Objective: To observe the pathological changes of renal tissue in the rats with paraquat (PQ) poisoning as well as the serum creatinine (SCr) levels and expression levels of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β (TGF-bgr;) in renal tissue at different time points after PQ poisoning, and to investigate the association of HIF-1α with renal injury after PQ poisoning.
Methods: Forty-eight healthy male Sprague-Dawley rats were randomly divided into control group (n = 6) and PQ group (n = 42). The control group was given a single dose of 1 ml saline by gavage; the PQ group was given a single dose of 1 ml PQ (50 mg/kg), which was prepared by diluting 20% raw liquid of PQ with saline, by gavage. The PQ group was further divided into 2, 6, 12, 24, 48, 72 and 120 h PQ subgroups (n = 6 for each subgroup) to be examined at 2, 6, 12, 24, 48, 72, or 120 h after gavage. Their arterial blood was collected for blood gas analysis as well as blood lactic acid (BLA) and SCr measurement; renal sections were subjected to HE staining; the protein expression of HIF-1α and TGF-β in renal tissue was measured by Western blot.
Results: The BLA level and SCr level began to rise at 6h after poisoning. Compared with the control group, the 6, 12, 24, 48, 72 and 120 h PQ subgroups had significantly increased BLA and SCr levels (P < 0.05); the 72 and 120 h PQ subgroup showed hypoxemia (P < 0.05). The protein expression of HIF-1α in PQ group increased significantly at 6h and reached the peak level at 72 h, with a significant difference from that in the control group at 6, 12, 24, 48, 72, and 120 h (P < 0.05). The protein expression of TGF-β in PQ group began to rise at 24 h, reached the peak level at 72 h, and declined at 120 h, with a significant difference from that in the control group at 24, 48, and 72 h (P < 0.05). The protein expression of HIF-1α was positively correlated with SCr level (r = 0.9308, P = 0.0008), uncorrelated with arterial partial pressure of oxygen (r = -0.6996, P = 0.0534), and positively correlated with BLA level (r = 0.9483, P = 0.0003). The pathological changes of renal tissue mainly included the degeneration and necrosis of renal tubular epithelial cells, which worsened as the time went on and appeared less severe at 120 h.
Conclusion: The HIF-1α expression in renal tissue increases significantly in the early stage of PQ poisoning, which is associated with increased BLA and SCr levels and causes upregulated expression of TGF-β that promotes renal fibrosis.