乌司他丁对脓毒症大鼠肠粘膜凋亡和细菌移位的影响

Effects of ulinastatin on gut mucosal apoptosis and bacterial translocation in rats with sepsis

目的探讨乌司他丁(UTI)对脓毒症大鼠肠粘膜凋亡和细菌移位的影响。方法将50只SD大鼠随机分为对照组(n=5)、脓毒症组(n=15)、预处理组(n=15)及治疗组(n=15)。脓毒症组、预处理组及治疗组利用盲肠结扎打孔法(CLP)制作大鼠脓毒症模型,预处理组在CLP前2h经尾静脉注射UTI25000U/kg,治疗组在CLP后2h经尾静脉注射UTI25000U/kg。分别在CLP后3、6及12h活杀大鼠,取回肠黏膜及全血标本行小肠粘膜病理光镜观察、Tunel法检测小肠黏膜细胞凋亡指数及PCR扩增全血大肠杆菌DNA。结果脓毒症组小肠绒毛顶端上皮脱落,固有层崩解,毛细血管出血和溃疡形成,治疗组和预处理组能显著减轻上述改变;脓毒症组较其他三组比较小肠黏膜细胞凋亡指数有显著增高(P<0.05),CLP后12h预处理组较治疗组比较在上述指标有显著性差异(P<0.05),脓毒症组及治疗组全血大肠杆菌DNA检测阳性,对照组和预处理组阴性。结论脓毒症时肠黏膜凋亡明显增加,肠细菌移位;乌司他丁可显著减轻脓毒症大鼠肠道黏膜凋亡,抑制肠细菌的移位。

Objective To investigate the effects of ulinastatin on gut mucosal apoptosis and bacterium translocation in a rat model of sepsis. Methods Fifty rats were randomly assigned into 4 groups, namely the control （n=5, no operation or drugs）, ulinastatin pretreatment （n=15, treated with 25 000 U/kg ulinastatin 2 h before operation）, ulinastatin treatment （n=15, treated with 25 000 U/kg ulinastatin 2 h after operation） and sepsis model （n=15, without drug treatment） groups. The rats in the later 3 groups were subjected to cecal ligation and puncture （CLP）. At 3, 6 and 12 h after CLP, the rats were sacrificed and the ileum was removed to examine the pathology and apoptosis of the mucosa. The DNA of Bacillus coli in the whole blood was detected using PCR. Results Sepsis caused of epithelial cell loss in the ileal villi, ulceration and blebbing of the lamina propria. Ulinastatin treatment administered before and after the operation both significantly alleviated these morphological anomalies. The sepsis rats showed significantly increased intestinal mucosal apoptotic index as compared with the other 3 groups （P〈0.05）. Ulinastatin pretreatment, in comparison ulinastatin treatment 12 h after CLP, significantly increased the intestinal mucosal apoptotic index （P〈0.05）. Bacillus coli DNA was positive in sepsis and postoperative ulinastatin treatment groups but negative in the control and pretreated groups. Conclusion Increased intestinal musocal apoptosis and gut bacterial translocation occur in rats following sepsis, and ulinastatin can effectively decrease intestinal mucosal apoptosis and inhibit bacterial translocation.