| Objective: A large number of studies have shown that chronic intermittent hypobaric hypoxia(CIHH)has protective effects on various tissues of the body.Recently,studies have shown that CIHH can reduce endoplasmic reticulum stress(ERS)-mediated liver injury in metabolic syndrome(MS)rats,and improve insulin resistance,glycolipid metabolism disorders and fatty degeneration of liver tissue.There is a functional coupling between autophagy and ERS.It is not yet clear whether CIHH can inhibit ERS and exert hepatoprotective effect by regulating autophagy in MS rats.In this study,we observed the effects of CIHH on endoplasmic reticulum stress-related proteins GRP78,CHOP,autophagy-related proteins Beclin-1,LC3-II/I,p62,and autophagy-regulated signaling pathway proteins AMPK and m TOR in the liver tissue of MS rats,and revealed the possible mechanism of autophagy in the protective effect of CIHH on the MS rats liver tissue.Methods: Adult male Sprague-Dawlay rats were randomly divided into four groups: control group(CON),chronic intermittent hypobaric hypoxia treatment group(CIHH),metabolic syndrome model group(MS),metabolic syndrome model + chronic intermittent hypobaric hypoxia treatment group(MS + CIHH).CON rats and CIHH rats were fed with conventional diet and ordinary drinking water.MS rats and MS + CIHH rats were fed with high fat diet and 10% fructose water to induce MS.Sixteen weeks later,CIHH and MS+ CIHH rats were exposed to hypobaric hypoxia at altitude of 5000 meters,6hours per day for 28 days,and the rest of the time were exposed to normal oxygen.CON and MS rats were always exposed to normoxia.During CIHH treatment,animal weight and systolic arterial pressure(SAP)were measured in the same time every week.After CIHH treatment,body length,body weightand fat were measured to get Lee’s index and fat coefficient;fasting blood glucose and lipid were measured by venous blood;liver histomorphological changes were observed by HE staining;endoplasmic reticulum stress-related proteins GRP78 and CHOP,autophagy-related proteins Beclin-1,LC3-II/I,p62 and autophagy regulatory signaling pathway proteins p-AMPK and p-m TOR were detected by Western blot.Graphpad Prism 5.0 system was used for data analysis and processing.Results:1.Compared with CON rats,the body weight,Lee’s index,fat coefficient,and arterial systolic pressure were increased significantly in MS rats(P<0.05);CIHH treatment could improve obesity and elevating arterial systolic pressure in MS rats(P<0.05),but had no effect on body weight and arterial systolic pressure in CON rats(P>0.05).2.Compared with CON rats,the fasting blood glucose,cholesterol,triglyceride and low density lipoprotein cholesterol(LDL)were increased significantly(P<0.05),and high density lipoprotein cholesterol(HDL)was significantly decreased in MS rats(P<0.05).The above biochemical indexes of CIHH rats were no difference from CON rats(P>0.05).However,the abnormal biochemical indexes in MS + CIHH rats were significantly improved,compared with MS rats(P<0.05).CIHH treatment could improve the hyperglycemia and hyperlipidemia in MS rats.3.Compared with CON rats,HE staining showed the obvious steatosis and some strip-like changes in hepatocytes of MS rats.The morphological changes of MS + CIHH rats were significantly improved,compared with MS rats.4.Compared with CON rats,the protein expression of GRP78 and CHOP was increased significantly in liver tissue of MS rats(P<0.05),and was no significant difference in liver tissue of CIHH rats(P>0.05),but CIHH could effectively antagonize the up-regulation of protein expression in MS rats(P<0.05).5.Compared with CON rats,the expressions of autophagy-relatedproteins Beclin-1,LC3-II/I and p62 were significantly increased in liver tissue of MS rats(P<0.05),while was no significant difference in CIHH rats(P>0.05).Compared with MS rats,the expression of these three proteins was significantly decreased in liver tissue of MS + CIHH rats(P<0.05).6.Compared with CON rats,the phosphorylation levels of AMPK were significantly lower(P<0.05),while the phosphorylation levels of m TOR were significantly increased in liver tissue of MS rats(P<0.05).Compared with MS rats,the phosphorylation levels of AMPK were increased significantly in liver tissue of MS + CIHH rats(P<0.05),while the phosphorylation levels of m TOR were decreased significantly(P<0.05).Conclusion:In the MS rats induced by high-fat-high-fructose diet,the liver tissue was impaired.CIHH treatment significantly improved the damage of MS rats liver through activating AMPK-m TOR signaling pathway,regulating the autophagy function,thereby inhibiting endoplasmic reticulum stress in liver. |
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