Role Of Resistin In The Pathogenesis Of Acute Pancreatitis And The Prophylactic And Therapeutic Treatments With Rosiglitazone

Partâ… The Induction of Rat Models of Acute Edema Pancreatitis and Necrotic Pancreatitis.Objective To induce simple and easier replicated rat models of acute edema pancreatitis (AEP) and acute necrotic pancreatitis (ANP). Provide rat models for the second, the third and the forth parts of this study. Methods Forty Sprague-Dawley rats were randomly divided into four groups, control group, sham opertation group, AEP group and ANP group. AEP model was induced by intraperitoneal injection of cerulein and ANP model was induced by intraperitoneal injection of L-arginine while the control group didn't receive anything, the sham opertation group received same volume injections of 0.9% saline solution. Amylase in blood plasma and pancreas/body weight ratio were evaluated and pancreatic pathology was recorded. Results The amylase and the pancreas/body weight ratio increased significantly in both AEP and ANP groups (P<0.001) and higher in ANP group (P<0.05). The pathology of pancreas in AEP group showed interstitial edema, inflammatory cells infiltration and acini swelling while in ANP group, the histological changes were more severe include acinar cell necrosis and bleeding. Conclusions Intraperitoneal injection of cerulein and L-arginine can induce AEP and ANP.Partâ…¡The Role of Resistin in the Pathogenesis of Acute Pancreatitis. Objective To study the role of resistin in the pathogenesis of acute pancreatitis. Methods Forty Sprague-Dawley rats were randomly divided into four groups, control group, sham operation group, AEP group and ANP group. AEP model was induced by intraperitoneal injection of cerulein and ANP model was induced by intraperitoneal injection of L-arginine while the control group didn't receive anything, the sham opertation group received same volume injections of 0.9% saline solution. Amylase, resistin, CRP, TNF-alpha, IL-1belta in blood serum and pancreas/body weight ratio were evaluated and pancreatic pathology was recorded. The level of resistin was detected in pancreas by immunohistochemistry. The gene expression of resistin mRNA was investigated by realtime-PCR. Results The levels of amylase, resistin, CRP, TNF-alpha and IL-1belta were significantly increased in both AEP and ANP group (P<0.01) and higher in ANP group (P<0.001). Compared to control group and sham operation group, the level of the mRNA of resistin was also markedly increased in both pancreatitis groups (P<0.01) and higher in ANP group (P<0.05). The increase of CRP, TNF-alpha and IL-1belta was correlated with resistin, and the resistin's increases was correlated with the pathologic severitity of pancreatitis. The level of CRP was correlalted with the the pathologic severitity of pancreatitis. Resistin localized to endochylema of pancreatic cell. Conclusions The data support the notion of an intrisinc resistin in the rat pancreas and the resisitin in blood serum was activated in acute pancreatitis. The resistin may activate other cellular factors TNF-alpha and IL-1belta and play a role in the pathogenesis of acute pancreatitis. The resistin was correlated with the severitity of pancreatitis.Partâ…¢The Effect of Recombination resistin upon the cytokine in the Acute PancreatitisObjective To study the effect of recombination resistin upon the cytokine in the acute pancreatitis. Methods Forty Sprague-Dawley rats were randomly divided into four groups, AEP group, AEP+resistin, ANP and ANP+resistin group. AEP model was induced by intraperitoneal injection of cerulein and ANP model was induced by intraperitoneal injection of L-arginine. the AEP+resistin and the ANP+resistin group were injected recombination resistin by caudal vein while the AEP and ANP group were injected 0.9% saline solution. TNF-alphaand IL-1belta in blood serum were examinated. Results The levels of TNF-alpha and IL-1belta wrer significantly increased in both AEP+resistin group and ANP+ resistin group (P<0.01).Conclusions In the acute pancreatitis, the recombination resistin can reinforce the releases of the cytokine TNF-alpha, IL-1belta and can aggravate the pathogenetic of the acute pancreatitis.Partâ…£Prophylactic and Therapeutic Treatments with Rosiglitazone Ameliorate Acute Necrotic Pancreatitis and Pancreatitis-Associated Pulmonary Injury.Objective To prove the protective effects of rosiglitazone on acute pancreatitis and pancreatitis-associated pulmonary injury. Method Forty Sprague-Dawley rats were randomly divided into four groups, control group, ANP group, prophylactic treatment group and therapeutic treatment group. In the pancreatitis group, rats were given two intraperitoneal injections of L-arginine while the controls received same volume injections of 0.9% saline solution. For the prophylactic treatment groups, rats were injected bolus with rosiglitazone two times at an hour interval 60min prior to the induction of pancreatitis. For the therapeutic treatment groups, animals were injected with rosiglitazone two times at an hour interval 60min after the induction of pancreatitis. Amylase, resistin, TNF-alpha and IL-1belta in blood plasma, lung myeloperoxidase, pancreas/body weight ratio and lung wet/dry weight ratio were evaluated. Pancreatic and pulmonary pathology were observed. The gene expression of resistin mRNA was investigated by real-time PCR. Results Both prophylactic and therapeutic treatments with rosiglitazone could ameliorate pancreatic and pulmanory injury induced by L-arginine, as observed by biochemical and histopathological study (P<0.01). The protective action of rosiglitazone was linked to inhibitions of TNF-alpha and IL-1belta increases (P<0.01), and decreased the level of resistin in plasma and the mRNA levels of resistin in pancreas (P<0.01). Conclusions Rosiglitazone ameliorates acute pancreatitis and pancreatitis-associated pulmonary injury in both prophylactic and therapeutic uses. This protective action may come from the inhibition of resistin and thus the decreases of other cellular factors.