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Effect Of Acute Hypoxia On Telomere Length Of Gastric Tissue In Rats And Its Mechanism

Posted on:2018-02-22Degree:MasterType:Thesis
Country:ChinaCandidate:Y TangFull Text:PDF
GTID:2334330536464103Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:The telomere length and Telomerase reverse transcriptase,Hypoxiainduci-ble factor 1α,Hypoxia-inducible factor 2α,reactive oxygen speciesexpression in the gastric tissue of rats under acute hypoxia were measured to observe the changes of telomere length in gastric tissue of rats under acute hypoxia.Specific mechanism.Methods:(1)40 male Wistar rats were randomly divided into control group(n = 10,Lanzhou,1500 m)and experimental group(n = 30,hypoxia chamber,5000 m).The experimental group was divided according to the time of hypoxia exposure The rats were sacrificed by HE staining and the morphological changes of gastric tissue were observed under microscope;(2)The DNA of gastric tissue of rats in each group was extracted and the telomere length was measured by Real-time PCR method;(3)The total RNA and protein in gastric tissue of rats in each group were extracted,and the levels of TERT,HIF-1 alpha and HIF-2 alpha m RNA and protein were measured by Real-time and Elisa;(4)The preparation of homogenates of gastric tissue of rats by chemical fluorescence method to measure the level of ROS;(5)The role of the rats’ gastric tissue TERT,HIF-1 and HIF-2 alpha and ROS levels in the change of telomere length in parallel,correlation analysis.Results:(1)In the simulated high altitude in a hypobaric chamber 5000m(severe hypoxia)construct plateau hypoxia on cell injury model of severe gastric tissue of rats,the pathological results showed that the hypoxia time prolonged,gastric mucosal injury gradually increased,mainly for gastric mucosa gland gradually atrophy,mucosal hyperemia,infiltration of inflammatory cells.Cell eosinophilic change;(2)Compared with the control group,the telomere length of the experimental group was prolonged at each time point(P <0.05),and the telomere length increased gradually with the prolongation of hypoxia time;(3)Between groups TERT,HIF-1 and m RNA alpha protein expression level and trend of telomere length is basically the same,but the HIF-2 alpha m RNA and protein expression of this trend was only increased in level,hypoxia for 7 days group;(4)The expression of ROS inexperimental group were compared with the control group increased(P < 0.05),and with the time of hypoxia,ROS expression increased gradually;(5)TERT and HIF-1 alpha 5 rats gastric tissue cells in protein expression levels were positively correlated(r=0.839 P < 0.05),and TERT and HIF-2 protein expression level had no correlation(r=0.298 p=0.062);(6)The gastric tissue of rats in TERT cells and HIF-1 m RNA expression levels were positively correlated(r=0.904 P < 0.05);TERT m RNA expression level is associated with telomere length was positive(r=0.962 P < 0.05),while TERT and HIF-2 alpha m RNA expression had no correlation(r=0.298 p=0.248).Conclusion:(1)Acute severe hypoxia can increase the expression of ROS in the body,leading to the injury of gastric cells;(2)Hypoxia can induce severe acute plateau gastric tissue of rats and extend the telomere,telomere length with the time of hypoxia and prolonged,and TERT was positively correlated with the expression of HIF-1 alpha,and HIF-2 expression had no significant correlation,which lead to serious consideration of acute high altitude hypoxia mechanism for telomere lengthening: elevated levels of cells HIF-1 expression in gastric tissue in rats,induced TERT expression and telomerase activity increased to extend telomeres;(3)Under the condition of acute severe hypoxia in high altitude,the rat gastric tissue cells can prolong the telomere to resist the damage of hypoxia,and it will not cause serious fatal injury.
Keywords/Search Tags:hypoxia, telomere, telomerase reverse, transcriptase hypoxia inducible factor, reactive oxygen species
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