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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 investigate the protective effect of probiotics on the gastrointestinal disorders induced by chemotherapy in children with medulloblastoma and the anti-inflammatory mechanism. Methods From March 2013 to October 2014, 200 children with medulloblastoma undergoing chemotherapy in our department of pediatric hematology and oncology were all diagnosed by CT, MRI and pathology. Tumor was completely resected after diagnosis HIT-2000 / GPOH regimen chemotherapy. There were 106 males and 94 females, aged 2-18 years, with a median age of 7.2 years. There were 88 patients with chemotherapy alone and 112 patients with chemotherapy after radiotherapy. All patients had no history of taking antibiotics and probiotics within 2 weeks. According to age, sex, body weight, body surface area paired into two groups: (1) the experimental group: 1 week before chemotherapy began routine administration of intestinal intestine (Northeast Pharmaceutical Group Shenyang No. 1 Pharmaceutical Co., Ltd., batch number S10950019, , 3 times a day) until the end of chemotherapy; (2) control group: given placebo orally, did not take any probiotics. The incidence of gastrointestinal disorders in children was observed. The changes of ET, TNF-α, IL-1β, IL-6 and CRP levels in children with peripheral blood were detected at 1 day before and 1 day after chemotherapy . Comparison between the two groups using chi-square or t test. Results In this study, about 75% of children had different degrees of gastrointestinal dysfunction. The incidence of gastrointestinal disturbances in the experimental group was significantly decreased after intervention of the whole intestine, with significant difference (χ ~ 2 = 12.553, P <0.05). The incidence of gastrointestinal disorders in children who underwent chemotherapy after radiotherapy increased significantly (83.93%, χ ~ 2 = 10.823, P <0.05) compared with those who received chemotherapy alone. Further study found that there was no significant difference in the serum inflammatory markers between the pre-chemotherapy and control groups (P> 0.05), while the levels of serum ET, CRP, TNF-α, IL-1β and IL- 6 levels were significantly increased (tET = 23.451, tCRP = 33.246, tIL-1β = 27.453, tIL-6 = 29.372, tTNF-α = Serum levels of ET and CRP were significantly higher in children with chemotherapy alone (tET = 4.396, tCRP = 4.216, P <0.05). The levels of serum ET, CRP and inflammatory cytokines TNF-α, IL-1β and IL-6 in children with intestine were significantly lower than those in control group (tET = 7.905, tCRP = 7.670, tIL- 1β = 10.459, tIL-6 = 9.176, tTNF-α = 11.879, P <0.05). The serum levels of ET and CRP and the levels of TNF-α, IL-1β and IL-6 in the experimental group and the control group The same trend. Conclusion Intestine can significantly improve the gastrointestinal function of cytotoxic drugs in children with medulloblastoma damage, maintain the steady state of intestinal flora, inhibit the immune inflammatory reaction. Tumor patients in the course of treatment can be prophylactic use of intestinal rectum to ease gastrointestinal disorders, reduce inflammation and improve the quality of life of children with cancer and chemotherapy tolerance.