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Alprostadil Inhibits Acute Pancreatitis In Rats By Down-regulating The JAK2/STAT3 Signaling Pathway

Posted on:2020-06-24Degree:MasterType:Thesis
Country:ChinaCandidate:L XiangFull Text:PDF
GTID:2434330578969721Subject:Clinical Medicine
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Objective:To investigate the difference of AP model induced by sodium taurocholate,L-arginine and bombesin in Sprague Dawley(SD)rats,and to evaluate the effect of modeling by pancreatic pathological tissue score and serum biochemical level.In order to further find out the best experimental model of acute pancreatitis and the best time point of modeling.Method:128 male SD rats were randomly divided into 4 groups: group A: blank control group;group B: caerulein induced group;group C: l-arginine group;group D: sodium taurocholate group.Group A was injected intraperitoneally with 0.9% normal saline,and group B was injected intraperitoneally with 50ug/kg caerulein after Rana chensinensis peptide was dissolved in 0.9% normal saline at intervals of 1 hour for 6 times.The rats in group C were injected intraperitoneally with 20% L-arginine solution configured with 0.9% normal saline at a dose of 2.5 g / kg,once at intervals of 1 h,for a total of 2 times.Group D was treated with retrograde injection of 5% sodium taurocholate through duodenal pancreaticobiliary duct at the dose of 50mg/kg.Pancreatic samples and blood were collected at 6 hours,12 hours,24 hours and 48 hours after the last drug injection.The biochemical indexes were AMY and LPS,pancreatic specimens were stained with HE and scored by pancreatic pathological tissue score.The experimental data were processed by SPSS18.0 statistical software.t test and analysis of variance showed that the difference was statistically significant.Result :(1)All three methods can successfully induce AP model.(2)The AP model induced by cerulein is light,noninvasive,simple and reproducible.it is an ideal model for mild acute pancreatitis.(3)Arginine can induce SAP model,which is noninvasive,simple and reproducible.it is an ideal model for SAP.(4)Sodium taurocholate can induce SAP model,which is an ideal SAP model with organ necrosis because of its tedious operation,high requirement of aseptic environment,serious disease and high fatality rate.(5)The comparison of AP,established by these three methods at the same time point,the lightest was cerulein induction group,followed by arginine induction group,the most serious was sodium taurocholate induction group.(6)With the passage of time,the pathological score of pancreatic tissue was the highest in bombesin induction group and arginine induction group at 48 h,which indicated that pancreatitis was the most serious,but there was local self-healing,while sodium taurocholate induction group increased with time.The more serious the pancreatic injury,and no self-healing trend,and fatal.Conclusion:L-arginine induction and 48 h were the most practical ways to induce AP model and the best time to use L-arginine,respectively..Objective:To explore the effect and mechanism of alprostadil on acute AP in rats.Methods:Forty healthy clean SD rats were randomly divided into blank group(group A),model AP group(group B),alprostadil experimental group(group C),AG490 experimental group(group D),alprostadil + AG490 Experimental group(group E).An animal model of acute pancreatitis was established by intraperitoneal injection of 20% L-arginine.The alprostadil experimental group,the AG490 Experimental group and the alprostadil + AG490 experimental group were respectively injected with alprostadil,AG490 and alprostadil + AG490 30 minutes before modeling.The rats in each group were killed 48 hours after the establishment of the model.The pathological changes of pancreas in each group were observed and scored by HE staining.Detection of serum amylase and lipase in each group,The levels of serum IL-1?,IL-6 and TNF-? in serum of each group were detected by ELISA,and the protein levels of p-JAK2 and p-STAT3 in pancreatic tissue of rats in each group were detected by Western blot.Result:The levels of serum amylase,lipase,IL-1 ?,IL-6 and TNF-? in model group were significantly higher than those in the blank group,and pancreatic pathological scores in the model group were significantly higher than those in the blank group at the same time.The indexes in alprostadil treatment group,AG490 intervention group and alprostadil + AG490 intervention group were significantly lower than those in the model group,while those in the alprostadil + AG490 intervention group were the lowest,The level of protective inflammatory factor IL-10 is compared with the above three inflammatory factors,and the results show the opposite.At the same time,compared with the blank group,the protein levels of p-JAK2 and p-STAT3 in the model group were significantly up-regulated.The protein levels of p-JAK2 and p-STAT3 were significantly decreased after pretreatment with alprostadil and AG490,and the effect of pretreatment with alprostadil and AG490 was better.Conclusion:Alprostadil participates in AP through JAK2/STAT3 signal transduction pathway and plays an important protective role in AP.
Keywords/Search Tags:Cerulein, L-arginine, sodium taurocholate, acute pancreatitis, Alprostadil, JAK2/STAT3 signal.transduction pathway
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