| Objective:This study will indirectly understand the characteristics of glucose metabolism in the body during altitude acclimation by observing the characteristics of liver glucose metabolism in rats under different altitudes and different acclimation time,so as to lay a theoretical foundation for revealing the occurrence and basic mechanism of human acute altitude sickness.Methods:A total of 110 healthy male rats were divided into 400 m plain control group(group C)and 2260 m medium altitude exposure group(M1)for 1 day,3 days,7 days,M7,15 days,and 30 days.1 day group(H1),3 day group(H3),7 day group(H7),15 day group(H15)and 30 day group(H30)exposed to 4300 m high altitude had 10 birds in each group.All groups were raised in the animal laboratory at the corresponding altitude,and the samples were taken.The contents of glucose,alanine aminotransferase(ALT),blood lactic acid,liver lactic acid,liver ATP and liver glycogen in plasma were determined,as well as Isocitrate dehydrogenase(Isocitrate dehydrogenase),a key enzyme in the tricarboxylic acid cycle of glucose metabolism in liver tissue ICDH,glucose-6-phosphatase G6 Pase and am P-activated protein kinase AMPK m RNA and protein expression levels.Results:(一)Comparison of exposure time groups at the same altitude(1)Compared with plain control group,there were no significant differences in the contents of ALT,blood glucose,blood and liver lactic acid in medium and high altitude exposure groups compared with plain control group(P>0.05);(2)In the process of acclimation at different altitudes,the m RNA and protein expression levels of ICDH in rat liver tissue increased firstly and then decreased to the level of plain control group with the gradual extension of hypoxia time.Compared with plain control group,the expression level of ICDHm RNA in liver tissues of middle and high altitude groups was significantly increased at day 1,day 3 and day 7 of exposure(P<0.05),with the most significant increase in altitude group at day 3(P< 0.05),and the most significant increase in high altitude group at day 1(P< 0.05).theprotein expression level of ICDH and the content of ATP in liver tissue of rats in middle altitude group were significantly increased on day 3 of exposure(P<0.05).The expression level of ICDH protein and the content of ATP in liver tissue of rats in high altitude group increased significantly on the 1st,3rd and 7th day of exposure(P< 0.05),and the increase was most significant on the 1st day.(3)In the process of acclimation at different altitudes,the expression levels of G6 Pasem RNA and protein in rat liver tissue gradually increased first and then decreased to the level of plain control group with the gradual extension of hypoxia time.Compared with plain control,the levels of exposure in middle and high altitude groups were significantly higher on day 1,3 and 7(P<0.05),and the most significant increases were observed on day 3.the expression level of G6 Pase protein in liver tissue of rats in middle altitude group was significantly increased on day 3 and 7(P<0.05),and the most significant increase was on day 3;The expression level of G6 Pase protein in liver tissue of rats in high altitude group was significantly increased on day 1,3 and 7(P<0.05),and the most significant increase was on day 3.liver glycogen concentration of rats in medium and high altitude groups increased significantly on the 1st,3rd and 7th days of exposure(P<0.05),with the most significant increase on the 3rd day in medium altitude group and the most significant increase on the 7th day in high altitude group.(4)During acclimation at different altitudes,the m RNA and protein expression levels of AMPK in liver tissues of rats showed a trend of gradual decrease along with the gradual increase of hypoxia time.Compared with plain control group,the expression level of AMPKm RNA and AMPK protein in middle and high altitude groups decreased significantly on day 1,3,7,15 and 30 of exposure,and the expression level of AMPKm RNA and AMPK protein in middle altitude group decreased most significantly on day 7 and day 15 of exposure(P<0.05).The m RNA and protein levels of AMPK in high altitude group decreased most significantly on day 15(P<0.05).(5)Compared with plain control group,the m RNA expression level of HIF-1α in liver tissue of rats was significantly increased at day 1,3,7 and 15(P< 0.05)with the gradual prolongation of hypoxia time during acclimation at different altitudes.The expression level of HIF-1α protein was significantly increased on the first and third day of exposure(P<0.05),and the most significant increase was found on the third day.(二)Comparison of different altitude groups at the same time(1)At different altitudes and at the same exposure time,there were no significant differences in the contents of ALT,blood glucose,blood lactic acid and liver lactic acid among all groups(P>0.05).(2)At the same exposure time at different altitudes,there was no significant difference in the expression level of ICDHm RNA in liver tissues of rats in the high altitude group at day 1,3,7,15 and 30 compared with that in the middle altitude group(P>0.05).The expression level of ICDH protein and liver ATP concentration in high altitude group were higher than those in middle altitude group on day 1 and 7(P <0.05).(3)Under the same exposure time at different altitudes,the m RNA expression level of G6 Pase in liver tissues of rats in the high altitude group was significantly higher than that in the middle altitude group on day 1 and day 3(P< 0.05).On day 1,the protein expression level of G6 Pase in liver tissue of rats in high altitude group was significantly higher than that in middle altitude group(P<0.05).On the 1st,3rd and 7th day,liver glycogen concentration in high altitude group was significantly higher than that in middle altitude group(P<0.05).(4)Under the same exposure time at different altitudes,the m RNA and protein expression levels of AMPK in liver tissues of rats at the 1st,3rd,7th,15 th and 30 th days were statistically different among altitude groups(P<0.05).On day 15,the m RNA expression level of AMPK in liver tissue of rats in high altitude group was significantly lower than that in middle altitude group(P<0.05).At day 1,3,7,15 and 30,the AMPK protein in liver tissue of rats in high altitude group was significantly lower than that in middle altitude group(P<0.05).(5)At the same exposure time at different altitudes,the m RNA expression level of HIF-1α in liver tissue of rats in the high altitude group was not different from that in the middle altitude group at day 1,3,7 and 15(P>0.05).On day 1 and 3,theprotein expression level of HIF-1α in liver tissue of rats in high altitude group was significantly higher than that in middle altitude group(P<0.05).Conclusions: 1.There were no significant changes in ALT and blood glucose levels in rats at different altitudes and different time of taking,indicating normal liver function and stable blood glucose regulation in rats.2.In the process of acclimatization at different altitudes,with the prolongation of hypoxia time,glucose aerobic oxidative metabolism in rats at acute exposure stage may be significantly enhanced and a large amount of ATP may be released to provide energy for the body.Anaerobic oxidation is not significant,and the aerobic oxidation capacity is stronger at high altitude,and more ATP is released.3.In the process of acclimatization at different altitudes,the hepatic gluconeogenesis ability of acute exposure rats may be enhanced,and the hepatic glycogen reserve may be increased;Rats at high altitude had higher gluconeogenesis and higher liver glycogen reserve than rats at middle altitude.4.In the process of acclimation at different altitudes,AMPK is a transcription regulator in the process of glucose metabolism,and its decreased expression weakens the inhibitory effect on gluconeogenesis and enhances the gluconeogenesis process. |
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