热休克蛋白70对缺氧性肺动脉高压新生大鼠肺血管重塑的作用研究

Effect of heat shock protein 70 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension

目的探讨热休克蛋白70(HSP70)对缺氧性肺动脉高压(HPH)新生大鼠肺动脉压力及肺血管重塑的作用。方法将128只Wistar新生大鼠按随机数字表法分为HPH模型组和空白对照组,根据转染液不同将HPH组再分为盐水组、空病毒组(标有绿色荧光信号但未携带目的基因的病毒载体)和病毒+HSP70组(标有绿色荧光信号同时携带目的基因的病毒载体)。以吸入8%氧浓度的氮氧混合气(1.5 L/min)建立HPH模型,并分别于缺氧3、7、10、14 d检测各组新生大鼠的肺动脉压力(m PAP)及肺血管重塑指标(MT%、MA%)。结果缺氧3、7、10 d时,盐水组和空病毒组HSP70表达较空白对照组增强(P<0.01),病毒+HSP70组HSP70表达均高于空白对照组、盐水组和空病毒组(P<0.01),缺氧14 d时各组间HSP70表达差异无统计学意义(P>0.05)。缺氧3、7、10 d时,盐水组和空病毒组新生大鼠m PAP持续增高,且均高于空白对照组(P<0.05),病毒+HSP70组新生大鼠m PAP与空白对照组比较未见明显增高(P>0.05);缺氧14 d时,盐水组、空病毒组、病毒+HSP70组新生大鼠m PAP比较差异无统计学意义(P>0.05),但均明显高于对照组(P<0.05)。缺氧7 d后盐水组和空病毒组MT%、MA%明显高于空白对照组(P<0.05),病毒+HSP70组较对照组差异无统计学意义(P>0.05);缺氧14 d时,盐水组、空病毒组、病毒+HSP70组MT%、MA%比较差异无统计学意义(P>0.05),但均明显高于对照组(P<0.05)。结论 HSP70可能可以降低HPH新生大鼠肺动脉压力,减轻其肺血管重塑。

Objective To investigate the effect of heat shock protein 70（HSP70） on pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension（HPH）. Methods A total of 128 Wistar neonatal rats were randomly divided into HPH model and blank control groups. According to the transfection solution, the HPH model group was further divided into normal saline group, empty virus group（viral vectors marked with a green fluorescent signal and not carrying the target gene）, and virus＋HSP70 group（viral vectors marked with a green fluorescent signal and carrying the target gene）. The HPH model was established by inhalation of nitrogen-oxygen mixture（1.5 L/minutes and 8% oxygen）. Pulmonary arterial pressure（m PAP） and the indicators of pulmonary vascular remodeling（MT% and MA%） were measured on days 3, 7, 10, and 14 of hypoxia. Results On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups had significantly enhanced expression of HSP70 compared with the blank control group（P〈0.01）, and the virus＋HSP70 group had significantly higher expression of HSP70 than the blank control, normal saline, and empty virus groups（P〈0.01）. On day 14 of hypoxia, the expression of HSP70 showed no significant difference between these groups（P〉0.05）. On days 3, 7, and 10 of hypoxia, the normal saline and empty virus groups showed continuous increases in m PAP compared with the blank control group（P〈0.05）. There was no significantdifference in m PAP between the virus＋HSP70 and blank control groups（P〈0.05）. On day 14 of hypoxia, there was no significant difference in m PAP among three subgroups of the HPH model group（P〈0.05）, but the m PAP in the three subgroups was significantly higher than in the blank control group（P〈0.05）. After 7 days of hypoxia, the normal saline and empty virus groups showed significantly higher MT% and MA% than the blank control group（P〈0.05）, but the two indicators showed no significant differences between the virus＋HSP70 and the blank control groups（P〈0.05）. On day 14 of hypoxia, there were no significant differences in MT% and MA% among three subgroups of the HPH model group（P〈0.05）, but the MT% and MA% in the three subgroups were higher than in the blank control group（P〈0.05）. Conclusions HSP70 may reduce pulmonary arterial pressure and pulmonary vascular remodeling in neonatal rats with HPH.