CAJ | 학술논문

目的建立一种易于构建而非致死性的继发性噬血淋巴组织细胞增生症(HLH)小鼠模型,以便更好地用于HLH的研究.方法以成年野生型C57BL/6小鼠为对象,隔日腹腔注射CpG寡脱氧核苷酸(CpG-ODN) 1826,每日皮下注射IFN-γ诱导产生HLH,观察小鼠给药后的一般状况及检测HLH相关指标.结果 CpG-ODN组小鼠给药后第10天出现HLH样症状,血常规检查显示全血细胞减少,单核细胞比例增加,淋巴细胞及中性粒细胞比例未见明显变化;有肝损伤表现,丙氨酸转氨酶升高为(198.7±54.2)IU/L;白蛋白降低为(217.7±4.3)g/L;纤维蛋白原降低为(17.1±1.9)g/L;甘油三酯升高为(12.1±0.6)g/L;血清铁蛋白升高为(708.4±11.8)pmol/L.与对照组相比,差异均有统计学意义(P＜0.05).肝脏和脾脏明显肿大,肝脏炎症反应明显,以多灶性肝细胞坏死和血管周围炎症为主要表现,脾脏红髓区扩大、有核细胞增生;肝脾组织中活化巨噬细胞显著增多;肝脏、脾脏病理组织切片及骨髓涂片中可见噬血现象.CpG-ODN组小鼠无致死性表现,仅在第1次给药后活动量明显减少.结论 CpG-ODN 1826和IFN-γ联合作用可以诱导野生型C57BL/6小鼠出现类HLH反应,且不会使其出现致死性疾病,可以作为一种研究继发性HLH的模型.
목적 건립일충역우구건이비치사성적계발성서혈림파조직세포증생증(HLH)소서모형,이편경호지용우HLH적연구.방법 이성년야생형C57BL/6소서위대상,격일복강주사CpG과탈양핵감산(CpG-ODN) 1826,매일피하주사IFN-γ유도산생HLH,관찰소서급약후적일반상황급검측HLH상관지표.결과 CpG-ODN조소서급약후제10천출현HLH양증상,혈상규검사현시전혈세포감소,단핵세포비례증가,림파세포급중성립세포비례미견명현변화;유간손상표현,병안산전안매승고위(198.7±54.2)IU/L;백단백강저위(217.7±4.3)g/L;섬유단백원강저위(17.1±1.9)g/L;감유삼지승고위(12.1±0.6)g/L;혈청철단백승고위(708.4±11.8)pmol/L.여대조조상비,차이균유통계학의의(P＜0.05).간장화비장명현종대,간장염증반응명현,이다조성간세포배사화혈관주위염증위주요표현,비장홍수구확대、유핵세포증생;간비조직중활화거서세포현저증다;간장、비장병리조직절편급골수도편중가견서혈현상.CpG-ODN조소서무치사성표현,부재제1차급약후활동량명현감소.결론 CpG-ODN 1826화IFN-γ연합작용가이유도야생형C57BL/6소서출현류HLH반응,차불회사기출현치사성질병,가이작위일충연구계발성HLH적모형.
Objective To establish a hemophagocytic lymphohistiocytosis (HLH)-like mouse model induced by CpG oligodeoxynucleotide (CpG-ODN1826) and interferon (IFN)-γ for further study on therapy.Methods Wild type adult C57BL/6 mice were administered with PBS or CpG-ODN1826(50 μg) by intraperitoneal injection every two day and IFN-γ subcutaneous injection every day.Parameters of HLH were evaluated on day 10.Results As compared to control,HLH-like symptoms in CpG group were characterized with pancytopenia accompanied by increased ratios of monocytes,alanine aminotransferase [(198.7±54.2) IU/L],triglyceride level [(12.1 ±0.6)g/L],and serum ferritin [(708.4± 11.8)pmol/L] ;decreased albumin [(217.7±4.3) g/L],fibrinogen [(17.1 ± 1.9) g/L] (all P＜0.05).Hepatosplenomegaly was obvious in CpG group.The liver in CpG group had multifocal hepatocytes necrosis and perivascular inflammations.Spleen had expanding red pulp and hyperplastic nucleated cells.Furthermore,macrophages in the liver and spleen were largely activated.Hemophagocytosis were observed in liver,spleen and bone marrow smear.The CpG group was alive during experiment,other than significant decreased activity after the first injection of CpG-ODN.Conclusions These data demonstrate that repeated administration of CpG-ODN1826 and IFN-γ could induce HLH-like symptoms without fatal condition in wild type C57B/L mice.This protocol could establish a mild HLH-like mouse model,which could be useful for further study on HLH.