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"Adipose Cells-macrophages Interaction" In The Obese Severe Acute Pancreatitis Study Of The Pathogenesis

Posted on:2015-06-17Degree:MasterType:Thesis
Country:ChinaCandidate:F YangFull Text:PDF
GTID:2284330431974112Subject:Internal Medicine
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Severe acute pancreatitis(SAP) is common clinical critical disease. At present, it is widely believed that inflammatory factor freed by activated macrophagocyte and subsequent cascade effect is the key for pancreatitis grow from local inflammation and then develop to life threatening systemic inflammation.As is well-known, inflammatory factor (TNF-α、IL-6etc) released by adipose tissue in obesity participate in inflammation reaction of type2diabetes mellitus, hypertension and so on. In grade of APACHE-Ⅱ, obesity as an independent risk factor for acute pancreatitis, has been listed as one of the estimate the prognosis of acute pancreatitis index. But the high level of free fatty acids caused by obesity itself is not associated with the severity of SAP, the occurrence of obesity in SAP and the specific mechanism affected the prognosis remains to be further research.Objective:From clinical problem "why obese people are more likely to happen in severe acute pancreatitis", we take macrophages as an important immune cells participate in severe acute pancreatitis as the center, research the interaction of obese people adipose tissue and macrophages, Delve into the possible mechanism of adipose tissue involved in SAP and the outcome, fat cell-macrophage positive feedback regulation (quantity), fat cells induced macrophage polarized state phenotype transformation (activated), to clarify the pathogenesis, prognosis and outcome of severe acute pancreatitis in obese, find out suitable targets for clinical therapy.Methods:Adopted by retrograde injection of5%sodium taurocholic acid in pancreas and established severe acute pancreatitis in rats, set up obesity model by high fat feed, divided into four groups:sham-operation normal weight group, severe acute pancreatitis group, sham-operation obesity group, severe acute pancreatitis obesity group. Rats from each group (24h after established model) remove the pancreatic tissue grade for pathology score, remove the fat tissue and then take out RT-PCR, Western Blot, immunofluorescence respectively to detect expression of F4/80and EL-6、 TGF-β1in macrophages, remove the liver tissue PCR to detect the expression of F4/80, MCP-1.Results:(1)Obesity SAP pancreatic pathology score higher than the sham-operation obesity group, differences are statistically significant (P<0.01). Obesity SAP pancreatic pathology score higher than in SAP group, differences are statistically significant (P<0.05). SAP pancreatic pathology score were higher than that of sham-operation normal weight group, differences are statistically significant (P<0.05).(2)Obesity SAP compared with obese control of F4/80expression is reduced in adipose tissue, differences are statistically significant (P<0.01). Obesity in SAP and the SAP group compared to the expression of the F4/80is reduced in adipose tissue, difference is not statistically significant (P>0.05). SAP group compared with control group the F4/80is reduced in adipose tissue, difference is not statistically significant (P>0.05).(3)Obesity SAP compared with control group IL-6expression is increased in adipose tissue, differences are statistically significant (P<0.05).(4)Obesity in SAP group compared with obese control reduced TGF-J31expression in adipose tissue, differences are statistically significant (P<0.05). Obesity in SAP group compared with SAP group the TGF-β1expression is increased in adipose tissue, difference is not statistically significant (P>0.05). SAP compared with control group TGF-β1expression is increased in adipose tissue, differences are statistically significant (P<0.05).(5)Obesity SAP group compared with control obesity group the F4/80expression is increased in liver, difference is not statistically significant (P>0.05). Obesity in SAP group compared with SAP group F4/80expression is reduced in the liver, differences are statistically significant (P<0.05). SAP group compared with control group the F4/80expression is increased in the liver, differences are statistically significant (P<0.05).(6)Obesity SAP group compared with control group elevated the MCP1expression in the liver, differences are statistically significant (P<0.05). Obesity SAP compared with SAP group MCP1expression is lower in the liver, differences are statistically significant (P<0.05). SAP group compared with control group MCP1expression is increased in the liver, differences are statistically significant (P<0.05).(7)3h and6h, Obesity SAP group compared with control group the F4/80expression is reduced in the adipose tissue, differences are statistically significant (P<0.05).Conclusions:Utilizes the pancreatic retrograde injection of5%sodium taurocholic acid can create severe acute pancreatitis model in rats. The sham-operation control group macrophage M2polarization produce anti-inflammatory factor (TGF-β1). Obesity in severe acute pancreatitis, macrophage Ml polarization produce proinflammatory factor (such as IL-6), participate in pancreatitis inflammation. Macrophages in adipose tissue of thin rats is given priority to M2polarization state, macrophages in adipose tissue of obesity rats is given priority to Ml polarization state, macrophages in obesity SAP is given priority to Ml polarization state.Obesity in severe acute pancreatitis and severe acute pancreatitis, macrophages number decreased in adipose tissue, macrophages number increase in liver tissue, regard as inflammation is transferred to the liver.
Keywords/Search Tags:Severe acute pancreatitis, Obesity, Adipose tissue macrophages, M1polarization, M2polarization
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