| Severe acute pancreatitis (SAP) is a serious disease with high morbidity in clinic. For the sudden occurring and rapid progressing, it always leads to significant mortality which is up to 20%~30%.Up to now, the complete pathogenesis of severe acute pancreatitis remains poorly understood and the treatment still remains nonspecific and primarily supportive. Finding a cheaper and more effective drug to reduce the high mortality of SAP is a serious task for us.Now several theories have been proposed to explain the pathogenesis: the most common cause of pancreatitis is the obstruction of bile duct by gallstone or something else. The bile duct and the pancreatic duct have the common opening which leads to the duodenum. Once the common duct is obstructed, bile will be perfused into the pancreas and activate pancreatic protein enzymes, which leads to autolysis and destruction of pancreas. This is also the most classic hypothesis of pancreatitis. And the theory also considers the invasion of pancreatic enzymes into the blood as the chief cause of SAP. But death is often the result of multiple organ dysfunction. Drugs which inhibit pancreatic enzymes don't work well. What is the problem? Many new hypothesis appears, such as "over-activation of leukocyte", "ischemia of pancreas and obstacle of microcirculation", "translocation of bacteria and followed infection". In 1988, Rindernecht suggested that over-activation of leukocyte was the chief cause of SAP, autolysis of pancreas caused by pancreatic enzymes maybe acted in part. Many researches have indicated that the inflammatory response is initiated by injured pancreatic acinar cells which produces inflammatorymediators,such as cytokines (e.g.,TNF-a ) and adhesion molecules (e.g.,ICAM-l), ultimately leading to systemic complications. Blocking the activation of these mediators by using various approaches ameliated pancreatitis in different experimental models.Considering the central importance of the inflammatory response in pancreatitis, therapeutic strategies should be aimed at the key steps leading to this response.Because of the multitude of cytokines, chemokines, and other inflammatory molecules involved in this disease process, one can argue that the most effective strategy should target upstream "master regulators" of these molecules.Recent data suggests that one such key regulator is NF-KB. NF-KB comprises a family of transcription factors regulating the inflammatory, immune, and cell death response. In unstimulated cells, NF-icB is kept in inactive in the cytoplasm by association with the inhibitory(IicB) proteins.On activation, NF-KB translocates into the nucleus and activates the expression of a multitude of genes that have KB-binding sites in their promoters or enhancers. NF-icB activation, at least in part, regulates the expression of cytokines(TNF-a,IL-6),chemokines(IL-8,KC),and other inflammatory molecules such as ICAM-1 and the inducible nitric oxide synthase, all of which are upregulated and play an important role in pancreatitis. There are many NF-icB inhibitors which is proved to be effective in vitro and in vivo.Recent studies indicate that the bioflavonoid curcumin inhibits NF-icB activation in a number of cell types. Compared with other inhibitors,it is more cheaper, more advantage activities and less reverse effects. Curcumin may be a promising drug to ameliorate pancreatitis. In 2003,Gukovsky ameliorated ethanol and CCK induced pancreatitis by curcumin in rats.But the most common cause of pancreatitis in china is bile-duct diease. That whether curcumin is also useful to sodium taurocholate-induced pancreatitis is not reported in the world.In this study,we perfused Sodium taurocholate into the rat's bilio-pancreatic ductto form a classic hemorrhagic pancreatitis model. And treated rats with normal saline, octreotide and curcumin. 6h after the operation, we harvested serum and ascites for amylase and CRP test.The pancreas were also harvested for pathological examination. The differences of amylase ,CRP and pathological change betwee...
|
PDF Full Text Request