Abstract: Objective  To investigate the effect of hemodiafiltration (HDF) on the intestinal injury of severe acute pancreatitis (SAP) rats and the Keap1/Nrf2 signaling pathway.  Methods  Sprague-Dawley (SD) rats were randomly divided into sham operation group (n=18), SAP group (n=18) and HDF group (n=18). Open surgery without SAP manipulation was performed in sham operation group, SAP model was performed in SAP group and HDF group, and continuous HDF for 12 hours was conducted immediately after the preparation of SAP model in HDF group. The expressions of apoptotic factors Bax and Bcl-2,  Keap1/Nrf2 signaling pathway-related proteins in intestinal epithelial cells, endotoxin level in plasma of portal vein, and bacterial culture were assayed after the operation.  Results  In SAP group, the expression of Bax in intestinal epithelial cells was higher than that in sham operation group (t=8.083, P=0.001), while the expression of Bcl-2 in intestinal epithelial cells was lower than that in sham operation group (t=4.765, P=0.008); plasma endotoxin of portal vein and positive rates of bacterial culture of pancreas and liver were higher than those in sham operation group (plasma endotoxin at 12h: t=15.110, P＜0.001; at 24h: t=19.050, P＜0.001; at 48h: t=18.330, P＜0.001. positive bacterial culture of pancreas at 12h: t=23.712, P＜0.001; at 24h: t=20.901, P＜0.001; at 48h: t=36.740, P＜0.001. positive bacterial culture of liver at 12h: t=23.983, P＜0.001; at 24h: t=29.692, P＜0.001; at 48h: t=35.694, P＜0.001). In HDF group, the expression of Bcl-2 in intestinal epithelial cells was higher than that in SAP group (t=5.825, P=0.004); the expression of Bax in intestinal epithelial cells, plasma endotoxin of portal vein and positive rates of bacterial culture of pancreas and liver were lower than those in SAP group (Bax: t=6.796, P=0.002. plasma endotoxin at 12h: t=6.235, P=0.003; at 24h: t=12.251, P＜0.001; at 48h: t=12.980, P＜0.001. positive bacterial culture of pancreas at 12h: t=16.470, P＜0.001; at 24h: t=5.950, P=0.004; at 48h: t=15.071, P＜0.001. positive bacterial culture of liver at 12h: t=2.782, P=0.049; at 24h: t=9.790, P＜0.001; at 48h: t=15.172, P＜0.001). In SAP group, the expressions of Keap1 and Nrf2 were lower than those in sham operation group (Keap1: t=11.611, P＜0.001; Nrf2: t=12.241, P＜0.001). In HDF group, the expressions of Keap1 and Nrf2 were higher than those in SAP group (Keap1: t=80.658, P=0.001; Nrf2: t=12.312, P=0.000).  Conclusion  Continuous HDF can improve the permeability of intestinal epithelial cells and intestinal dysfunction, and inhibit endotoxin and bacterial translocation in SAP rats.

Key words: Continuous hemodiafiltration, Severe acute pancreatitis, Keap1/Nrf2 pathway, Mucosal epithelial cells