Experimental Study Of Intestinal Injury Complicated By Severe Acute Pancreatitis And Intervene At Plateau Hypoxia Environment

Part I Experimental Study of Intestinal Injury Complicated by Severe Acute Pancreatitis at Plateau Hypoxia EnvironmentObjective:To observe of rat intestinal mucosal tissue injury complicated by severe acute pancreatitis (SAP) at plateau hypoxia environment, and investigate the mechanism of gut barrier injury complicated by SAP at high plateau (H-SAP). Method:First,48Wistar rats were randomly divided into2groups (n=24in each group) according different altitude:Xi’an group(X) and Maxianshan group(M), every group was subdivided into four subgroups(n=6in each group), sham-operation group, SAP-6h group, SAP-12h group and SAP-24h group.4%sodium taurocholate was injected into the pancreatic duct to induce SAP. The rats of SAP group were sacrificed at6h,12h and24h after4%sodium taurocholate injection, and the rats of SO group were sacrificed at6h after operation. Pancreas and intestinal tissues were harvested to observe the pathological changes, The content of TNF-a and IL-10in intestine were measured respectively. The ultrastructure change of intestinal mucosa were observed under transmission electron microscope. Results:Compared with the SO group, content of TNF-a and IL-10in intestine were significantly higher (P<0.01) in the SAP group. There was a significantly difference (P<0.05) when content of TNF-a and IL-10were compared among SAP groups at each time point. In the light microscopy, Pancreas and bowel organization structure of SO group were normal, there was no significant difference (P>0.05); the intestinal tissue pathological scores were significantly higher in the M-SAP group than the X-SAP group (P<0.05). The electron microscopy revealed that the intestinal mucosal injury was more severe in the M group than the X group at each time point. Results TEM showed that the ultrastructure damage of M-SAP group more serious than X-SAP group. Conclusion:Intestinal tissue injury generally complicated by SAP. Furthermore, the Plateau Hypoxia Environment can induce and aggravate the intestinal mucosal barrier injury under H-SAP, the percentage of TNF-a and IL-10disturbance may closely relate with pathogenesis and prognosis of H-SAP. Part II Effect of Dahuang Gancao decoction on intestinal tissue injury complicated by severe acute pancreatitis at plateauObjective:To investigate the intervention effects of dahuang gancao decoction on intestinal tissue injury complicated by severe acute pancreatitis at plateau. Methods:54Wistar rats were transported to Lanzhou Maxianshan (elevation3848m) from Lanzhou City, after20days acclimatization,they were randomly divided into3groups(n=18in each group),namely sham-operated group (SO), SAP group(SAP), dahuang gancao decoction intervention group (DG).4%sodium taurocholate was injected into the pancreatic duct to induce SAP.Dahuang gancao decoction(0.25g/ml)0.6ml/100g weight was gavaged in the DG.the same volume of normal saline was gavaged in the SO and SAP group, which was repeated12h later. After6h,12h,24h, all rats were sacrificed, pancreas and intestinal tissues were harvested to observe the pathological changes.The ultrastructure change of intestinal mucosa were observed under transmission electron microscope. Results:In the SO group, content of TNF-a and IL-10in intestine of were not significantly change; In the SAP group and DG group, TNF-a in intestine raised in a time-dependent manner, but IL-10level gradually reduced in a time-dependent manner, compared with the SO group, content of TNF-a and IL-10was significantly higher in SAP group and DG group (P<0.01); Compared with the SAP group, content of TNF-a reduced significantly in RG group(P<0.05), and content of IL-10is increased significantly (P<0.05). In the light microscopy, Pancreas and bowel organization structure are normal, there was no significant difference at each time point (P>0.05); compared with the the SO group, the severity of pancreas and intestine Pathological damage significantly increased in the SAP group and DG group with a time-dependent manner. But pathological score of the DG group decreased significantly when compared with SAP group. Pancreatic and intestinal tissue pathological score was positively correlated(r=0.796,P<0.01). Under the transmission electron microscope, intestinal epithelial structure was normal in the SO group, and the intestinal mucosal injury was severe in the SAP group and the DG group; But compared with the SAP group,There was alleviated markedly in the DG rroup.Conclusion:Dahuang gancao decoction can quickly improve intestinal injury complicated by severe acute pancreatitis at plateau, and the mechanism may be associated with inhibiting the expression of TNF-α and increasing the expression of IL-10.