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髓源抑制细胞对HBV转基因小鼠肝脏炎症损伤抑制作用的研究
  • ISSN号:1674-1358
  • 期刊名称:《中华实验和临床感染病杂志(电子版)》
  • 时间:0
  • 分类:R512.62[医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]北京大学人民医院北京大学肝病研究所丙型肝炎及肝病免疫治疗北京市重点实验室,北京100044, [2]首都医科大学附属北京地坛医院, [3]新发突发传染病研究北京市重点实验室
  • 相关基金:国家自然科学基金重大计划(No.91029741);国家自然科学基金(No.81001072,No.81171550)
中文摘要:

目的:建立HBV抗原特异性细胞毒性T细胞(CTLs)介导的小鼠肝炎模型,探讨肿瘤诱导的髓源抑制性细胞(MDSCs)在免疫介导的HBV转基因小鼠肝损伤中的有效性。方法制备新鲜的HBV转基因小鼠肝脏匀浆,予普通小鼠腹腔注射,1次/周,连续4周,以诱导致敏小鼠(Sensitized-mice)产生HBV抗原特异性CTLs(HBV-specific CTLs,HBV-CTLs)。分离致敏小鼠脾脏来源HBV-CTLs,静脉回输给高复制型HBV转基因小鼠,分别在注射前,注射后1 d、3 d、6 d和9 d经眶后取血测血清ALT/AST水平。分离荷瘤小鼠骨髓来源的MDSCs,静脉注射给HBV-CTLs诱导的肝炎小鼠,并在注射后24 h,经眶后取血测血清ALT/AST水平,肝脏组织经固定、石蜡包埋、HE染色进行组织形态学检测。结果致敏小鼠脾脏来源的HBV-CTLs可诱导HBV转基因小鼠肝组织损伤,血清ALT、AST水平呈升高趋势;且与CTLs注射组小鼠相比,CTLs联合MDSCs注射组小鼠肝脏组织损伤程度减轻,小鼠血清转氨酶水平显著降低[ALT:(254.5±25.50)vs (80.67±11.57),P <0.05;AST:(301.5±40.50)vs(249.0±79.00),P >0.05)]。结论静脉回输肿瘤诱导的MDSCs可有效减轻HBV-CTLs诱导的肝炎小鼠中肝组织损伤。

英文摘要:

Objectives To establish murine hepatitis model in HBV transgenic mice and to investigate the role of Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs) in attenuating liver injury in immune-mediated murine hepatitis model. Methods Repetitive intraperitoneal injection of liver homogenate from HBV transgenic mice into na?ve BALB/c mice (recipient mice) was performed at once a for four weeks. HBV-specific CTLs (HBV-CTLs) were from spleen of recipient mice. Tumor-induced MDSCs were isolated from bone marrow of tumor-bearers and purified by magnetic system. HBV transgenic mice were treated with HBV-CTLs injection (1 × 107/per mouse, i.v.) or co-injection of HBV-CTLs (1 × 107/per mouse, i.v.) and MDSCs (5 × 106/per mouse, i.v.). Serum ALT/AST levels were detected before and 24 hours after cells transfer to evaluate the liver injury. Paraffin-embedded liver tissue was sectioned for HE staining. Results HBV-CTLs injection caused acute liver injury in HBV transgenic mice were observed, characterized by acute increase of serum ALT and/or AST levels. Co-injection of CTLs and MDSCs could effectively attenuate liver injury in hepatitis mouse model (ALT: 254.5 ± 25.50 vs 80.67 ± 11.57, P 0.05). Morphological analysis showed alleviation of liver injury in mice injected with HBV-CTLs and MDSCs. Conclusion These results demonstrate that tumor-induced MDSCs play a role of suppressing immune-mediated hepatitis.

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期刊信息
  • 《中华实验和临床感染病杂志(电子版)》
  • 中国科技核心期刊
  • 主管单位:中华人民共和国卫生和计划生育委员会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京朝阳区京顺东街8号北京地坛医院
  • 邮编:100015
  • 邮箱:editordt@163.com
  • 电话:010-84322058
  • 国际标准刊号:ISSN:1674-1358
  • 国内统一刊号:ISSN:11-9284/R
  • 邮发代号:
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),中国中国科技核心期刊
  • 被引量:4609