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[肝细胞生长因子对肺动脉高压大鼠的干预及对内皮细胞膜微粒的影响]

[Hepatocyte growth factor intervention on rats with pulmonary hypertension and effect of endothelial cell membrane microparticles].

作者信息

Liu Zhenjun, Zhang Rujun, Yang Yu, Wang Junxian, He Zhongkai, Chen Jianying

机构信息

Department of Cardiology,Affiliated Hospital of Guangdong Medical College,Zhanjiang 524001, China.

Email:

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2014 Jun;37(6):433-6.

Abstract

OBJECTIVE

To explore the effect of transfection of adenovirus carrying hepatocyte growth factor (HGF) on pulmonary arterial hypertension (PAH) and endothelial cell membrane microparticles (EMP) in a rat model, and the underlying mechanism.

METHODS

Forty healthy male SD rats were randomly divided into four groups, the normal control group (NOR group), monocrotaline (MCT)-induced pulmonary hypertension group (PAH group), HGF treatment of PAH group (HGF group and THGF group) each with 10 rats. NOR group and the PAH Group: intratracheal instillation of 0.2 ml PBS solution; HGF group: intratracheal instillation of 0.2 ml HGF one times; THGF Group: intratracheal instillation of 0.2 ml HGF one times, and then 1 week repeat again. Different interventions after 2 weeks, the rats was measured mean pulmonary arterial pressure, right ventricular hypertrophy index calculation, HE staining index of pulmonary arterial wall thickness, area index, plasma levels of endothelial cell microparticles.

RESULTS

HGF intratracheal instillation after 2 weeks, HGF and THGF groups of SD rats mPAP, RVHI, TI, AI decreased significantly compared with PAH group (P < 0.05). PAH group was increased in particulate levels at different time points significantly higher levels of horizontal (P < 0.05). The EMP levels in HGF group which at 7 and 14 days after dosing were significantly decreased compared with PAH.It still higher than the NOR group (P < 0.05). And after administration of 7 days, 14 days, the EMP level of HGF group was significantly lower than before administration (P < 0.05).

CONCLUSIONS

Thought airway instillation transfected HGF, pulmonary artery pressure can reduce greater degree, but can't achieve complete reversal. It can inhibit the pulmonary artery wall thickening and maintain effective lumen area, delaying the right ventricular hypertrophy by reducing the membrane particles within the lung, thereby promoting endothelial cell repair to achieve the goal of intervention in pulmonary hypertension.

摘要

目的

探讨携带肝细胞生长因子(HGF)的腺病毒转染对大鼠模型肺动脉高压(PAH)及内皮细胞膜微粒(EMP)的影响及其潜在机制。

方法

将40只健康雄性SD大鼠随机分为四组,正常对照组(NOR组)、野百合碱(MCT)诱导的肺动脉高压组(PAH组)、HGF治疗PAH组(HGF组和THGF组),每组10只。NOR组和PAH组:气管内滴注0.2 ml PBS溶液;HGF组:气管内滴注0.2 ml HGF一次;THGF组:气管内滴注0.2 ml HGF一次,然后1周后重复一次。2周后进行不同干预,测量大鼠平均肺动脉压、计算右心室肥厚指数、HE染色检测肺动脉壁厚度指数、面积指数、血浆内皮细胞微粒水平。

结果

气管内滴注HGF 2周后,HGF组和THGF组SD大鼠的平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)、厚度指数(TI)、面积指数(AI)较PAH组显著降低(P<0.05)。PAH组不同时间点微粒水平均显著高于其他组水平(P<0.05)。给药后7天和14天,HGF组的EMP水平较PAH组显著降低,但仍高于NOR组(P<0.05)。且给药后7天、14天,HGF组的EMP水平显著低于给药前(P<0.05)。

结论

经气道滴注转染HGF后,肺动脉压可较大程度降低,但不能完全逆转。它可抑制肺动脉壁增厚,维持有效管腔面积,通过减少肺内膜微粒延缓右心室肥厚,从而促进内皮细胞修复,达到干预肺动脉高压的目的。

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