| Objective: To study the dynamic changes and effect of p65, an important subtype of nuclear transcription factor-κB (NF-κB) in the pancreas of sodium taurocholic acid-induced severe acute pancreatitis (SAP),and to assess the preventive effects of pioglitazone, a ligand of Peroxisome proliferator-activated receptor gamma, on the development of STC-induced severe acute pancreatitis.METHODS: 130 Male Sprague-Dawley(SD) rats (160-200g) were randomly allocated into two parts:(1) Male Sprague-Dawley(SD) rats (160-200g) were randomly allocated into five groups(n=8 for each group): (a) SAP group. Acute pancreatitis(AP) was induced in male SD rats by the retrograde injection of 1ml/kg.m of 50 g/L sodium taurocholate (STC) in the pancreatic duct. 10% dimethyl sulphoxide (DMSO) was injected intraperitoneally two hours prior to STC; (b) Pioglitazone groups (same as SAP group, but 10% DMSO was replaced by pioglitazone administered intraperitoneally, 2mg/100g,5mg/100g,10mg/100g in DMSO); (c)Sham operation group. Sham-operated animals served as control. Operation was executed, STC was not injected, but pancreas was flipped and striked gently three times. After operation, rats were given freedom to drink water, but were fasted.The survival time and survival rate of each group were compared .(2)Male Sprague-Dawley(SD) rats (160-200g) were randomly allocated into five groups(n=18 for each group): (a) SAP group. Acute pancreatitis(AP) was induced in male SD rats by the retrograde injection of 1ml/kg.m of 50 g/L sodium taurocholate (STC) in the pancreatic duct. 10% dimethyl sulphoxide (DMSO) was injected intraperitoneally two hours prior to STC; (b) Pioglitazone groups (same as SAP group, but 10% DMSO was replaced by pioglitazone administered intraperitoneally, 2mg/100g,5mg/100g,10mg/100g in DMSO); (c)Sham operation group. Sham-operated animals served as control. Operation was executed, STC was not injected, but pancreas was flipped and striked gently three times. After operation, rats were given freedom to drink water, but were fasted. Rats were killed by abdominal aorta exsanguination at 3,6 and 12h after the inducetion of pancreatitis. Serum and ascitic activities of amylase were measured .The pancreatic tissue was divided into two parts: I,Samples of pancreatic tissues for histological examination were fixed in 10% formalin and stained with hematoxylin and eosin,and histologic score was performed. II,Samples of pancreatic tissues were rapidly frozen in liquid nitrogen and stored at -80℃for analysis against p65.RESULTS:(1) The survival time of Pioglitazone group(5mg/100g) was longer than that of SAP group(P<0.05), while lower than that of sham group(P<0.05). The 36-hour survival rate in of Pioglitazone group(5mg/100g) was longer than that of SAP group(P<0.05), while lower than that of sham group(P<0.05).(2) The concentration of serum amylased and ascite amylased in SAP group were significantly higher than those in sham group (P<0.001). Pioglitazone administered(2mg/100g,5mg/100g,10mg/100g i.g.) 2 hours prior to STC,attenuated dose-dependently the pancreatic tissue damage in STC-induced pancreatitis as demonstrated by the improvement of pancreatic histology,reduce ascitic activities of amylase, the concentrations of inflammatory cyctokines ( IL-6) of the serum and increased serum levels of IL-6.(P<0.01 or P<0.05).(3) The concentration of the pancreatic histologic score in SAP group were significantly higher than those in sham group (P<0.001).According to Schmidt criteria, the pancreatic histologic score showed that there existed significant difference in the SAP group in the interstitial edema, inflammatory infiltration, parenchyma necrosis and parenchyma hommorrhage in comparison with those of the sham group and pioglitazone groups respectively (P<0.01, P<0.05) .(4) The activity of NF-κB p65: In A group and Pgroup,the activity of NF-κB p65 was markedly upgraded compared with C group at all pionts (P<0.01),which was decreased significantly in P2 group compared with A group (P<0.05) at 6h and 12h.Conclusions:(1) The results of our study demonstrate that pioglitazone could raise the 36-hour survival rate and prolong survival time.(2) IL-6 is the reaction of the severity of acute pancreatitis reliable indicators, studies show that it is in parallel between the level of severity of acute pancreatitis and IL-6, when the effective inhibition of NF-κB activity, IL-6 decreased significantly(3) NF-κB is involved in the inflammation response of SAP. The expression of NF-κB has a positive correlation with pathology damage of pancreatic tissue. Inhibition of the expression of NF-κB in pancreatic tissue can be helpful for treatment of SAP by downregulating the above cytokines.(4) Through activation of PPARγway Pioglitazone, inhibiting NF-κB activity and reducing inflammation in rats SAP, is expected to become a new kind of treatment methods SAP...
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