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Effects Of Chronic Intermittent Hypoxia Through NF-kappa B Pathway On Pancreatic Inflammation And Glucose Metabolism In Rats

Posted on:2021-04-13Degree:MasterType:Thesis
Country:ChinaCandidate:L D ZhuFull Text:PDF
GTID:2404330626460149Subject:Internal Medicine
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Objective: Chronic intermittent hypoxia(CIH)SD rat model was constructed by intermittent hypoxia chamber,and the effects of CIH on the levels of inflammatory factors TNF-?,IL-6 and CRP in serum and pancreatic tissues of SD rats,as well as the levels of fasting blood glucose,fasting insulin,glycated hemoglobin and homeostasis model assessment insulin resistance index(HOMA-IR)were observed.The effect of index was compared with the changes of above indexes after using the nuclear factor of kappa B(NFkappa B)pathway blocker pyrrolidine dithiocarbamate(PDTC).To analyze the relationship between HOMA-IR and serum inflammatory factors in SD rats of CIH group.To investigate the mechanism of the effect of intermittent hypoxia mode in obstructive sleep apnea hypopnea syndrome(OSAHS)on pancreatic inflammation and glucose metabolism in SD rats.Methods: Eighteen healthy male SD rats were selected and divided into three groups according to random number table method,namely,A was normal control group(NC group),B was chronic intermittent hypoxia group(CIH group),C was drug group(CIH + PDTC group).Group B and C were given nitrogen and oxygen for 8 hours every day.Group A was fed in normal oxygen.Intermittent hypoxic SD rat model was established after 6 weeks.SD rats in each group were anesthetized on the first day of the seventh week,and SD rats were killed by Bloodletting through abdominal aorta,and pancreatic tissues and serum were reserved for use.The pathological changes of HE staining in pancreatic tissues of each group were compared.The levels of TNF-?,IL-6,CRP,fasting blood glucose,fasting insulin and glycated hemoglobin in serum and pancreas groups were measured by ELISA.HOMA-IR was calculated by steady state model method,and insulin resistance was evaluated by HOMA-IR.The expression of NF-kappa Bp65 in pancreatic tissues of each group was detected by immunohistochemistry.Pearson correlation analysis was used to analyze the relationship between HOMA-IR and serum inflammatory factors in SD rats of CIH group.Results: 1.After 6 weeks of exposure to intermittent hypoxic environment,hematoxylin and eosin(HE)staining suggested that the damage of pancreatic tissue was more obvious in SD rats in CIH group,and less in CIH + PDTC group than in CIH group.2.After exposure to intermittent hypoxia for 6 weeks,the expression levels of serum TNF-?,IL-6 and CRP in CIH group and CIH+PDTC group increased with statistical significance compared with NC group(p<0.05);compared with CIH group,the expression levels of serum TNF-?,IL-6 and CRP in CIH+PDTC group decreased with statistical significance(p<0.05).3.After exposure to hypoxic environment for 6 weeks,compared with NC group,the expression levels of TNF-?,IL-6 and CRP in pancreatic tissues of SD rats in CIH group and CIH+PDTC group were increased,with significant difference(p<0.05);compared with CIH group,the expression levels of TNF-?,IL-6 and CRP in pancreatic tissues of CIH+PDTC group were decreased,with significant difference(p<0.05).4.After exposure to hypoxic environment for 6 weeks,the levels of fasting blood glucose,fasting insulin and glycated hemoglobin in SD rats were not significantly different among the groups(p>0.05);compared with NC group,HOMA-IR in CIH group was increased,the difference was statistically significant(p<0.05);compared with CIH group,HOMA-IR in CIH + PDTC group was decreased,the difference was statistically significant(p<0.05).5.After exposure to hypoxic environment for 6 weeks,compared with NC group,the expression level of NF-kappa Bp65 in pancreatic tissue of CIH group and CIH+PDTC group increased,with a statistically significant difference(p<0.05);compared with CIH group,the expression level of NF-kappa Bp65 in pancreatic tissue of CIH+PDTC group decreased,with a statistically significant difference(p<0.05).6.After exposure to hypoxic environment for 6 weeks,Pearson correlation analysis showed that HOMA-IR of SD rats in CIH group was positively correlated with the expression levels of serum TNF-?,IL-6 and CRP in the same group,and the difference was statistically significant(r=0.844,r=0.832,r=0.829;p<0.05).Conclusions: 1.Chronic intermittent hypoxia can lead to inflammation in serum and pancreatic tissue,which may be mediated by the NF-kappa B pathway.2.Chronic intermittent hypoxia may cause insulin resistance through the NF-kappa B pathway.3.Inhibiting the NF-kappa B pathway can alleviate the inflammatory response of pancreatic tissue and improve insulin resistance.
Keywords/Search Tags:Chronic intermittent hypoxia, obstructive sleep apnea hypopnea syndrome, inflammation, insulin resistance
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