1.上海中医药大学附属普陀医院中医肿瘤科(上海 200062)
汪舒云,女,硕士研究生,主要从事中医药防治恶性肿瘤基础研究工作
邓皖利,教授,主任医师,博士研究生导师; E-mail:dwl0707@163.com
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汪舒云,谢曼丽,孙可向,等.参苓白术散对大肠癌移植瘤模型小鼠化学疗法后肠道黏膜屏障的影响[J].上海中医药杂志,2023,57(4):57-64.
WANG Shuyun,XIE Manli,SUN Kexiang,et al.Effect of Shenling Baizhu Powder on intestinal mucosal barrier in mice with xenograft model of colorectal cancer after chemotherapy[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(4):57-64.
汪舒云,谢曼丽,孙可向,等.参苓白术散对大肠癌移植瘤模型小鼠化学疗法后肠道黏膜屏障的影响[J].上海中医药杂志,2023,57(4):57-64. DOI: 10.16305/j.1007-1334.2023.2206070.
WANG Shuyun,XIE Manli,SUN Kexiang,et al.Effect of Shenling Baizhu Powder on intestinal mucosal barrier in mice with xenograft model of colorectal cancer after chemotherapy[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(4):57-64. DOI: 10.16305/j.1007-1334.2023.2206070.
目的,2,观察参苓白术散对大肠癌移植瘤模型小鼠化学疗法(简称“化疗”)后肠道黏膜屏障的作用效果。,方法,2,将32只SPF级BALB/c小鼠皮下接种CT26肠癌细胞,成瘤后随机分为模型组、奥沙利铂组、参苓白术散组、参苓白术散联合奥沙利铂组,每组8只。模型组予蒸馏水灌胃(0.2 mL/次,1次/d),奥沙利铂组予奥沙利铂5 mg/kg腹腔注射(0.2 mL/次,每3天1次),参苓白术散组15.6 g/kg灌胃(0.2 mL/次,1次/d),参苓白术散联合奥沙利铂组予参苓白术散15.6 g/kg灌胃(0.2 mL/次,1次/d)联合奥沙利铂5 mg/kg腹腔注射(0.2 mL/次,每3天1次),共治疗18 d。治疗结束后每组选取8只小鼠采集血清,以酶联免疫吸附试验(ELISA)法检测血清中二胺氧化酶(DAO)、D-乳酸(D-LA)、白介素-17(IL-17)以及肠道黏膜中肠碱性磷酸酶(IAP)、肠黏膜分泌型免疫球蛋白A(sIgA);剥取小鼠瘤体、脾脏并称重,通过苏木素-伊红(HE)染色法和免疫组织化学(IHC)染色法在组织形态学上分析参苓白术散对小鼠肠道黏膜的影响,并通过流式细胞术检测肿瘤组织中免疫微环境的变化情况。,结果,2,与模型组比较,参苓白术散组、奥沙利铂组以及参苓白术散联合奥沙利铂组均能抑制肿瘤的生长,其中参苓白术散联合奥沙利铂能显著抑制肿瘤的生长(,P,<,0.05);奥沙利铂单独治疗能显著降低肠IAP的表达(,P,<,0.05),同时可以显著升高D-LA(,P,<,0.05)和DAO的表达水平(,P,<,0.05)。HE染色结果表明,参苓白术散可以显著修复化疗之后结肠绒毛的组织学排列,并且减少炎症反应发生。IHC染色结果表明,参苓白术散能显著提高化疗后小鼠结肠紧密连接蛋白闭合蛋白(claudin)、咬合蛋白(occludin)和闭锁小带蛋白-1(ZO-1)的表达水平。和奥沙利铂相比,参苓白术散联合奥沙利铂能缓解肠道黏膜的屏障损伤,一定程度修复化疗引起的肠道黏膜屏障损伤。另一方面,参苓白术散能增加肿瘤微环境中CD8,+,T细胞的浸润。,结论,2,参苓白术散能够保护化疗后肠黏膜屏障,改善肿瘤免疫微环境,从而抑制小鼠皮下移植瘤的生长。
Objective,2,To observe the effect of Shenling Baizhu Powder (SLBZ) on intestinal mucosal barrier in mice with xenograft model of colorectal cancer after chemotherapy.,Methods,2,Thirty-two SPF grade BALB/c mice were subcutaneously inoculated with CT26 colorectal carcinoma cells, and after tumor formation they were randomly divided into four groups (,n,=8 each): model group, oxaliplatin group, SLBZ group, and SLBZ plus oxaliplatin group. Mice in the model group were given distilled water by gavage (0.2 mL, once daily), mice in the oxaliplatin group were treated with intraperitoneal injection of 5 mg/kg oxaliplatin (0.2 mL, once every 3 days), mice in the SLBZ group were treated with 15.6 g/kg SLBZ by gavage (0.2 mL, once daily), and mice in the SLBZ plus oxaliplatin group were treated with 15.6 g/kg SLBZ by gavage (0.2 mL, once daily) and intraperitoneal injection of 5 mg/kg oxaliplatin (0.2 mL, once every 3 days). The treatment lasted for 18 days. At the end of treatment,8 mice in each group were selected for serum collection, and the enzyme-linked immunosorbent assay (ELISA) was used to detect serum diamine oxidase (DAO), D-lactic acid (D-LA), interleukin-17 (IL-17), intestinal alkaline phosphatase (IAP) and intestinal mucosal secretory immunoglobulin A (sIgA). The tumors and spleens of the mice were excised and weighed. Hematoxylin and Eosin (HE) staining and Immunohistochemistry (IHC) staining were used to analyze the effect of SLBZ on intestinal mucosa of mice in histomorphology, and flow cytometry was used to detect the changes of immune microenvironment in tumor tissues.,Results,2,Compared with the tumor growth condition in the model group, the tumor growth was inhibited in SLBZ group and oxaliplatin group, and significantly inhibited in SLBZ plus oxaliplatin group (,P,<,0.05). Oxaliplatin treatment alone significantly decreased the expression of IAP (,P,<,0.05), and significantly increased the expression of D-LA (,P,<,0.05) and DAO (,P,<,0.05). The results of HE staining showed that SLBZ could significantly repair the histological arrangement of colonic villi after chemotherapy and reduce the occurrence of inflammatory reactions. The results of IHC staining showed that SLBZ could significantly increase the expression of colonic tight junction proteins (claudin), occludin and zonula occludens-1 (ZO-1) in colon of mice after chemotherapy. Compared with the effect of oxaliplatin treatment alone, SLBZ plus oxaliplatin could alleviate the intestinal mucosa barrier damage, and repair the chemotherapy-induced intestinal mucosal barrier damage to a certain extent. Meanwhile, SLBZ could increase the CD8,+, T cell infiltration in the tumor microenvironment.,Conclusion,2,SLBZ can protect the intestinal mucosal barrier after chemotherapy and improve the tumor immune microenvironment, thereby inhibiting the growth of subcutaneously xenograft tumors in mice.
大肠癌经典名方肠道黏膜屏障肿瘤微环境化学疗法模型小鼠中药研究
colorectal cancerChinese classic formulasintestinal mucosal barriertumor microenvironmentchemotherapymouse modeltraditional Chinese herbal medicine research
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