Intermittent Hypoxia Induced Kidney Injury In Rats And Effect On TLR4 Expression In The Kidney

Objective: In this study,an intermittent hypoxia(IH)rat model was established to simulate obstructive sleep apnea hypopnea syndrome(OSAHS).To research the effect of obstructive sleep apnea-hypopnea syndrome on kidney injury and the expression of Toll-like receptor 4(TLR4)in the kidney in rats.For clinical evaluation of OSAHS patients and prevention and treatment of OSAHS-related kidney diseases provide new ideas.Methods: First,a rat model of intermittent hypoxia was established.Thirty-two SPF male Wistar rats were randomly divided into four groups.Eight in group A(normal control group,oxygen concentration 21%),eight in group B(mild intermittent hypoxia group,oxygen concentration 15%),eight in group C(moderate intermittent hypoxia group,oxygen concentration 9%),eight in group D(severe intermittent hypoxia group,oxygen concentration 6%).The rats in the intermittent hypoxia group were put into the experimental chamber and cyclically filled with nitrogen and oxygen.The time required for one cycle was 120 S,and the intermittent hypoxia time was 8 hours per day.The rats in group A were exposed to the air and didn’t give any special way to deal with.Rats in each group were equally fed.The rats were killed after 5 weeks of intermittent hypoxia.The kidney tissues of the rats were stained with Hematoxylin-eosin(HE)and the pathological structure of the kidneys was observed under a microscope.Changes in the expression of TLR4 protein in kidney tissue were detected by immunohistochemistry.And we analyze the results finally.Results:(1)HE staining: Mice in group A(blank control group)showed almost normal glomerular and tubular structures,The renal tissues of group B rats showed slight narrowing of the renal tubule lumen,a small amount of red blood cells in the glomerular capillaries,a slight swelling of the renal tubular epithelial cells,and a slight disorder of the renal tubular structure.In renal tissues of groups C and D,glomerular capillary hyperemia was evident,the lumen of the renal tubules was severe narrowed,and the cytoplasm was lightly stained,especially near the curved tubules.The renal tubular structure was disordered.(2)Immunohistochemistry: Compared with group A,the expression of TLR4 protein in renal tubular epithelial cells of rats in groups B,C and D was significantly increased.The difference was statistically significant(P<0.05).And the expression of TLR4 protein gradually increased with the increase of hypoxia.The difference was statistically significant(P<0.05).Conclusion:(1)Intermittent hypoxia can cause kidney tissue damage through inflammatory pathways.(2)Intermittent hypoxia can cause renal inflammatory response.The inflammatory pathways involved in TLR4 receptors may be one of the mechanisms that cause kidney inflammation.(3)Compared with no or mild hypoxia,moderate to severe hypoxia has more severe kidney damage.The degree of kidney damage is positively correlated with the severity of intermittent hypoxia.