The expression of HIF-1 α in liver tissues in the rat model of paraquat poisoning

Abstract

Objective To observe the levels of HIF-α and TGF-β in the liver tissue,change of serum transaminase in different phases after paraquat (PQ) toxicity and liver histopathology change in PQinduced liver toxicity of rats models in order to analyze the relationship between HIF-1 α and hepatic toxicity induced by PQ.Methods A total of 48 healthy SD rats were randomly (random number) assigned into 2 groups:PQ poisoning group (n =42,20％ PQ solution,50 mg/kg in 1mL) and control group (n =6,normal saline 1mL).Rats were separately sacrificed and liver tissue samples were harvested at 2,6,12,24,48,72 h and 120 h after PQ administered by gastric lavage.Arterial blood gas (ABG) analysis and serum alanine transaminase were assayed.Liver tissue HE and Masson staining and immunochemistry changes were also investigated.HIF-1α and TGF-β levels were detected by Western blot technique.Results Lactic acid level was significantly higher in PQ group than that in control group at 6 h after PQ exposure (P ＜ 0.05).The level of serum alanine transaminase was increased and significantly higher if PQ group than that in control group at 2 h after PQ poisoning (P ＜ 0.05).The level of HIF-1 α and TGF-β protein in the liver tissue were up-regulated significantly and higher in PQ group than those in control group at 2 h after PQ exposure (P ＜ 0.05).The hepatocytes necrosis and inflammatory cells infiltration were observed around portal area 2 h after PQ poisoning.At 12 h after PQ exposure,the periportal area filled with necrosis of hepatocytes and the necrosis began to extend,and huge amounts of inflammatory cell infiltration were found.Cord-like fibroplasia was found.All the histological changes were around central portal area and were enlarged gradually.Conclusions The results show that there are increased level of HIF-1 α in the early stage of PQ poisoning rats.The liver fibroplasia may be associated with increasing the level of TGF-β promoted by HIF-1α. Key words: Paraquat; Poison ; Hypoxemia; Acute liver injury; Hypoxia-inducible factor-1 alpha (HIF-1α) ; Transforming growth factor beta (TGF-β)