摘要
目的研究供体骨髓来源的白细胞介素12p35（IL-12p35）基因沉默的树突状细胞（IL-12 p35 silenced DC）联合大鼠CD40L单克隆抗体（CD40LmAb）对大鼠小肠移植免疫耐受的诱导。方法实验动物随机分为3组，每组8对，分别于手术前7天进行不同预处理后进行小肠移植。A组：受体注射生理盐水；B组：受体注射供体IL-12 p35 silenced DC，C组：受体静脉注射供体IL-12 p35 silenced DC，同时腹腔注射CD40L mAb。观察受体存活时间，移植小肠采用病理学检察及细胞凋亡检测，受体血清检测IL-2、干扰素（INF）-γ水平。结果C组受体动物存活时间为（23．3±6．0）d，显著长于A、B两组[（6．5±1．5）d，（15．1±4．9）d]；C组移植小肠炎性细胞浸润、黏膜结构破坏程度和肠黏膜细胞的凋亡数目明显低于A、B组[（9．5±5．6）比（23．8±6．2）、（18．7±6．3），（P〈0．01）]；C组受体大鼠血清IL-2浓度为（185．8±18．2）ng／L，显著低于A、B两组[（294．1±15．6）ng／L、（225．8±14．5）ng／L，（P〈0．01、P〈0．05）]；C组受体大鼠血清INF-γ浓度为（75．6±8．6）ng／L，显著低于A、B两组[（110．5±12．4）ng／L、（89．1±9．2）ng／L，（P〈0．01、P〈0．05）]。结论术前输注供体来源的IL-12 p35 silenced DC联合CD40L mAb，可在一定程度上抑制小肠移植的排斥反应，诱导受体产生免疫耐受。
Objective To investigate the combined effects of IL-12 p35 silenced dendritic cells （DCs） with CD40L monoclonal antibody （mAb） on donor-specific tolerance in rats undergoing intestinal transplantation. Methods DCs were collected from bone marrow progenitor cells of rats cultured with GM- CSF and IL-4 in vitro. The IL-12p35 siRNA was chemically synthesized and transfected into DCs. Seven days before transplantation of small intestinal from Wistar donors,IL-12 p35 silenced DCs were infused intravenously into SD recipient rats with injection of anti-CD40L mAb （group C） or without injection of anti- CD40L mAb （group B ）. The rats in control group （group A） were infused with normal saline before transplantation. Small bowel transplantation was performed and the survival time of recipients was observed. Histological examination was done, apoptotic death of infiltrating cells in allografts was analyzed and serum IL- 2 and INF-γ levels were assayed by ELISA. Results The survival time of recipients in group C was （23.3 ± 6.0） days, which was significantly longer than that in groups A and B [ （6.5 ± 1.5） days, （ 15.1 ± 4.9 ） days respectively, P 〈 0.01 ]. The number of apoptosis positive cells in the intestinal mucosa in group C was much less than in groups A and B [ （9.5 ± 5.6 ） vs （ 23.8 ± 6.2） , （ 18.7 ± 6.3 ） respectively,P 〈0.01 ） ], The concentration of serum IL-2 in group C was lower than that in groups A and B [ （185.8 ± 18.2） ng/L vs （294.1 ± 15.6）, （225.8 ± 14.5） ng/L respectively,P〈0.01,P〈0.05） ]. The concentration of serum INF-γ in group C was much lower than that in groups A and B E （75.6 ±8.6） ng/L vs （ 110.5 ± 12.4） and （89.1 ±9.2） ng/L respectively,P 〈0.01 ,P〈0.05） ]. Conclusion The treatment with IL-12 p35 silenced DCs with anti-CD40L mAb can induce immune tolerance and prolong intestinal allografts survival after transplantation.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2007年第3期310-312,共3页
Chinese Journal of Experimental Surgery
关键词
小肠移植
树突状细胞
RNA干涉
Intestinal transplantation
Dendritic cell
RNA interference
