川芎嗪对支气管肺发育不良新生大鼠缺氧诱导因子通路表达的影响

目的：观察川芎嗪对新生大鼠支气管肺发育不良的防治作用并探讨其可能的作用机制。方法：选取80只足月新生12h内的sD大鼠，随机分成4组，每组20只。A组：空气对照组；B组：空气±川芎嗪组；C组：高氧对照组（FiO：=60％）；D组：高氧±川芎嗪组。B、D组予以川芎嗪30mg／kg连续给药14d。每组选取8只，计算肺湿重／干重（W／D）、肺放射状肺泡计数（RAC）；免疫组织化学方法检测PECAM—l的表达水平并计算肺微血管密度（yvc）；RT—PCR方法检测HIF—1α及VEGFmRNA水平；免疫组织化学染色法检测HIF-1α及VEGF蛋白水平。结果：c组肺泡及肺血管发育明显受到抑制，肺W／D值升高，RAC、MVC值较A组和B组均明显减少W／D：（5．64±0．31）粥（4．92±0．19）、（4．91±0．06）；RAC值：（4．75±0．71）销（9．00±0．76）、（9．03±0．76）；MVC：（45．30±2．05）∞（48．70±0．83）、（48．60±1．49），P〈0．05]；C组肺组织HIF—1α、VEGF表达较A组明显减少，D组肺组织HIF一1α、VEGF表达较c组有所增加，差异均有统计学意义（P〈0．05）。结论：川芎嗪对新生鼠支气管肺发育不良有一定的防治作用，其机制可能与川芎嗪激激活HIF一1α—VEGF通路，从而改善肺泡和肺微血管发育有关。

Tetramethylpyrazine Alleviating Bronchopulmonary Dysplasia in Neonatal Rats by Activating the Hypoxia- inducible Factor Signaling Pathway

Objective： To investigate the effect of tetramethylpyrazine on bronchopulmonary dysplasia in neonatal rats. Methods： Eighty Sprague-Dawley （SD） neonatal rats, which were less than twelve hours old, were enrolled in this study. The neonatal rats were randomly divided into four groups. Group A： air-exposed control group; Group B： air-exposed ± tetramethylpyrazine-treated group; Group C ： hyperoxia-exposed control group （ FiO2 = 60% ） ; Group D ： hyperexia-exposed ± tetramethylpyrazine-treated group. The neonatal rats of group B and group D were intraperitoneally injected with tetramethylpyrazine 30 mg/（ kg d） in solution of normal saline （NS） for 14 days. Eight rats of each group were randomly chosen and killed, the ratio of wet/dry （W/D） weight of lung and the radical alveolar count （ RAC ） was measured ; the micro vessel count （ MVC ） was counted by the expression of PECAM-1 by immunostaining. Immunostaining and RT-PCR were used to detect the changes of expression. Results： Group C showed the oxygen sensor hypoxia-inducible factor （HIF-lot） was inhibited and the vascular endothelial growth factor （VEGF） of lung and vascular were developed. Compared to group A and group B, MVC and RAC in group C decreased dramatically W/D ： （ 5.64 ± 0. 31 ） vs （4.920.19） and （4.910.06）; RAC： （4.750.71） vs （9.000.76） and （9.030.76）;MVC： （45.302.05） vs （48.70±0.83） and （48. 60 ± 1.49）, P〈O.05]. The expression of HIF-la and VEGF was dramatically decreased in group C eompare with group A （P〈0.05）. Conclusions： Tetramethylpyrazine may partially prevent BPD induced by hyperoxia through activating the hypoxia-indueible factor signaling pathway.