摘要
目的初步探讨微生态制剂对髓母细胞瘤患儿化疗所致胃肠功能紊乱的保护作用及抗炎机制。方法 2013年3月至2014年10月在我院儿童血液肿瘤科接受化疗的髓母细胞瘤患儿共200例,所有患儿均经CT、MRI和病理明确诊断,确诊后完全切除肿瘤,均接受HIT-2000/GPOH方案化疗。其中男106例,女94例,年龄2~18岁,中位年龄7.2岁。单纯化疗患儿88例,放疗后继续化疗患儿112例,所有患儿2周内无抗生素及微生态制剂服用史。根据年龄、性别、体重、体表面积配对分为两组：（1）试验组：化疗前1周开始常规给予整肠生口服（东北制药集团沈阳第一制药有限公司,批号S10950019,每次1粒,每日3次）,至化疗结束;（2）对照组：给予安慰剂口服,未服用任何微生态制剂。观察患儿胃肠功能紊乱的发生情况,并于化疗前1天和结束后第1天抽取患儿外周血,测定血清ET、TNF-α、IL-1β、IL-6、CRP等水平的变化。两组间比较采用卡方或t检验。结果本课题中约75%患儿出现不同程度的胃肠功能紊乱,给予整肠生干预后试验组患儿的胃肠紊乱发生率显著下降,差异有统计学意义（χ^2=12.553,P〈0.05）;放疗后继续化疗的患儿胃肠功能紊乱的发生率较单纯接受化疗的患儿显著增加（达83.93%,χ^2=10.823,P〈0.05）。进一步研究发现,化疗前试验组与对照组患儿血清各炎症指标间差异均无统计学意义（P〉0.05）;而化疗后患儿血清ET、CRP、TNF-α、IL-1β、IL-6水平显著升高,差异具有统计学意义（tET=23.451,tCRP=33.246,tIL-1β=27.453,tIL-6=29.372,tTNF-α=16.223,P〈0.05）;其中放疗后继续化疗的患儿血清ET、CRP水平与单纯接受化疗的患儿比较明显增高,差异有统计学意义（tET=4.396,tCRP=4.216,P〈0.05）。给予整肠生制剂干预后患儿血清ET、CRP和炎症因子TNF-α、IL-1β、IL-6水平较对照组显著下降,差异有统计学意义（tET=7.905,tCRP=7.670,tIL-1β=10.459,tIL-6=9.176,tTNF-α=11.879,P〈0.05）,且试验组和对照组患儿血清ET、CRP水平与各炎症因子TNF-α、IL-1β、IL-6水平变化趋势一致。结论整肠生可显著改善细胞毒性药物对髓母细胞瘤患儿的胃肠功能损害,维护肠道菌群稳态,抑制其免疫炎性反应。肿瘤患儿在治疗过程中可预防性服用整肠生缓解胃肠道功能紊乱,减轻炎症反应,提高肿瘤患儿的生存质量和化疗耐受性。
Objective To explore the inhibitory effects of probiotics on chemotherapy induced gastrointestinal reactions and the anti-inflammatory mechanisms in children with medulloblastoma.Methods 200 children with medulloblastoma who met the including criteria were enrolled and divided into the experiment group or control group respectively according to age,gender,body weight and body surface area.The experiment group was given Bacillus licheniformis preparation（ZCS）,one piece t.i.d.,while the control group was give placebo during the chemotherapy.Peripheral blood specimens were collected one day before and one day after the chemotherapy to detect the levels of serum endotoxin（ET）,C-reactive protein（CRP）,tumor necrosis factorα（TNF-α）,interleukin-1（IL-1β）and interleukin-6（IL-6）with enzyme-linked immunosorbent assay（ELISA）.Comparisons between two groups were performed with Chi square test or Student′s t-test.Results Approximately above 75% of the patients suffered different degrees of gastrointestinal symptoms.After taking ZCS,the incidence of gastrointestinal disorders was reduced obviously（χ2=12.553,P〈0.05）.The patients accepting chemotherapy after radiotherapy were more prone to gastrointestinal disorders than those accepting chemotherapy alone.The differences in the levels of ET,CRP,TNF-α,IL-1βand IL-6between the two groups were not significant before chemotherapy（P〈0.05）but after chemotherapy（tET =23.451,tCRP=33.246,tIL-1β=27.453,tIL-6=29.372,tTNF-α=16.223,P〈0.05）.Compared with those accepting chemotherapy after radiotherapy,the levels of ET and CRP of the patients accepting chemotherapy alone increased significantly（tET=4.396,tCRP=4.216,P〈0.05）.After taking ZCS,the levels of ET,CRP,TNF-α,IL-1βand IL-6of the experiment group decreased significantly than the control group（tET=7.905,tCRP=7.670,tIL-1β=10.459,tIL-6=9.176,tTNF-α=11.879,P〈0.05）,and the changes of the levels of TNF-α,IL-1βand IL-6were consistent with those of ET and CRP in both groups.Conclusion Prophylactical administration of Bacillus licheniformis probiotics during chemotherapy for medulloblastoma patients can relieve chemotherapy-related gastrointestinal disorders,modulate intestinal homeostasis,inhibit the inflammatory reactions after chemotherapy,and improve the quality of life of cancer patients.More clinical research should be conducted properly to explore the clinical application of Bacillus licheniformis probiotics among CNST patients.
作者
杜淑旭
任思其
唐泓
龚小军
孙艳玲
李苗
张金
李舒婷
武万水
孙黎明
DU Shuxu REN Siqi TANG Hong GONG Xiaojun SUN Yanling LI Miao ZHANG Jin LI Shuting WU Wanshui SUN Liming(Department of Pediatrics, Shijitan Hospital, the Capital Medical University, Beijing 100038, China)
出处
《中国微生态学杂志》
CAS
CSCD
2016年第11期1264-1268,共5页
Chinese Journal of Microecology
基金
北京市属医院科研培育计划(PX2016058)
关键词
微生态制剂
化学治疗
髓母细胞瘤
胃肠功能紊乱
炎症
儿童
Probiotics
Chemotherapy
Medulloblastoma
Gastrointestinal dysfunction
Inflammation
Pediatric
作者简介
作者简介：杜淑旭（1973-），女，博士，从事儿童肿瘤与微生态学研究，E—mail：dushuxu200811@126．com
通信作者：武万水（1968-），男，硕士，从事儿童肿瘤学研究，E-mail：1wxi@sina．com
