The Study On The Mechanisms Of Inflammation And Oxidative Stress Damage In The Rats Pancreas Tissue Caused By Intermittent Hypoxia Of Sleep Apnea Model

Objective:In order to explore the association between the inflammation and oxi dative stress mechanism of rats pancreatic tissue damage,we established a sleep apnea model of OSAHS that involved exposing rats to different oxygen concen trations of IH to observe the levels of inflammation markers IL-6, IL-1β, TNF-a and oxidative stress transcription factors ERK, JNK, p38MAPK in pancreatic tissue.Methods:1. To establish animal model of different concentrations of intermittent hypoxia in rats,Thirty adult male Wistar rats of 200-220g were divided into 5 groups,6 rats in each group, blank control group (under normoxia natural exposure, NC),5% oxygen concentration group,7.5% oxygen concentration group,10% oxygen concentration group,12.5% oxygen concentration group (IH-1, IH-2, IH-3, IH-4), every day hypoxia exposure time for 9Am-5Pm and exposed for 12 weeks. After rats were exposed to 13 weeks,acquire bronchoalveolar lavage fluid and pancreatics tissue.2. After rats were exposed to 12 weeks:(1) ELISA assay was performed to detecte the levels of inflammatory cytokines IL-6, IL-1β, TNF-α in pancreatics tissue.(2) Western blot assay was performed to detecte the protein levels of transcription factor ERK, JNK, p38MAPK in pancreatics tissue.Results:1.Markers of inflammation within intermittent hypoxia rat pancreatic tissue:(1) Compared with NC group, The levels of IL-6 was significantly increased in the all oxygen concentrations IH group, Comparisons among groups had Significant difference (F=25.6,P=0.000).IH-1 and IH-2 group compared with NC group difference was statistically significant (P< 0.01), in addition to IH-3 with IH-4 group, the differences among other groups with statistical significance (P< 0.05).(2) Compared with NC group, The levels of TNF-a was significantly increased in the all oxygen concentrations IH group, Comparisons among groups had Significant difference (F=81.32, P=0.000).IH-1 and IH-2 group compared with NC group difference was statistically significant (P< 0.01), in addition to IH-3 with IH-4 group and IH-2 with IH-3 group, the differences among other groups with statistical significance (P< 0.05).(3)Compared with NC group, The levels of IL-1β was significantly increased in the all oxygen concentrations IH group, Comparisons among groups had Significant difference (F=23.85, P=0.000).IH-l and IH-2 group compared with NC group difference was statistically significant (P< 0.01), in addition to IH-3 with IH-4 group and IH-1 with IH-2 group, the differences among other groups with statistical significance (P< 0.05).2.Markers of oxidative stress within different oxygen concentrations rats of intermittent hypoxia:(1) Compared with NC group, the protein levels of p-ERK in pancreatic tissue was significantly increased in the all oxygen concentrations IH group,Comparisons among groups had Significant difference(F=44.75, P= 0.000). in addition to IH-4 with NC group and IH-2 and IH-3 group, the differences among other groups with statistical significance (P< 0.01).(2)Compared with NC group, the protein levels of p-JNK in pancreatic tissue was significantly increased in the all oxygen concentrations IH group,Comparisons among groups had Significant difference(F=309.73, P= 0.000). The comparison of IH group and NC were statistically significant, and the difference between the different groups was statistically significant (P< 0.01).(3)Compared with NC group, the protein levels of p-p38MAPK in pancreatic tissue was significantly increased in the all oxygen concentrations IH group,Comparisons among groups had Significant difference(F=188.96, P= 0.000). The comparison of IH group and NC were statistically significant, and the difference between the different groups was statistically significant (P< 0.01).Conclusion:1.IH can lead to pancreas tissue inflammatory injury by imbalance of inflammatory and anti-inflammatory system.2.Inflammatory injury induced by IH is partially dependent on the oxygen concentrations of IH.3.IH can lead to the activation of different transcription factors which causes oxidative stress in pancreatic tissue,including ERK,JNK and p38MAPK.The protein levels of ERK,JNK and p38MAPK in pancreatic tissue was significantly increased.