静注人免疫球蛋白对奥沙利铂诱导小鼠脾脏/肠道损伤的救治作用  

Therapeutic effects of IVIG on oxaliplatin-induced spleen and intestinal injuries in mice

作　　者：覃余燕 袁欣 张巍 王宗奎 李长清 QIN Yuyan;YUANXin;ZHANG Wei;WANG Zongkui;LI Changqing(Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College,Chengdu 610052,China;International Science and Technology Cooperation Base of Sichuan Blood Safety and Blood Substitute)

机构地区：[1]中国医学科学北京协和医学院输血研究所,四川成都610052 [2]四川省血液安全与血液替代国际科技合作基地

出　　处：《中国输血杂志》2023年第4期279-284,共6页Chinese Journal of Blood Transfusion

基　　金：中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-042);四川省自然科学基金面上项目(2023NSFSC0714)。

摘　　要：目的探讨静注人免疫球蛋白(intravenous immunoglobuin,IVIG)对奥沙利铂诱导的化疗损伤小鼠的救治效果。方法将6~8周龄的野生型雄性BALB/c小鼠51只,随机均分为:1)空白对照组;2)化疗组(腹腔注射奥沙利铂);3)干预组(注射奥沙利铂后给予IVIG)。通过外周血细胞计数、解剖学、HE(苏木精-伊红)染色、PAS(过碘酸雪夫)染色及Luminex等方法研究各组小鼠的外周血细胞组成、脾指数、脾脏和肠道的病理学特征、结肠炎症因子水平等,分析IVIG对奥沙利铂诱导的化疗损伤的救治效果。结果与空白对照组相比,化疗组小鼠外周血中的白细胞数量(109/L)(2.45±0.51 vs 0.75±0.27,P<0.0001)和血小板数量(109/L)(1249.00±100.04 vs 347.55±110.33,P<0.0001)显著减少,淋巴细胞比例(75.37%±7.30%vs 62.57%±12.09%,P<0.001)明显下降,脾指数显著降低(P<0.0001),结肠中的杯状细胞减少(P<0.05)、促炎因子TNF-α和IFN-γ(P<0.01)升高、抗炎因子IL-10和IL-13(P<0.05)降低。与化疗组相比,IVIG干预则明显增加了小鼠外周血中的白细胞数量(109/L)(0.75±0.27 vs 1.11±0.30,P<0.05)和血小板数量(109/L)(347.55±110.33 vs 698.49±182.86,P<0.0001),提高了淋巴细胞比例(62.57%±12.09%vs 71.40%±9.08%,P<0.05),脾指数也明显升高(P<0.0001),增加了小鼠结肠中杯状细胞的数量(P<0.01),降低促炎因子TNF-α的水平(P<0.05)、升高抗炎因子IL-10和IL-13(P<0.05)的水平。结论在奥沙利铂诱导的化疗损伤小鼠中,IVIG能够减轻小鼠的造血系统、脾脏和肠道损伤,提示IVIG可用于改善奥沙利铂在肿瘤患者化疗中引起的机体损伤。Objective To investigate the effects of intravenous immunoglobulin(IVIG)on oxaliplatin-induced chemotherapy injury in mice.Methods Fifty-one wild-type male BALB/c mice aged 6-8 weeks were randomly divided into three groups:1)the control group;2)the chemotherapy injury group:the mice were injected with oxaliplatin;3)the treatment group:mice were treated with IVIG after oxaliplatin injection.The effect of IVIG on oxaliplatin-induced chemotherapy injury was evaluated by comparing the differences in the cell composition of peripheral blood,splenic index,pathological features of spleen and colon and colon inflammatory cytokines,which were detected by peripheral blood cell counts,anatomy,hematoxylin-eosin staining,periodic acid-schiff staining and Luminex,respectively.Results Compared with the control group,the counts of white blood cell(10^(9)/L,2.45±0.51 vs 0.75±0.27,P<0.0001)and platelet(10^(9)/L,1249.00±100.04 vs 347.55±110.33,P<0.0001)and the proportion of lymphocytes(75.37%±7.30%vs 62.57%±12.09%,P<0.001)in peripheral blood descend significantly in the chemotherapy injury group.The splenic index remarkably declined(P<0.0001)and the number of goblet cells was also decreased(P<0.05)in chemotherapy-injured mice.Furthermore,the proinflammatory factors TNF-αand IFN-γ increased(P<0.01)and the anti-inflammatory factors IL-10 and IL-13 decreased(P<0.05)in chemotherapy-injured mice.Compared with the chemotherapy injury group,IVIG treatment greatly increased the numbers of white blood cell(10^(9)/L,0.75±0.27 vs 1.11±0.30,P<0.05)and platelet(10~9/L,347.55±110.33 vs 698.49±182.86,P<0.0001)in peripheral blood of mice,and raised the proportion of lymphocytes(62.57%±12.09%vs 71.40%±9.08%,P<0.05).In addition,IVIG not only increased the spleen index of mice(P<0.0001),the number of goblet cells and the levels of IL-10 and IL-13 in the colon of mice(P<0.05),but also decreased the colonic proinflammatory factor TNF-α levels(P<0.05).Conclusion IVIG repaired the damages of hematopoietic system,spleen and intestinal tract

关 键 词：静注人免疫球蛋白 奥沙利铂 化疗损伤 炎症 

分 类 号：R457.14[医药卫生—治疗学] Q954348[医药卫生—临床医学]