| Objectives Through the establishment of intermittent hypoxia model to simulate breathing sleep suspended,gastric mucosa lesion caused by intermittent hypoxia and JNK pathway related factor to express the inner link,research of intermittent hypoxia on gastric mucosa damage of rats and its mechanism,and further investigate the intervention of melatonin,to provide theoretical basis for clinical prevention and treatment of OSA related gastric mucosa lesions.Methods Forty-eight adult clean male Wistar rats were stochasticly separated into 3 groups on the basis of their body weight: normal control group(NC group),intermittent hypoxia group(IH group)and melatonin group(MT group).The model was made continuously for 8 weeks.The MT group and IH group were put into the hypoxia box at 8:00 every day and were given intermittent hypoxia for 7 hours.At the same time,the NC group was put into the same plastic test box as the hypoxia box and given intermittent compressed air for 7 hours.Four rats in each group were randomly selected and killed at 2w,4w,6w and 8w,respectively.The pathological and general morphology of gastric tissue in rats were outsighted under naked eye and light microscope.The PH value of gastric juice was detected by PH probe,the levels of gastric tissue pepsin and oxidative stress indexes ROS,MDA and SOD were detected by ELISA.The protein expression levels of JNK,p-JNK,Bax and Bcl-2 in gastric mucosa were observed by immunized histochemical method,and the expression of JNK protein in rat gastric mucosa was detected by Western blot method.The levels of JNK mRNA,Bax mRNA and Bcl-2 mRNA in rat gastric mucosal cells were detected by Real-time PCR method.Results 1 Compared with the NC group,the pH of gastric juice in IH group and MT group decreased significantly,with the prolongation of time,while compared with IH group,the pH value of gastric juice of MT group decreased significantly(P<0.05).Compared with NC group,the level of gastric juice pepsin activity of IH group and MT group increased significantly with the prolongation of time,while compared with IH group,the level of gastric juice pepsin of MT group decreased significantly(P<0.05).2 There was no obvious injury of gastric mucosa in NC group under naked eye,but there were different degrees of bleeding,erosion and ulcer in IH group and MT group,and the injury was more serious with the prolongation of intermittent hypoxia.Compared with IH group,the injury of gastric mucosa in MT group was alleviated.Under light microscope,there were no pathological changes in gastric mucosa in NC group,but there were different degrees of inflammatory cell infiltration in the lamina propria of gastric mucosa in IH group and MT group,hemorrhage around gastric gland,destruction of gastric gland structure and unclear boundary,and the above changes were more obvious with the prolongation of hypoxia,and the histopathological changes of gastric mucosa in MT group were less than those in IH group.3 Compared with NC group,the contents of gastric mucosa ROS and MDA in IH group and MT group increased significantly,and the contents of ROS and MDA in MT group decreased significantly compared with IH group.Compared with NC group,the level of gastric mucosa SOD decreased in IH group and MT group,and decreased more significantly with the prolongation of intermittent hypoxia.Compared with IH group,the level of gastric mucosa SOD in MT group increased significantly(P<0.05).4 compared with NC group,the average optical density of JNK and p-JNK protein in gastric mucosa in IH group and MT group increased significantly,while compared with IH group,JNK and p-JNK albumen expressed of the gastric mucosa MT group declined sharply compared with IH group(P<0.05).Compared with NC group,the average optical density of Bax protein in gastric mucosa of IH group and MT group increased significantly,and the expression of Bcl-2 protein decreased significantly with the prolongation of time(P<0.05).Bax expression in the gastric mucosa of MT group that decreased significantly Compared to IH group and the expression of Bcl-2 protein increased significantly(P<0.05).5 Compared with NC group,the expression of JNK mRNA in gastric mucosa of IH group and MT group increased significantly with the prolongation of intermittent hypoxia,while the expression of JNK mRNA in MT group decreased significantly compared with IH group(P<0.05).Compared with NC group,the expression of Bax mRNA and Bcl-2 mRNA in gastric mucosa of IH group and MT group increased significantly,and the change was more obvious with the prolongation of the time(P<0.05).Compared with IH group,the expression of Bax mRNA and Bcl-2 mRNA in gastric mucosa of MT group decreased significantly(P<0.05).Conclusions 1 Intermittent hypoxia can cause imbalance of gastric mucosal oxidative stress(increased ROS and MDA content)and antioxidant stress(decreased SOD level)system,gastric mucosal secretion dysfunction(decreased PH value and increased pepsin level),activation of gastric mucosal JNK pathway(increased JNK,p-JNK,Bax expression,decreased Bcl-2 expression),and gastric mucosal injury.2 Melatonin can inhibit the oxidative stress in gastric mucosa of intermittent hypoxia rats(ROS,MDA level decreased,SOD level increased),improve the secretion function of gastric mucosa(PH value increased,pepsin level decreased),inhibit the JNK pathway of gastric mucosa(JNK,p-JNK,Bax expression decreased,Bcl-2 expression increased),and reduce the injury of gastric mucosa.Figure 18;Table 13;Reference 117... |
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