芒硝外敷联合乌司他丁对胰腺炎大鼠肠屏障功能、胰腺细胞活性及PI3K/Akt/mTOR信号的影响

目的 探讨芒硝外敷联合乌司他丁对胰腺炎大鼠肠屏障功能、胰腺细胞活性及PI3K/Akt/mTOR信号的影响。方法 选取50只SPF级SD雄性大鼠，随机分为正常（N）组，模型（M）组，芒硝外敷（G）组，乌司他丁（U）组，芒硝外敷+乌司他丁（O）组，每组10只，对M组、G组、U组、O组采用开腹经胰胆管逆行性注射5%牛黄胆酸钠法建立胰腺炎模型，N组不建立该模型，建模成功后，对G组腹部给予芒硝外敷，对U组腹腔注射乌司他丁5万U/kg，对O组腹部给予芒硝外敷和腹腔注射乌司他丁5万U/kg，N组、M组同期给予腹腔注射同体积生理盐水，HE法检测胰腺组织病理形态，电镜检测肠屏障功能，TUNEL法检测胰腺细胞凋亡，免疫印迹法检测PI3K/Akt/mTOR信号相关蛋白表达。结果 与N组相比，M组可见胰腺组织明显病理变化及肠屏障功能损伤，与M组比较，G组、U组、O组病理形态及肠屏障功能明显改善，且O组改善最为明显；与N组相比，M组大鼠肠粘膜损伤程度、胰腺组织中PI3K、p-Akt、p-mTOR蛋白表达显著升高，胰腺细胞凋亡水平显著降低（均P<0.05），与M组比较，G组、U组、O组大鼠肠粘膜损伤程度、胰腺组织中PI3K、p-Akt、p-mTOR蛋白表达显著降低（均P<0.05），胰腺细胞凋亡水平显著升高（P<0.05），且U组与 G组相比差异无统计学意义（P＞0.05），O组比U组变化明显（P<0.05）。结论 芒硝外敷联合乌司他丁可显著改善胰腺炎大鼠肠屏障功能及胰腺细胞活性，并显著抑制PI3K/Akt/mTOR信号

Effects of mirabilite external application combined with ulinastatin on intestinal barrier function, pancreatic cell activity and PI3K/Akt/mTOR signal in rats with pancreatitis

Objective To investigate the effects of mirabilite external application combined with ulinastatin on intestinal barrier function, pancreatic cell activity and PI3K/Akt/mTOR signal in rats with pancreatitis. Methods Fifty SPF SD male rats were randomly divided into normal (N) group, model (M) group, glauberatin external application (G) group, ulinastatin (U) group, and glauberatin external application + ulinastatin (O) group, with 10 rats in each group. The model of pancreatitis was established in groups M, G, U and O by retrograde injection of 5% sodium taurine cholate through pancreatic duct. Group N does not build this model. After the modeling was successful, group G was given external application of glauberatin, group U was given intraperitoneal injection of ulinastatin 50,000 U/kg, group O was given external application of glauberatin and intraperitoneal injection of ulinastatin 50,000 U/kg, group N and group M were given intraperitoneal injection of normal saline of the same volume at the same time. The histopathologic morphology of pancreas was detected by HE method. The intestinal barrier function was detected by electron microscopy. Pancreatic cell apoptosis was detected by TUNEL assay. The expression of PI3K/Akt/mTOR signal-related proteins was detected by Western blotting. Results Compared with group N, the pathological changes of pancreatic tissue and intestinal barrier function were observed in group M. Compared with group M, the pathological morphology and intestinal barrier function of group G, group U and group O were significantly improved, and the improvement of group O was the most obvious. Compared with group N, the intestinal mucosal injury degree and the protein expressions of PI3K, p-Akt and p-mTOR in pancreatic tissue of rats in group M were significantly increased (P<0.05), and the apoptosis level of pancreatic cells was significantly decreased (P<0.05). Compared with group M, the intestinal mucosal injury degree and the protein expressions of PI3K, p-Akt and p-mTOR in pancreatic tissue of groups G, U and O were significantly decreased (P<0.05), and the apoptosis level of pancreatic cells was significantly increased (P<0.05), and there was no significant difference between group U and group G (P> 0.05). The changes in group O were significantly higher than those in group U (P<0.05).Conclusion External application of Mirabilite combined with ulinastatin can significantly improve intestinal barrier function and pancreatic cell activity in rats with pancreatitis, and significantly inhibit PI3K/Akt/mTOR signal