| OBJECTIVE: By analyzing the expression difference of AMPK-SKP2-CARM1 signaling pathway in pancreas of SD rats with different doses of arsenic,the association between arsenic and diabetes was clarified.METHODS: Fifty Specific SPF(Pathogen Free)SD rats were randomly divided into control group,diabetic model group,sodium arsenite(low-dose,medium-dose,high-dose)group and arsenic group exposed orally for 16 weeks with 10 males and 10 females in each group.According to the Median Lethal Dose(LD50,median Lethal dose)of SD rats(1/100,1/20,1/4),arsenic poisoning components in low-dose group,medium-dose group and high-dose group were divided.Chain of diabetic model group rats by intraperitoneal injection of urea with cephalosporins(STZ Streptozotocin)to establish the model of blank control group for comparison,normal eating,drinking distilled water;Urine sugar test paper was used to determine the classification of urine sugar by visual qualitative colorimetry.Blood glucose test paper was used to measure blood glucose after caudal vein collection.Real-time fluorescence quantitative technique was used to observe the m RNA expression levels of rat pancreas with different doses of sodium arsenite.Western blot was used to observe the protein expression of pancreatic tissue at different doses of sodium arsenite.Results: 1.General signs: Compared with the control group,the arsenic exposure group showed signs such as slow movement,lethargy,lethargy,rough and lustrous hair,etc.In the diabetic model group,urine volume,food intake and water intake were significantly increased,and body weight was decreased,and symptoms such as lethargy,lethargy,lethargy,reduced activity,and unsteadiness were observed.2.Organ coefficients: The organ coefficients of liver,kidney and pancreas of SD rats in high-dose group and diabetic model group were higher than those in control group(P < 0.05).3.Blood glucose: at week 14 and 16,the blood glucose of the arsenic high-dose group was higher than that of the control group(P < 0.05),that of the diabetes model group was higher than that of the control group(P < 0.05),that of the diabetes model group was higher than that of the arsenic group(P < 0.05);4.Urine sugar: At the 16 th week of the experiment,the urine sugar test results of 2 SD rats in the high-dose arsenic group were "+" and 1 was "±",and the urine sugar test results of 7 rats in the medium-dose group were "±",and the urine sugar test results of the high-dose arsenic group were increased(P < 0.05).5.Histopathological results: Compared with the control group,the number and volume of islets in pancreatic tissue of rats in diabetic group were decreased,some of the beta cells were vacuolated,lymphocyte infiltrated,and a few of the capillary walls of the islets were hyalinized.In the high-dose group,the number of islets decreased significantly,the structure of some glandular lobule was damaged,inflammatory cells infiltrated in the interstitium,and interlobule ducts were dilated.6.m RNA expression results: Compared with the control group,the mRNA expressions of ampkα1 and skp2 genes in arsenic exposed groups and diabetes model groups gradually decreased with the increase of dose(P < 0.05).Compared with the control group,the mRNA expression levels of p62 and lc-3 genes in arsenic infected groups and diabetes model groups gradually increased with the increase of arsenic dose(P< 0.05).7.Protein expression results: As the dose increased,the protein expression levels of AMPKα1 and SKP2 genes in the pancreatic tissue of SD rats in the arsenic group were decreased compared with that in the control group(P < 0.05),while the protein expression levels of P62 and LC3-Ⅱ/Ⅰ genes were increased in the arsenic group(P < 0.05).The protein expression of LC3-Ⅱ/Ⅰ in diabetic model group showed a decreasing trend(P <0.05).Conclusion: Long-term exposure to arsenic in drinking water can cause different degrees of toxic damage to SD rats.Chronic arsenic exposure may lead to changes in the level of autophagy in pancreatic tissue of SD rats by regulating AMPK-SKP2-CARM1 signaling pathway,which may be one of the mechanisms of arsenic induced pancreatic tissue injury. |
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