| Objective: To set up the animal model of New-Zealand rabbit with obstructive sleep apnea-hypopnea Syndrome (OSAHS), and to observe endothelin-1 (ET-1) and angiotensin II (AngII) in blood plasma and the expression of vascular endothelial growth factor (VEGF) in renal cortex under OSAHS and treated by mandible advanced device (MAD). So that to provide the theoretical base and laboratory data for treatment of cognition disorders caused by OSAHS in clinical patients.Methods: Thirty male New Zealand rabbits were randomly divided into three groups: group OSAHS, group MAD and control group and 10 rabbits in each. A total of 2ml polyacrylamide hydrogel were injected into rabbit soft palate of group OSAHS and group MAD. Obvious snore and intermittent apnea were observed. After injection, cephalometrical data of the upper airway width at upper 1/4 point, middle point and 3/4 point in dorsal position were significantly decreased compared with control group. The data of saturation of blood oxygen after injection decreased by 22% than that of control group. Animal model of OSAHS was set up successfully. Group MAD animals were worn mandible advanced device (MAD). So that there were group OSAHS, group MAD and control group.The cephalometry of upper airway of three groups by dorsal position was made and measured. One milliliter auricle arterial blood was collected and blood gas analysis was performed before and after animal model set-up when apnea appeared in the animals of group OSAHS.After animal model set-up, 10% Chloral Hydrate was perfused by mouth of the animals in three groups by 5-6ml/kg, and slept 4-6 hours by dorsal position was performed every day for 8 weeks.After sleep for 8 weeks by dorsal position, the animals of three groups were anaesthetized the with 1% pentobarbital sodium and followed 4ml of blood from external jugular vein were obtained, the blood samples were put in 5ml tube with 30μl 7.5%EDTA . The blood samples were centrifuged at 4?C for 15 min, 3000roll/min, and subpackaged blood plasma into 1.5ml centrifuge tube and then conserved at -80?C. Both ET-1and AngII were Detected by the method Enzyme-linked Immunosorbent Assay (ELISA).Under the same anesthetic situation of animals, left kidney was obtained and put into 10% formalin followed by paraffin imbedding and immunohistochemistry staining, then sections were observed under AX-80 universal microscope. The sections were analyzed using Miprd image analytical system. Ten visual field were chosen in a section randomly and analyzed by auto-analyzer procedure. The mean value of Integral optical density was obtained. At the same time, the tissue of injection site was obtained, and fixed in 10% formalin and observed histologically.The statistical analyses of the airway width analysis, blood gas analysis, blood samples and image analysis were performed using the SPSS13.0 statistical program. (P<0.05)Results:1 General state of animals: When animals slept in dorsal position, animals of control group didn't have snore and apnea, whose anapnea were stable. Animals of group OSAHS had obvious snore and intermittent apnea. Animals of group MAD had stable anapnea or light snore, and none had apnea.2 Cephalometrical data of the upper airway space at upper 1/4 point, middle point and 3/4 point of group OSAHS were significantly decreased compared with that both group MAD and control group respectively after animal model set-up (P<0.05).The result of blood gas analysis showed that after animal model set-up, the data of saturation of blood oxygen and partial pressure of oxygen of group OSAHS were more decreased significantly than those of both group MAD and control group (P<0.05). The data of partial pressure of carbon dioxide of both group OSAHS and group MAD were more increased significantly than those of the control group (P<0.05).3 Histological observation of the tissue from the injection site: Hyalo-white jelly which was invested integrally in the soft plate could be seen by naked eye, and the jelly was tenacious and flexible. Under light microscope, there was integrated integument around polyacrylamide hydrogel, which was comprised with collagen fibers and elastic fibers. polyacrylamide hydrogel was dyed with blue,and no tissue damage and necrosis were observed.4 The data of blood plasma: Compared with group MAD and control group, The level of ET-1 and AngΙΙin group OSAHS increased significantly (P<0.05), Compared with control group, the level of ET-1 and AngΙΙin group MAD increased (P>0.05).5 The expression of VEGF protein in renal cortex: There were expression of VEGF protein in renal glomerulus, renal interstitium, renal small artery and epithelium of renal tubule. Compared with group MAD and control group, the expression of VEGF protein in group OSAHS increased significantly (P<0.05), Compared with control group, the expression of VEGF protein in group MAD increased (P>0.05).Conclusions:MAD treated OSAHS, which can decrease the level of ET-1 and AngΙΙin blood plasma and the expression of VEGF in renal cortex. |
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