鼠李糖乳杆菌通过调节肠道微生物群缓解造血干细胞移植后肝脏移植物抗宿主病

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (9): 1303-1308.

鼠李糖乳杆菌通过调节肠道微生物群缓解造血干细胞移植后肝脏移植物抗宿主病

房婷¹, 李响², 刘洁³, 王皓^4*

中国人民解放军第960医院 1.血液病科; 4.普外科,山东济南 250031;
2.中国人民解放军93381部队医院, 黑龙江五常 150223;
3.常州市第二人民医院血液内科,江苏常州 213000

收稿日期:2020-09-07 修回日期:2021-01-09 出版日期:2021-09-05 发布日期:2021-09-02
通讯作者: *123028856@qq.com
基金资助:
南京医科大学科技发展基金(NMUB201)

Lactobacillus rhamnoides alleviates liver graft-versus-host disease after transplantation of hematopoietic stem cell through regulating intestinal microbiota

FANG Ting¹, LI Xiang², LIU Jie³, WANG Hao^4*

1. Department of Hematology; 4.Department of General Surgery, 960th Hospital of Chinese People's Liberation Army, Jinan 250031;
2. Chinese People's Liberation Army 93381 Army Hospital, Wuchang 150223;
3. Department of Hematology, Changzhou Second People's Hospital, Changzhou 213000, China

Received:2020-09-07 Revised:2021-01-09 Online:2021-09-05 Published:2021-09-02
Contact: *123028856@qq.com

摘要/Abstract

摘要： 目的探讨鼠李糖乳杆菌GG菌株(LGG)对造血干细胞移植(HSCT)后肝脏移植物抗宿主病(GVHD)的影响及机制。方法将小鼠随机分为对照组,GVHD组(通过尾静脉回输供体来源骨髓和脾细胞悬液),及LGG组(造模后LGG灌胃处理,200 μL/只,一周2次,持续5周)。HE染色观察肝脏病理改变;ELISA检测肝功能和血浆细胞因子IL-6、IL-18和TNF-α的水平;PCR检测肠道微生物群的变化。结果相比对照组,GVHD组小鼠生存期缩短,呈现肝功能损伤及病理改变,血浆细胞因子IL-6、IL-18和TNF-α显著升高(P＜0.01),且肠道微生物群多样性下降(P＜0.05)。LGG处理明显减轻了肝脏中GVHD诱发的上述病理改变(P＜0.05)。结论 LGG可以通过补充肠道微生物群的多样性减轻肝脏炎性因子水平,进而缓解小鼠HSCT后肝脏GVHD,提示LGG可能用于治疗GVHD。

关键词: 造血干细胞移植, 肝脏移植物抗宿主病, 肠道微生物群, 炎性因子

Abstract: Objective To investigate the effect and mechanism of Lactobacillus rhamnosus GG strain(LGG) on liver graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Methods Mice were randomly divided into three groups, including control, GVHD (the donor-derived bone marrow and spleen cell suspension were reinfused through the tail vein), and LGG groups (LGG gavage after modeling, 200 μL/mouse, twice a week for 5 weeks). The pathological changes of liver tissues were observed by HE staining, the liver function and the levels of plasma cytokines IL-6, IL-18 and TNF-α were detected by ELISA, and the changes of intestinal microbiota were detected by PCR. Results Compared with mice in the control group, mice in GVHD group showed shorter survival time, obvious liver function damage and pathological changes, increased level of plasma cytokines IL-6, IL-18 and TNF-α (P＜0.01) and decreased intestinal microbiota diversity(P＜0.05). LGG treatment significantly alleviated the pathological changes induced by GVHD in the liver (P＜0.05). Conclusions LGG can reduce the level of inflammatory factors in liver by regulating the intestinal microbiota, thereby alleviate GVHD in mice after HSCT, suggesting that LGG may be useful in the treatment of GVHD.

Key words: hematopoietic stem cell transplantation, liver graft-versus-host disease, intestinal microbiota, inflammatory factor

中图分类号:

R457.7

房婷, 李响, 刘洁, 王皓. 鼠李糖乳杆菌通过调节肠道微生物群缓解造血干细胞移植后肝脏移植物抗宿主病[J]. 基础医学与临床, 2021, 41(9): 1303-1308.

FANG Ting, LI Xiang, LIU Jie, WANG Hao. Lactobacillus rhamnoides alleviates liver graft-versus-host disease after transplantation of hematopoietic stem cell through regulating intestinal microbiota[J]. Basic & Clinical Medicine, 2021, 41(9): 1303-1308.

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