白头翁汤联合PD-1抑制剂对结肠癌小鼠免疫微环境的影响  

Effect of Baitouweng decoction combined with PD-1 inhibitor on immune micro-environment of colon cancer mice

作　　者：塔吉姑丽·吐逊 陈治宇 马琪琪 节阳华[2] TAJIGULI Tuxun;CHEN Zhiyu;MA Qiqi;JIE Yanghua(The Fourth Clinical Medical College of Xinjiang Medical University,Urumqi 830054,China;Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第四临床医学院,新疆乌鲁木齐830054 [2]新疆医科大学附属中医医院,新疆乌鲁木齐830054

出　　处：《陕西中医》2025年第2期170-175,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：新疆维吾尔自治区自然科学基金资助面上项目(2022D01C560);新疆维吾尔自治区“天山英才”医药卫生高层次培养计划项目(TSYC202301B080)。

摘　　要：目的:探讨白头翁汤联合PD-1抑制剂对结肠癌小鼠肿瘤细胞生长的影响,以及中药及免疫联合治疗对结直肠癌小鼠免疫微环境的影响。方法:按照随机数字表法将SPF雌性BALB/c小鼠用皮下移植方法制备结肠癌模型,造模成功的48只小鼠随机分为模型组,PD-1抑制剂组,白头翁汤组,白头翁加PD-1抑制剂组四个实验组,每组各12只。分别给予0.9%氯化钠溶液,PD-1抑制剂,白头翁汤,白头翁汤加PD-1抑制剂治疗。干预21 d后,采用HE染色、活体成像技术、酶联免疫吸附测定法、蛋白印迹法、流式细胞术测定以上四组小鼠肿瘤组织内白介素-2(IL-2)、白介素-6(IL-6)、白介素-17A(IL-17A)、转化生长因子-β1(TGF-β1)、调节性T细胞(Treg)以及PD-1/PD-L1的表达量。结果:白头翁汤+PD-1抑制剂组与模型组比较,Treg细胞浓度显著降低(P<0.05),IL-17A含量明显增高,其血清中IL-2、IL-6含量显著上升,TGF-β1含量显著下调(P<0.05)。与模型组比较,白头翁汤+PD-1抑制剂组小鼠胸腺指数显著增高,PD-1/PD-L1蛋白表达水平显著降低(P<0.05)。白头翁汤组与模型组比较肿瘤组织坏死面积显著增加。白头翁汤组与模型组相比较,荧光强度总指数及平均值均明显降低(P<0.05)。结论:白头翁汤+PD-1抑制剂可有效抑制肿瘤细胞免疫逃逸,增强杀瘤活性,减轻炎症反应,激活抗肿瘤免疫发挥作用。其作用机制可能与下调Treg、TGF-β1浓度,升高血清中IL-2、IL-6及IL-17A等细胞因子,改善炎症微环境及免疫状态,重塑免疫表型,逆转免疫抑制微环境有关。Objective:To investigate the effects of Baitouweng decoction combined with PD-1 inhibitor on tumor cell growth in colorectal cancer mice,and the effects of traditional Chinese medicine combined with chemotherapy-therapy on immune micro environment in colorectal cancer mice.Methods:The colon cancer mouse model of SPF female BALB/c was established by subcutaneous transplantation.48 successful mice were randomly divided into four experimental groups,model group,PD-1 inhibitor group,Baitouweng decoction group,Baitouweng decoction plus PD-1 inhibitor group,with 12 mice in each group.0.9%sodium chloride solution,PD-1 inhibitor,Baitou Weng decoction and Baitouweng decoction plus PD-1 inhibitor were given respectively.After 21 days of intervention,HE staining,in vivo imaging,enzyme-linked immunosorbent assay,Western blotting and flow cytometry were used to determine the expression of interleukin-2(IL-2),interleukin-6(IL-6),interleukin-17A(IL-17A)transforming growth factor-β1(TGF-β1),regulatory T cells(Treg)and PD-1/PD-L1 in the tumor tissues of the above four groups.Results:Compared with the model group,the concentration of Treg cells in Baitouweng decoction+PD-1 inhibitor group decreased significantly,the content of IL-17A increased significantly,the content of IL-2,IL-6 in serum increased significantly,and the content of TGF-β1 decreased significantly(P<0.05).Compared with the model group,the thymus index of Baitouweng decoction+PD-1 inhibitor group was significantly higher and the expression level of PD-1/PD-L1 protein was significantly lower than that of model group.The necrotic area of tumor tissue in Baitouweng decoction group was significantly higher than that in model group.The total index and average index of fluorescence intensity in the Baitouweng decoction group were significantly lower than those in the model group(P<0.05).Conclusion:Baitouweng decoction plus PD-1 inhibitor can effectively inhibit tumor cell immune escape,enhance tumor-killing activity,reduce inflammatory reaction and activate anti-tumor

关 键 词：结直肠癌 白头翁汤 肿瘤免疫微环境 程序性死亡受体1/程序性死亡配体1 白介素 

分 类 号：R735.35[医药卫生—肿瘤]