Role and mechanism of L-thyroxine on brain tissue hypoxia-inducible factor 1α expression in neonatal rats with hypoxia-ischemia brain damage / 中华实用儿科临床杂志

ABSTRACT

Objective To observe the expression of hypoxia-inducible factor 1 α (HIF-1α) in rat brain after hypoxia-ischemia(HI),and to explore the possible mechanism of L-thyroxine (L-T4) on HIF-1α expression.Methods Sixty-four postnatal 7-day Sprague-Dawley rats were randomly divided into 4 groups:the sham operation group,HI group,menstruum-treated group and L-T4-treated group.HIBD models were generated according to Rice model method.The rats in menstruum-treated group and L-T4-treated group were respectively administrated of intraperitoneal injection of menstruum with the equal volume and 2 μg/100g L-T4,once a day,for 5 days.The expressions of HIF-1α and phospho-protein kinase B(p-Akt) protein were detected by means of immunohistochemistry.Reverse transcription-polymerase chain reaction was used to detect the level of HIF-1α mRNA.Results The levels of p-Akt protein(50.168 ±4.259),HIF-1α protein (72.795 ±6.121) and HIF-1α mRNA (0.448 ± 0.035) were upregulated compared with those in the sham operation group (8.080 ±0.369,38.581 ± 2.846,0.174 ± 0.015),and the differences were significant (all P ＜ 0.05).The levels of p-Akt protein (82.765 ± 6.271),HIF-1 α protein (117.350 ± 9.374) and HIF-1 α mRNA (0.618 ± 0.042) in L-T4-treated group were higher than those in HI group,and the differences were significant (all P ＜ 0.05).The level of HIF-1 α protein was positively correlated with p-Akt protein in HI group and L-T4-treated group [r(HI) =0.635,P=0.048;r(L-T4) =0.694,P=0.026].Conclusions L-T4 can upregulate HIF-1α mRNA and protein expression in neonatal rats with hypoxia-ischemia brain damage.Phosphatidylinositol-3-kinase/protein kinase B signaling pathway may be involved in L-T4 upregulating HIF-1α mRNA and protein expression.