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Experimental Study On Rat Model Of Intermittent Hypoxia:Study1:the Investigation Of The Oxidati-ve Stress,Inflammation Reaction.Study2:Related Effects On The Thyroid Gland

Posted on:2015-02-23Degree:MasterType:Thesis
Country:ChinaCandidate:P XuFull Text:PDF
GTID:2254330431451946Subject:Internal medicine
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Objective In order to mimic the intermittent hypoxia during sleep of obstructive sleep apnea hypopnea syndrome(OSAHS)in humans,we established imtermittent hypoxia(IH) animal model in rats, to investigate the oxidative stress,inflammation reaction in rats of intermittent hypoxia.Methods Healthy Sprague-Dawley(SD) rats (16) were randomly divided into2groups:the control group and the IH group. The rats in IH group were placed in ananimal chamber subjected to imtermittent hypoxia. Circulation to the cabin filled with nitrogen, oxygen and compressed air cycle of120s, pure nitrogen input for30seconds (the oxygen concentration gradually dropped to6-7%),resting10seconds (oxygen concentration was maintained for6-7%), pure oxygen input20seconds (oxygen concentration gradually rose to20-21%),input the compressed air60seconds (oxygen concentration fluctuations in20.8±0.3%). Experimental design for about8hours (9am-17pm) every day,7days a week, for four weeks, a total of28days..The rats incontrolgroup were Placed in the same animal chamber at the same time every day at the rearing chamber of the same specification, and accessed to the same flow of air..After the experiment,we measured the level of MDA,SOD,GSH-PX with biochemical method,and the level of IL-6,TNF-a by radioimmunoassay in rats serum.Results1. The levels of MDA in rats serum:the control group was5.09±0.51nmol/ml, IH group was5.74±0.38nmol/ml. Compared with the control group, the levels of MDA was increased in IH group,and had a significant difference (P=0.011<0.05).2. The levels of SOD in rats serum:the control group was67.21±6.68U/ml, IH group was56.70±6.34U/ml. Compared with the control group.the levels of SOD was discreased in IH group,and had a significant difference (P=0.006<0.05).3. The levels of GSH-PX in rats serum:the control group was811.5±14.9U/ml, IH group was779.16±30.27U/ml.Compared with the control group, the levels of GSH-PX was discreased in IH group,and had a significant differenc (P=0.017<0.05).4. The levels of IL-6in rats serum:the control group was166.04±30.92pg/ml, CIH group was211.01 ±33.24pg/ml.Compared with the control group, the levels of IL-6was increased in IH group,and had a significant difference (P=0.014<0.05).5. The levels of TNF-a in rats serum:the control group was59.11±10.07pg/ml, IH group74.22±7.68pg/ml. Compared with the control group, the levels of TNF-a was increased in IH group,and had a significant difference (P=0.005<0.05).Conclusion1. The intermittent hypoxic conditions can lead to the levels of MDA increased, while the levels of SOD and GSH decreased in rats serum, there are oxidative stress in rats of intermittent hypoxic and,the anti-oxidative capacity can be decreased in intermittent hypoxic conditions;2. The intermittent hypoxic conditions can lead to the levels of IL-6and TNF-a increased in rats serum.This suggests that there are inflammation reaction in rats of intermittent hypoxic. Objective In order to mimic the intermittent hypoxia during sleep of obstructive sleep apnea hypopnea syndrome(OSAHS)in humans,we established imtermittent hypoxia(IH) animal model in rats, to investigate the thyroid hormone, thyroid ultrastructure and the expression of thyroid Peroxiredoxin5in rats of intermittent hypoxia.Methods Healthy Sprague-Dawley(SD) rats (16) were randomly divided into2groups:the control group and the IH group The rats in IH group were placed in ananimal chamber subjected to imtermittent hypoxia. Circulation to the cabin filled with nitrogen, oxygen and compressed air cycle of120s, pure nitrogen input for30seconds (the oxygen concentration gradually dropped to6-7%),resting10seconds (oxygen concentration was maintained for6-7%), pure oxygen input20seconds (oxygen concentration gradually rose to20-21%),input the compressed air60seconds (oxygen concentration fluctuations in20.8±0.3%). Experimental design for about8hours (9am-17pm) every day,7days a week, for four weeks, a total of28days..The rats incontrolgroup were Placed in the same animal chamber at the same time every day at the rearing chamber of the same specification, and accessed to the same flow of air..After the experiment,we measured the level of FT3,FT4,TSH by radioimmunoassay in rats serum,and observed the changes of rat thyroid ultrastructure under electron microscope,and measured Peroxiredoxin5expression in rat thyroid by immunohistochemistry.Results1. The levels of FT3in rats serum:the control group was0.40±0.17ng/dl, IH group was0.46±0.19ng/dl. Compared with the control group, the levels of FT3was increased in IH group,but did not have a significant difference (P=0.521<0.05).2. The levels of FT4in rats serum: the control group was4.20±0.92ng/dl, IH group was2.98±0.64ng/dl. Compared with the control group,the levels of FT4was increased in IH group,and had a significant difference (P=0.009<0.05).3. The levels of TSH in rats serum:the control group was12.34±1.89uIU/ml, IH group was9.36±1.17uIU/ml.Compared with the control group, the levels of TSH was increased in IH group,and had a significant differenc (P=0.003<0.05).4. Ultrastructure of rat thyroid in IH group: Change of hypoxia overall.5. Peroxiredoxin5expression in rat thyroid:Thyroid PRDX5positive staining cells mainly located in the cytoplasm of the thyroid, the average optical density of the control group was0.22±0.01, the average optical density of IH group0.30±0.01the control group was59.11±10.07pg/ml, IH group72.58±5.78pg/ml. Compared with the control group, PRDX5expression in rat thyroid was higher in IH group,and had a significant difference.(P=0.002<0.05).Conclusion1. The intermittent hypoxic conditions can lead to the levels of FT4,TSH decreased.This suggestes that intermittent hypoxia can cause rats’hypothalamus-pituitary thyroid axis and thyroid function decline or abnormal itself, leading to changes in thyroid hormone levels;2. The intermittent hypoxic conditions can lead to rats’ thyroid ultrastructural hypoxia changes;3. The intermittent hypoxic conditions can lead to the expression of rat thyroid PRDX5increased. This suggests that intermittent hypoxia can lead the anti-oxidative capacity of rat thyroid increased, also indirectly suggests that there are oxidative stress in rat thyroid of intermittent hypoxic.
Keywords/Search Tags:obstructive sleep apnea hypopnea syndrome, intermittent hypoxia, oxidative stress, inflammation, malondialdehyde, superoxide dismutase, glutathioneperoxidase, interleukin-6, tumor necrosis factor-αobstructive sleep apnea hypopnea syndrome
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