The effects of hypertriglyceridemia on autophagy of acinar cells in acute necrotic pancreatitis rats / 中华胰腺病杂志

ABSTRACT

Objectives To observe the changes of autophagy of acinar cells in hypertriglyceridemia (HTG) associated acute necrotic pancreatitis(ANP) rats,and investigate the effects of HTG on autophagy and AP. Methods Forty SD rats were randomly divided into 4 groups using random number method, including control group,ANP group,hyperlipemia(HL) group,hyperlipidemia associated acute necrotizing pancreatitis (HANP) group. Control group and ANP group were fed with normal diet for 2 weeks,while the rats in HL and HANP group were fed with a high-fat diet for 2 weeks,and after the blood collection ANP and HANP rats were induced by 3.5% sodium taurocholate retrograde injection into the pancreaticobiliary duct to establish the ANP model. Rats in control group and HL group were intraperitoneally injected with equal volume of normal saline solution. ALL rats were sacrificed at 48 h after the model establishment. Serum triglyceride (TG), total cholesterol (TC) and serum amylase levels were measured; pancreatic tissue was histologically examined and scored; Transmission electron microscope were used to observe the intracellular ultrastructure changes and calculate the number of autophagosome and autophagic lysosome;the expressions of autophagy related proteins such as LC3,LC3Ⅱ, LC3Ⅰ, p62 and Lamp-2 were determined by Western-blot. Results After 2-week high fat diet, serum levels of TG and TC in HANP and HL groups were obviously higher than those in the control and ANP group;Serum amylase levels in HANP group and ANP group were higher than the control and HL group,and the differences were statistically significant (all P<0.05). Transmission electron microscope showed that the number of autophagosomes in ANP group was significantly higher than those in other three groups and the difference was statistically different(all P<0.05);and the autophagy activity in HANP group was impaired compared with ANP group. Compared with the control group, in ANP group the protein expressions of LC3 Ⅱ/Ⅰ ratio and p62 in pancreatic tissue were up-regulated (2.11 ± 0.03 vs 1.70 ± 0.08, 9 420 ± 624 vs 4 973 ± 577),but LAMP-2 was down-regulated(20 533 ± 578 vs 23 231 ± 1 155). Compared with ANP group,the proteins expression levels of LC3Ⅱ/Ⅰand p62 in HANP group was obviously decreased (20 533 ± 578 vs 23 231 ± 1 155), and the difference was statistically significant (all P<0.05). Conclusions Hypertriglyceridemia can worsen the pathology injury of AP,and the mechanism may be related to the decreased autophagy related proteins LC3Ⅱ/Ⅰ and p62 and decreased number of autophagosome.