摘要
目的通过观察组蛋白去乙酰化酶11（histone deacetylase 11,HDAC11）及IL-10表达水平在3种大鼠肝移植模型中的变化,探讨肝移植免疫耐受形成的相关机制。方法纯系Lewis和BN大鼠各30只,建立肝移植排斥模型后将受体分为排斥组（Lewis-BN）、免疫抑制剂干预组（Lewis-BN）、耐受组（BN-lewis）,每组10只。干预组于术后1~7 d以1 mg/kg肌肉注射他克莫司（FK506）;分别于术后7 d处死受体。移植物排斥反应程度采用Banff评分标准;免疫荧光组织化学观察HDAC11表达情况;实时荧光定量PCR及Western blot测定肝组织HDAC11 mRNA和蛋白表达水平;酶联免疫吸附法检测血清IL-10及IFN-γ的含量。结果术后7 d,排斥组为严重的急性排斥反应,Banff评分Ⅲ级,干预组为Ⅱ级,耐受组为0~I级。排斥组HDAC11 mRNA及蛋白表达的水平明显高于干预组和耐受组（P〈0.05）,耐受组表达量最低,与干预组有统计学差异（P〈0.05）。排斥组IL-10表达明显低于干预组和耐受组（P〈0.05）;而IFN-γ含量排斥组明显高于干预组和耐受组（P〈0.05）。结论 HDAC11通过对IL-10的调控促进或抑制肝移植免疫耐受的形成。
Objective To observe the changes of histone deacetylase 11（HDAC11） and IL-10 in the 3 rat liver transplantation models,and to explore the related mechanism of the formation of immune tolerance.Methods Thirty pure Lewis and thirty BN rats were used to establish liver transplantation,including 20 pairs of Lewis to BN and 10 pairs of BN to lewis.The recipients were divided into 3 groups： rejection group（Lewis to BN,n=10）,immunosuppressant intervention group（Lewis to BN,n=10） and tolerance group（BN to Lewis,n=10）.The recipients of immunosuppressant intervention group were treated with FK506 at a dose of 1 mg/kg per day by intramuscular injection from 1 to 7 d postoperatively.Rats were killed at the 7th day after transplantation.The extent of acute rejection was assayed by pathological examination.The distribution of HDAC11 was observed by immunofluorescent staining.The expressions of HDAC11 mRNA and protein levels were detected by real-time PCR and Western blot analysis.The levels of serum IL-10 and IFN-γ were measured by ELISA.Results The graft Banff scale on the 7th day after transplantation was higher in rejection group than that in other 2 groups（rejection group,Ⅲ;immunosuppressant intervention group,Ⅱ;tolerance group,0 to I）.The expression of HDAC11 mRNA and protein were significantly higher in rejection group than the other 2 groups（P0.05）.Those of the tolerance group were also lower than those of immunosuppressant intervention group（P0.05）.The IL-10 levels were significantly lower in rejection group than the other 2 groups（P0.05）.But the level of IFN-γ were the highest in rejection group than the other 2 groups（P0.05）.Conclusion It is partly via HDAC11 regulation to IL-10 that promoting or inhibiting the formation of immune tolerance of liver tansplantation.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2011年第4期342-344,共3页
Journal of Third Military Medical University
基金
国家自然科学基金(30972888,30801126)~~
