Role and mechanism of L-thyroxine on brain tissue hypoxia-inducible factor 1α expression in neonatal rats with hypoxia-ischemia brain damage

Abstract

Objective To observe the expression of hypoxia-inducible factor 1α(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-polyme-rase 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-1α protein (117.350±9.374)and HIF-1α 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-1α 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. Key words: Hypoxia-inducible factor 1α; L-thyroxine; Hypoxia-ischemia brain damage; Rat, newborn