The effects of hypoxia on the expression of inflammatory factor high mobility group box-l in the pulmonary arteriolae of neonatal SD rats

Abstract

Objective To study the effects of hypoxia on the expression of inflammatory factor high mobility group box-l (HMGB1) in the pulmonary arteriolae of neonatal SD rats. Method A total of 80 neonatal SD rats were randomly assigned into control group and hypoxia-induced persistent pulmonary hypertension of the newborn model (PPHN) group. The PPHN group was subdivided into 2 h, 8 h, 24 h, and 3 d post-PPHN subgroups according to the time of sacrifice. PPHN model was established on postnatal day 4 when rat pups in PPHN group were kept in low-oxygen box (10% O2 and 90% N2) for consecutively 7 days. Multi-channel physiological transducer RM-6280 was used recording the mean pulmonary artery pressure (mPAP) at the root to pulmonary artery of rat pups. ELISA method was used examining the serum level of HMGB1 of rat pups in each group. The pathology of the lung tissue was studied using optical microscope after HE staining, and MIAS-2000 medical image analysis software was used to calculate the ratio of the middle membrane thickness to the outer diameter of the pulmonary arteriolae wall (MT%). Protein level of HMGB1 in the lung was examined using Western Blot. Result The lung pathology in PPHN rats showed thickening of the middle membrane of the pulmonary arteriolae wall and stenosis of the pulmonary arteriolae. MT% of control group and PPHN group were 5.3% (3.7%, 7.6%) and 7.1% (4.6%, 9.2%), respectively, without significant differences (P>0.05). At 2 h, 8 h, 24 h, 3 d post-PPHN timepoints, the serum levels of HMGB1 in PPHN group were (13.2±3.1), (15.4±3.6), (17.1±3.5), and (15.8±3.6) ng/ml, respectively, without intra-subgroup differences (F=2.134, P>0.05), but significant differences existed when compared with control group at each timepoint (P 0.05). Conclusion HMGB1 is closely related with the pathogenesis of PPHN, indicating the inflammatory response plays an important role in the mechanisms of PPHN. HMGB1 may be an indicator for the assessment of hypoxia-induced PPHN. Key words: Anoxia; Pulmonary hypertension; High mobility group proteins; Rats