT%)和管壁面积占血管总面积的百分比(WA%);实时荧光定量PCR检测肺动脉中BMPR1A、BMPR2基因表达量,Western blotting检测BMPR1A、BMPR2蛋白以及磷酸化肌球蛋白磷酸酶靶蛋白1(pMYPT1)的表达。结果   早/晚期肺动脉高压对照组WT%和WA%分别较早/晚期正常对照组显著增高(P<0.05),法舒地尔治疗后,早/晚期治疗组WT%和WA%分别较早/晚期肺动脉高压对照组显著降低(P<0.05),且晚期肺动脉高压治疗组明显低于早期肺动脉高压治疗组(P<0.05)。PCR及Western blotting结果显示,BMPR1A及BMPR2基因和蛋白在早∕晚期肺动脉高压对照组中的表达量均分别明显低于早∕晚期正常对照组(P<0.05),法舒地尔治疗后,早∕晚期治疗组中的表达量均显著增高(P<0.05)。pMYPT1蛋白在早∕晚期肺动脉高压对照组中较正常对照组明显增高(P<0.05),法舒地尔治疗后,其表达在早∕晚期治疗组均显著降低(P<0.05)。结论   法舒地尔通过上调骨形态蛋白受体基因、蛋白表达,抑制并逆转MCT诱导肺动脉高压大鼠肺血管重构中平滑肌细胞的增殖。

关键词: 法舒地尔;高血压,肺性;骨形态蛋白受体;肺血管重构

Abstract:

Objective   To explore the mechanism of fasudil improving MCT-induced PAH by studying the effect of fasudil on the expression of bone morphogenetic protein receptor (BMPR) in rat of monocrotaline (MCT)-induced pulmonary arterial hypertension. Methods   A total of 60 healthy Wistar rats of 4 weeks old were randomly divided into 6 groups: the early normal control group, the early model control group, the early fasudil group, the later normal control group, the later model control group, the later fasudil group. The ratios of arteriole wall thickness to vascular external diameter (WT%), and vascular area to total vascular area (WA%) were measured by a computerized image analyzer. The gene expression of BMPR1A and BMPR2 was determined by SYBGREEN RT-PCR. The protein expression of BMPR1A, BMPR2 and phosphorylated myosin phosphatase target protein-1(p-MYPT1)was determined by Western blotting. Results   Compared with the early/later normal control groups, the WT% and WA% increased significantly in the early/later model control groups(P<0.05). After treated with fasudil, the WT% and WA% in the early/later model control groups was lower than that of the early/later normal control groups(P<0.05). And in the later model control groups, the WT% and WA% obviously decreased compared with that of the early model control groups(P<0.05). The gene and protein expression of BMPR1A, BMPR2 were lower in the early/later model control groups than that in the early/later normal control groups revealed by PCR and Western blotting(P<0.05). After the treatment with fasudil, the WT% and WA% in the early/later fasudil groups increased significantly(P<0.05). The expression of p-MYPT1 makeredly elevated in the early/later model control groups compared to that in the early/later normal control groups(P<0.05). After treated wih fasudil, it decreased in the early/later fasudil groups(P<0.05). Conclusion   Fasudil can inhibit and reverse the pulmonary artery smooth muscle proliferation of MCT-induced pulmonary artery remodeling in PAH in rats effectively by upregulating mRNA and protein expressions of BMPR.

Key words: Fasudil; Hypertension, pulmonary; Bone morphogenetic protein receptor; Pulmonary vascular remodeling

中图分类号: 

  • R363
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[2] 倪世容1,王万铁1,王鑫2,郝卯林1,戴雍月1 . 人硫氧还蛋白对大鼠肺缺血再灌注损伤时细胞凋亡及ASK1的影响[J]. 山东大学学报(医学版), 2010, 48(7): 19-.
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