Study On The Action Of Nuclear Factor-κB In Rat Acute Necrosis Pancreatitis With Acute Lung Injury Model And The Treatment With "YiYanHeJi

Objectives: Acute pancreatitis (AP), is one of the familiar acute abdominal disease of surgery, which is classified with acute edema pancreatitis and acute necrosis pancreatitis. Acute necrosis pancreatitis is a severe disease, with high mortality and fast clinical development .ANP is not only a local disease, but also a systematic disease. Despite of the pancreatic ischemia and necrosis, manifest clinically as systematically multiple organ dysfunction or multiple organ dysfunction syndrome. Especially the acute lung injury, or acute respiratory distress syndrome, always firstly manifests on patients with acute necrosis pancreatitis. Acute lung injury occurs as a result of a cascade of cellular events initiated by either infectious or noninfectious inflammatory stimuli. An elevated level of proinflammatory mediators combined with a decreased expression of anti-inflammatory molecules is a critical component of lung inflammation. Expression of proinflammatory genes is regulated by transcriptional mechanisms. Nuclear factor-κB (NF-κB) is one critical transcription factor required for maximal expression of manycytokines involved in the pathogenesis of acute lung injury. So the comprehension and regulation to NF-κB may have important significance on the mechanism and tretment of acute lung injury. In this study we investigated Wistar rat model of acute necrosis pancreatitis combined with acute lung injury and treated it with Chinese traditional medicine "YiYanHeJi". We aimed at studying the activation of NF-κB in lung and evaluating the effects of "YiYanHeJi" during the experiment by morphology,pulmonary microvascular permeability index(PI) and immunohistochemistry.Methods: Acute necrosis pancreatitis combined with acute lung injury model was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. 168 healthy Wistar rats, weight 200-250g, randomly divided into 3 groups: model group, YiYanHeJi treated group and negative group, with 56 rats in each group. Put rats to death after operation and treatment at 0.5h, 1h, 2h, 4h, 6h, 12h, 24h, 48h. Determined the pulmonary microvascular permeability index, observed pancreatic and lung issue changes by optical microscopy, checked the activation of NF-kappa B in lung tissue using immunohistochemistry. Analyzed the data with statistic software and protract curve.Results: The acute necrosis pancreatitis combined with acute lung injury experimental model was successfully induced 1h after 5% sodium taurocholate injected into the biliopancreatic duct. Although the PIascended in model and YiYanHeJi treated groups, it declined more rapidly in the YiYanHeJi treated group after 12h (p<0.01) compared with the model group. Pathological changes of general and optical microscopy took on milder inflammation in the YiYanHeJi treated group compared with the model group. The NF-kappa B was activated slightly at 0.5h and increased markedly at 2h to 4h in the model and YiYanHeJi treated groups. But it was higher in the model group compared with YiYanHeJi treated group and the saline solution group. The activation of NF-kappa B changed with the time going. The morphological of lung was paralleled with the changing of the activation of NF-kappa B.Conclusions: The methods of retrograde injected 5% sodium taurocholate into the biliopancreatic duct to induce acute necrosis pancreatitis combined with acute lung injury experimental model is simplified, duplicated and valuable. Treatment with YiYanHeJi could inhibit the activation of lung NF-κB, reduce pulmonary microvascular permeability index and smooth the lung inflammation. YiYanHeJi had effective treatment on ALI deduced by ANP, while the activation of NF-kappa B played a key role in the development of disease. The therapy mechanism of YiYanHeJi on ANP with ALI might correlate with the inhibit effect of the NF-kappa B activation.