| Objective:To investigate the regulatory effect of GLP-1 on the PERK-e IF2α-ATF4 pathway in non-alcoholic fatty pancreas disease.Methods:Five-week-old male C57BL/6J mice of SPF grade were randomly divided into two groups: high fat diet group and normal chow group.After 16 weeks of feeding,one mouse was randomly selected to die and then determine whether the model of non-alcoholic fatty pancreas disease was success.The normal diet group was classified into the normal group(A,n =10),then the high-fat diet group was further randomly divided into the control group(B,n =10)and the experimental group.The normal group was given normal chow and intraperitoneal injection of normal saline(0.6mg/kg.d),the model group was given high-fat feed and intraperitoneal injection of normal saline(0.6mg/kg.d),and the experimental group was given high-fat feed and intraperitoneal injection of Liraglutide(0.6mg/kg.d).During the intervention,drinking water was free,the duration of intervention was 4 weeks,and the specimens were collected 12 hours after fasting.Pancreas tissue was collected after 4 weeks of intervention and 12 hours of fasting.one part of tissue for pathological sections,other tissue saved in-80 C refrigerator to measure protein expression levels.Results:1.Body weight: compared with normal group,bodyweight of the model group significantly increased,and the difference was statistically significant(36.10±2.72vs29.10±2.37,P =0.000);compared with the model group,bodyweight of the experimental group significantly decreased,and the difference was statistically significant(28.50±1.58vs36.10±2.72,P =0.000);2.Pancrea Western blot :compared with normal group,the expression level of GRP78、PERK、e IF2α、ATF4、Caspase12 and CHOP in the control group significantly increased,and the difference was statistically significant[(GRP78)1.89±1.44vs0.47±0.35,P=0.013;(PERK)0.61±0.26vs0.14±0.42,P=0.000;(e IF2α)1.62±1.41vs0.20±0.12,P = 0.011;(ATF4)1.82±1.42vs0.39±0.23,P = 0.011;(Caspase12)2.42±1.11vs0.99±0.53,P=0.002;(CHOP)1.91±1.49vs0.68±0.46,P=0.031];compared with control group,the expression level of GRP78、PERK、e IF2α、ATF4、Caspase12 and CHOP in the experimental group significantly decreased,and the difference was statistically significant[(GRP78)0.60±0.35vs1.89±1.44,P=0.021;(PERK)0.21±0.13vs0.61±0.26,P=0.000;(e IF2α)0.40±0.19vs1.62±1.41,P=0.023;(ATF4)0.52±0.19vs1.82±1.42,P=0.019;(Caspase12)0.96±0.46vs2.42±1.11,P=0.002;(CHOP)0.40±0.24vs1.91±1.49,P=0.011];3.Immunohistochemistry: compared with normal group,the integrated option density of GRP78、PERK、e IF2α、ATF4、Caspase12 and CHOP in the control group significantly increased,and the difference was statistically significant[(GRP78)6821.27±1389.20vs2167.85±1211.00,P = 0.000;(PERK)4131.04±1840.32vs1073.45±264.99,P = 0.000;(e IF2α)5360.33±1302.93vs1310.78±411.63,P = 0.000;(ATF4)4733.27±2560.21vs2722.43±684.32,P = 0.035;(Caspase12)6393.62±1183.75vs2934.61±965.82 P = 0.000;(CHOP)6214.80±1654.93vs2183.27±523.76,P=0.000];compared with model group,integrated option density of GRP78 、 PERK 、 e IF2α 、 ATF4 、 Caspase12 and CHOP in the experimental group significantly decreased,and the difference was statistically significant[(GRP78)1995.54±579.60vs6821.27±1389.20,P = 0.000;(PERK)1351.66±443.85vs4131.04±1840.32,P = 0.001;(e IF2α)2117.07±502.56vs5360.33±1302.93,P = 0.000;(ATF4)1047.44±407.41vs4733.27±2560.21,P = 0.002;(Caspase12)2041.62±621.56vs6393.62±1183.75,P = 0.000;(CHOP)1528.48±431.76vs6214.80±1654.93,P=0.000]。Conclusions:1.GLP-1 regulatory PERK-e IF2α-ATF4 pathways improve the ERS of nonalcoholic fatty pancreatic disease in mice2.GLP-1 regulates apoptosis of pancreatic cells mediated by CHOP、Caspase12 pathways... |
