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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 investigate the mechanism of the development of immune tolerance in liver transplantation by observing the changes of histone deacetylase 11 (HDAC11) and IL-10 expression in three rat models of liver transplantation. Methods Thirty Lewis rats and 30 BN rats were randomly divided into two groups: Lewis-BN, Lewis-BN, BN-lewis, , Each group of 10. The intervention group received intramuscular injection of 1 mg / kg of tacrolimus (FK506) 1 to 7 days after operation. The recipients were sacrificed at 7 days after operation. The degree of graft rejection was evaluated by Banff score. The expression of HDAC11 was observed by immunofluorescence histochemistry. The expression of HDAC11 mRNA and protein in liver tissue was detected by real-time fluorescence quantitative PCR and Western blot. The levels of IL-10 and IFN-γ in serum were detected by enzyme-linked immunosorbent assay Content. Results At 7 days after operation, the rejection group was a severe acute rejection. The Banff score was grade Ⅲ, the intervention group was grade Ⅱ, and the tolerated group was grade 0 ~ I. The level of HDAC11 mRNA and protein expression in rejection group was significantly higher than that in intervention group and tolerated group (P <0.05), and the expression level of HDAC11 in tolerated group was the lowest (P <0.05). The expression of IL-10 in the rejection group was significantly lower than that in the intervention group and the tolerated group (P <0.05), while the levels of IFN-γ in the rejection group were significantly higher than those in the intervention group and the tolerated group (P <0.05). Conclusion HDAC11 can promote or inhibit the formation of immune tolerance of liver transplantation through the regulation of IL-10.