目的 探讨柴黄清胰活血颗粒调节重症急性胰腺炎 （severe acute pancreatitis，SAP） 模型大鼠肠道微生态变化和治疗重症急性胰腺炎的潜在机制。方法 将 48 只大鼠随机分为假手术组、模型组、柴黄清胰活血颗粒组，每组 16 只；各组再随机分为 12 h 亚组和 24 h 亚组。以肠壁穿刺逆行胰胆管注射 5% 牛磺胆酸钠复制重症急性胰腺炎大鼠模型。假手术组、模型组予以生理盐水灌胃，柴黄清胰活血颗粒组予以 1.2 g•kg-1柴黄清胰活血颗粒溶液灌胃，每间隔 6 h 灌胃 1 次。术后 12 h、24 h，每组各取 8 只大鼠采集腹主动脉血、胰腺及回肠组织备测。观察大鼠腹腔内腹水、胰腺及回肠组织情况；生化法检测血清淀粉酶 （amylase，AMY） 、脂肪酶（lipase，LPS） ；HE 染色观察胰腺及回肠组织病理变化；Western Blot 法检测回肠组织中 Claudin-1 蛋白；16S rDNA 高通量测序检测回盲部内容物肠道菌群变化情况。结果 与相应时点的假手术组比较，模型组大鼠胰腺广泛水肿坏死，血清淀粉酶、脂肪酶明显升高，胰腺组织、回肠组织病理评分升高，回肠组织 Claudin-1 蛋白表达量明显下降 （均 P＜0.05） ；微生物群落的丰度差异性变大，群落组成的均匀度变低，菌群的丰富度无明显变化 （P＞0.05） 而多样性减少 （P＜0.05） ，变形菌门为肠道优势菌，颤螺菌属、瘤胃球菌、双歧杆菌属及拟杆菌S24-7 等菌相对丰度降低，志贺菌、Allobaculum 菌等相对丰度增加；微生物群落的丰度差异性变小，群落组成的均匀度变高，菌群丰富度无明显变化 （P＞0.05） ，而多样性增加 （P＜0.05） ，以厚壁菌门、拟杆菌门为肠道优势菌，颤螺菌属、瘤胃球菌、双歧杆菌、拟杆菌 S24-7 等菌相对丰度增加，志贺菌、Allobaculum 菌等相对丰度降低。经柴黄清胰活血颗粒干预后，回肠组织病理损伤改善，肠黏膜屏障 Claudin-1 蛋白表达量均较模型组增加 （P＜0.05） ；微生物群落的丰度差异性变小，群落组成的均匀度变高，较模型组部分有益菌增多，致病菌减少。结论 柴黄清胰活血颗粒能减轻重症急性胰腺炎大鼠胰腺炎症损伤，其治疗作用可能与调节肠道微生态，改善肠黏膜屏障功能有关。

Objective To explore the regulation of Chaihuang Qingyi Huoxue Granule on intestinal microecological changes in rats with severe acute pancreatitis （SAP） and the potential mechanism for its treatment of SAP. Methods Forty-eight rats were randomly divided into sham operation group （SHAM），SAP model group （SAP），and Chaihuang Qingyi Huoxue Granule （CH） group，with 16 rats in each group. Each group was further divided into 12 h and 24 h subgroups. The SAP model was induced by retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct through duodenal wall. The SHAM and SAP groups received normal saline by gavage，while the CH group received 1.2 g•kg-1 Chaihuang Qingyi Huoxue Granule solution by gavage every six hours. At 12 h and 24 h after operation，eight rats from each group were sacrificed to collect abdominal aortic blood，pancreatic and ileal tissues for analysis. Ascites，pancreatic and ileal tissues were observed. Serum amylase（AMY） and lipase（LPS） levels were measured biochemically. Pathological changes in pancreatic and ileal tissues were investigated by HE staining. Claudin-1 protein expression in ileal tissue was detected by Western Blot. Changes in the intestinal flora of ileocecal contents were analyzed by 16S rDNA high-throughput sequencing. Results Compared to the SHAM group at the same time points，the SAP group exhibited extensive pancreatic edema and necrosis. Serum AMY and LPS levels，pancreatic and ileal histopathological scores increased，and Claudin-1 protein expression in ileal tissue markedly decreased （all P＜0.05）. The differences in abundance of microbial community increased，while the evenness of community composition reduced. The microbial richness showed no significant change （P＞0.05），but the microbial diversity decreased（P＜0.05）. Proteobacteria were dominant intestinal bacteria. Relative abundances of Oscillospira，Ruminococcus，Bifidobacterium，and Bacteroides S24-7 decreased，whereas relative abundances of Shigella and Allobaculum increased. The differences in abundance of microbial community reduced，and the evenness of community composition increased. The microbial richness showed no significant change（P＞0.05），but the microbial diversity increased （P＜0.05）. Firmicutes and Bacteroidetes were the dominant intestinal bacteria. Relative abundances of Oscillospira，Ruminococcus，Bifidobacterium，and Bacteroides S24-7 increased，whereas relative abundances of Shigella and Allobaculum decreased. After the intervention of CH，pathological damage in ileal tissue was improved. The expression of Claudin-1 protein in the intestinal mucosal barrier increased compared to the model group（P＜0.05）. The differences in abundance of microbial community reduced，and the evenness of community composition increased. CH group showed an increase in some beneficial bacteria and decrease in pathogenic bacteria compared to model group. Conclusion Chaihuang Qingyi Huoxue Granule may reduce pancreas injury in rats with SAP，which may be involved in modulating the intestinal microecology and improving intestinal mucosal barrier function.

R285.5

四川省科技计划项目 （2019YFS0163）；西南医大中医院项目 （[2019]119号）；西南医科大学项目 （2023QN080）。