在Lewis小鼠中，PD-1抑制剂与含铂双药化疗联合使用导致结肠炎，并探究其机制。
Colitis induced by PD-1 inhibitor combined with platinum-containing dual drug chemotherapy in Lewis mice and its mechanism.
发表日期：2023 Aug
作者：
Chunhai Li, Lixin Wang, Daqian Sun, Tianxiao Yao, Xiuying Xian, Yufeng Cheng
来源：
Protein & Cell
摘要：
探讨PD-1抑制剂联合铂类双药化疗在Lewis小鼠中发生溃疡性结肠炎的发生和可能机制。建立C57BL/6小鼠的Lewis肺癌模型，将其随机分为治疗组（C组，PD-1抑制剂+卡铂+培美曲塞）和模型组（B组，生理盐水），并设置了对照组（A组，生理盐水）。观察每组动物的肿瘤质量、肿瘤体积、疾病活动指数（DAI）、结肠组织病理变化、血清白细胞介素（IL）-10、干扰素（IFN）-γ、claudin-1和occludin mRNA在结肠中的表达。
与A组相比，B组小鼠的肿瘤质量降低（P < 0.001），血清IL-10含量增加（P < 0.01），血清IFN-γ含量降低（P < 0.01）。与B组相比，C组移植肿瘤体积减少（P < 0.05），D4时和D7时DAI评分增加（P < 0.001），结肠组织病理分析显示发生了溃疡性结肠炎，血清IL-10含量减少（P < 0.05），IFN-γ含量增加（P < 0.05），claudin-1（P < 0.05）和occludin（P < 0.05）mRNA的表达降低。
该治疗可以抑制移植肿瘤的生长，但会导致Lewis小鼠发生溃疡性结肠炎。给药后，肠道屏障功能损伤导致结肠中炎症因子的表达失衡，从而引发溃疡性结肠炎。
To explore the occurrence and possible mechanism of colitis in Lewis mice treated with PD-1 inhibitor combined with platinum-containing dual drug chemotherapy.A Lewis lung cancer model of C57BL/6 mice was established, randomly divided into the treatment group (group C, PD-1 inhibitor + Carboplatin (CARB) + Pemetrexed (PEM)) and model group (group B, normal saline), and a control group (group A, normal saline) was set up. Observe the changes in tumor-free weight, tumor volume, disease activity index (DAI), colon histopathology, identify serum interleukin (IL)-10, interferon (IFN)-γ, the expression of claudin-1, and occludin mRNA in the colon in each animals.Compared with group A, the tumor-free weight of mice in B decreased (P < 0.001), the content of IL-10 in serum increased (P < 0.01), the content of IFN-γ in serum decreased (P < 0.01). Compared with group B, the transplanted tumor volume in C was reduced (P < 0.05), DAI scores of D4 (P < 0.001), and D7 (P < 0.001) were increased, colonic histopathology analysis showed that colitis occurred, serum IL-10 content was decreased (P < 0.05), IFN-γ content was increased (P < 0.05), and the mRNA expression of claudin-1 (P < 0.05) and occludin (P < 0.05) was reduced.This treatment can inhibit the growth of transplanted tumors but will cause colitis in Lewis mice. The impairment of intestinal barrier function following administration cause an imbalance in the expression of pro-inflammatory and anti-inflammatory factors in the colon, thus causing colitis.