目的:观察大黄附子汤(DHFZT)对早期重症急性胰腺炎肠黏膜机械屏障的影响。方法:24只雄性SD大鼠采用随机数字表法分为4组：假手术(SH)组、假手术-DHFZT(SH-DHFZT)组、重症急性胰腺炎(SAP)组、DHFZT治疗(SAP-DHFZT)组，每组6只。SH组、SH-DHFZT组大鼠开腹后，翻动胰腺数次后关腹；SAP、SAP-DHFZT组经胰胆管缓慢逆行注入4%牛磺胆酸钠(1 ml/kg)诱导SAP模型。术后SH、SAP和SH-DHFZT组与SAP-DHFZT组分别用2 ml生理盐水或DHFZT于术后12、24、36 h保留灌肠。检测大鼠血淀粉酶、血钙、内毒素、白细胞介素(IL)-1β，肠黏膜二胺氧化酶(DAO)浓度变化。比较肠黏膜机械屏障紧密连接蛋白Claudin-1、Occludin、ZO-1的表达及肠道病理组织学评分。采用SPSS 22.0软件中单因素方差分析(One-way ANOVA)对数据进行分析。结果:SAP组血清内毒素、淀粉酶、DAO及IL-1β水平高于SH组[内毒素(132.40±8.00) ng/L比(31.70±8.40) ng/L，淀粉酶(1 163.00±71.88) U/L比(174.20±8.89) U/L，DAO(23.11±2.98) μg/L比(10.76±2.42) μg/L，IL-1β(82.20±7.14) μg/L比(25.37±2.38) μg/L，n F＝452.162、1 118.302、62.099、342.100，n P值均<0.05]，差异均有统计学意义，SAP组血钙含量低于SH组[(1.25±0.16) mmol/L比(1.99±0.10) mmol/L，n F＝92.292，n P<0.05]，差异有统计学意义。SAP-DHFZT组血清内毒素、淀粉酶、DAO及IL-1β水平低于SAP组[内毒素(68.80±5.30) ng/L比(132.40±8.00) ng/L，淀粉酶(500.70±54.67) U/L比(1 163.00±71.88) U/L，DAO(13.79±2.93) μg/L比(23.11±2.98) μg/L，IL-1β(63.03±7.27) μg/L比(82.20±7.14) μg/L，n F＝263.544、322.707、29.841、21.235，n P值均<0.05]，差异均有统计学意义，血钙含量高于SAP组[(1.72±0.08) mmol/L比(1.25±0.16) mmol/L，n F＝41.419，n P<0.05]，差异有统计学意义。SAP组大鼠48 h后胰腺及回肠组织结构均发生不同程度破坏，ZO-1、Occludin、Claudin-1表达减弱。经DHFZT治疗后，胰腺及回肠组织结构破坏有修复，肠上皮紧密连接蛋白ZO-1、Occludin、Claudin-1表达高于SAP组(ZO-1为0.80±0.12比0.09±0.02，Occludin为0.69±0.11比0.53±0.11，Claudin-1为0.42±0.02比0.30±0.01，n F＝204.365、6.374、172.800，n P值均<0.05)，差异均有统计学意义。n 结论:DHFZT通过促进肠上皮紧密连接蛋白表达，减轻肠黏膜机械屏障的损伤，达到治疗SAP的目的。“,”Objective:To observe the effect of Dai-Huang-Fu-Zi-Tang (DHFZT) on the intestinal mechanical barrier in the early stage of severe acute pancreatitis (SAP).Methods:Male SD rats (n n=24, aged 7weeks) were randomly divided into sham (SH) group, sham-DHFZT (SH-DHFZT) group, SAP group, DHFZT treatment (SAP-DHFZT) group, 6 rats per group. After laparotomy, the pancreas of rats in the SH group and the SH-DHFZT group was turned several times and then abdomen closed. SAP model was induced in SAP group and SAP-DHFZT group by slow retrograde injection of 4% sodium taurocholate (1 ml/kg) through pancreatic bile duct. After operation, the SH group, SAP group, SH-DHFZT group and SAP-DHFZT group were treated with 2 ml normal saline or DHFZT for retention enema at 12, 24 and 36 h after operation, respectively. Serum amylase, serum calcium, endotoxin, interleukin-1β (IL-1β), and intestinal mucosal diamine oxidase (DAO) concentrations were measured. The expression levels of Claudin-1, Occludin, zonula occludens 1 (ZO-1), and intestinal histopathological scores were compared. Data were analyzed using one-way ANOVA in SPSS 22.0 software.n Results:Serum levels of endotoxin, amylase, DAO and IL-1β in SAP group were significantly higher than those in SH group [endotoxin (132.40±8.00) ng/L vs. (31.70±8.40) ng/L; amylase (1 163.00±71.88) U/L vs. (174.20±8.89) U/L; DAO (23.11±2.98) μg/L vs. (10.76±2.42) μg/L; IL-1β (82.20±7.14) μg/L vs. (25.37±2.38) μg/L,n F=452.162, 1 118.302, 62.099, 342.100, all n P<0.05]. Serum calcium content in SAP group was lower than in SH group [(1.25±0.16) mmol/L vs. (1.99±0.10) mmol/L,n F=92.292, n P<0.05]. Serum endotoxin, amylase, DAO and IL-1β levels in SAP-DHFZT group were lower than those in SAP group [endotoxin (68.80±5.30) ng/L vs. (132.40±8.00) ng/L; amylase (500.70±54.67) U/L vs. (1163.00±71.88) U/L; DAO (13.79±2.93) μg/L vs. (23.11±2.98) μg/L; IL-1β (63.03±7.27) μg/L vs. (82.20±7.14) μg/L,n F=263.544, 322.707, 29.841, 21.235, all n P<0.05], and blood calcium was higher than that in SAP group [(1.72±0.08) mmol/L vs. (1.25±0.16) mmol/L,n F=41.419, n P<0.05]. The structure of pancreatic tissue, lung tissue and ileum were all destroyed after SAP, and the expression of ZO-1, Occludin and Claudin-1 in intestinal epithelium was weakened. After treatment with DHFZT, the damaged structures of pancreas and ileum were repaired, and the expression levels of intestinal epithelial tight junction proteins ZO-1, Occludin and Claudin-1 were higher than those in SAP group (ZO-1 0.80±0.12 vs. 0.09±0.02; Occludin 0.69±0.11 vs. 0.53±0.11; Claudin-1 0.42±0.02 vs. 0.30±0.01,n F=204.365, 6.374, 172.800, n P<0.05).n Conclusion:DHFZT alleviates the damage of intestinal mechanical barrier by promoting the expression of intestinal epithelial tight junction protein.