Anti-placental growth factor antibody ameliorates hyperoxia-mediated impairment of lung development in neonatal rats

This study investigates the effect of the overexpression of the placental growth factor (PGF) and hyperoxia on lung development and determines whether anti-PGF antibody ameliorates hyperoxia-mediated impairment of lung development in newborn rats. After exposure to normoxic conditions for seven days, newborn rats subjected to normoxia were intraperitoneally or intratracheally injected with physiological saline, adenovirus-negative control (Ad-NC), or adenovirus-PGF (Ad-PGF) to create the Normoxia, Normoxia+Ad-NC, and Normoxia+Ad-PGF groups, respectively. Newborn rats subjected to hyperoxia were intraperitoneally injected with physiological saline or anti-PGF antibodies to create the Hyperoxia and Hyperoxia+anti-PGF groups, respectively. Our results revealed significant augmentation in the levels of PGF and its receptor Flt-1 in the lung tissues of newborn rats belonging to the Normoxia+Ad-PGF or Hyperoxia groups. PGF overexpression in these groups caused lung injury in newborn rats, while anti-PGF antibody treatment significantly cured the hyperoxia-induced lung injury. Moreover, PGF overexpression significantly increased TNF-α and Il-6 levels in the bronchoalveolar lavage (BAL) fluid of the Normoxia+Ad-PGF and Hyperoxia groups. However, their levels were significantly reduced in the BAL fluid of the Hyperoxia+anti-PGF group. Immunohistochemical analysis revealed that PGF overexpression and hyperoxia treatment significantly increased the expression of the angiogenesis marker, CD34. However, its expression was significantly decreased upon administration of anti-PGF antibodies (compared to the control group under hyperoxia). In conclusion, PGF overexpression impairs lung development in newborn rats while its inhibition using an anti-PGF antibody ameliorates the same. These results provided new insights for the clinical management of bronchopulmonary dysplasia in premature infants.

本研究探讨了胎盘生长因子（placental growth factor, PGF）过表达与高氧环境对新生大鼠肺发育的影响，并明确抗PGF抗体是否可改善高氧介导的新生大鼠肺发育损伤。将新生大鼠置于常氧环境中培养7天后，分别向其腹腔或气管内注射生理盐水、腺病毒阴性对照（adenovirus-negative control, Ad-NC）或腺病毒-PGF（adenovirus-PGF, Ad-PGF），以此分别构建常氧组、常氧+Ad-NC组以及常氧+Ad-PGF组；将另一部分新生大鼠置于高氧环境中，分别腹腔注射生理盐水或抗PGF抗体，以此构建高氧组与高氧+抗PGF组。研究结果显示，常氧+Ad-PGF组与高氧组新生大鼠肺组织中PGF及其受体Flt-1的表达水平显著升高。上述两组中PGF过表达可引发新生大鼠肺损伤，而抗PGF抗体治疗可显著缓解高氧诱导的肺损伤。此外，常氧+Ad-PGF组与高氧组新生大鼠支气管肺泡灌洗液（bronchoalveolar lavage, BAL）中肿瘤坏死因子-α（TNF-α）与白细胞介素-6（IL-6）的水平显著升高；而高氧+抗PGF组的上述细胞因子水平则显著降低。免疫组化分析结果表明，PGF过表达与高氧处理可显著提升血管生成标志物CD34的表达水平，但抗PGF抗体给药可显著下调该标志物的表达（相较于高氧环境下的对照组）。综上，PGF过表达会损伤新生大鼠的肺发育，而通过抗PGF抗体抑制PGF则可改善该损伤。本研究结果为早产儿支气管肺发育不良的临床管理提供了新的思路。