组蛋白乙酰基转移酶与组蛋白去乙酰基酶在哮喘发病中的作用研究

Roles of histone acetyltransferase and histone deacetylase in the pathogenesis of bronchial asthma

摘要:

目的 探讨哮喘病程中各种细胞因子及组蛋白乙酰基转移酶(HAT)和组蛋白去乙酰基酶(HDAC)在哮喘发病中的作用。方法 将32 只BALB/c 小鼠随机分为对照组、哮喘组、激素治疗组和HDAC 抑制剂TSA治疗组, 每组8 只。哮喘小鼠模型采用卵清蛋白腹腔注射致敏及雾化吸入法制作, 对照组采用等量生理盐水行替代注射和雾化吸入, 激素治疗组和TSA 治疗组小鼠在每次激发前30 min 分别予地塞米松1.0 mg/kg(0.2 mL)和TSA 1.0 mg/kg(0.2 mL)腹腔注射。末次激发24 h 后取外周血, 采用酶联免疫吸附试验(ELISA)测定各组血清中细胞因子IL-4、IL-8 和IFN-γ 水平, 酶联免疫荧光法测定各组外周血单个核细胞中HAT 及HDAC 活性。结果 哮喘组血清中IL-4 及IL-8 水平较对照组、激素治疗组和TSA 治疗组升高(P<0.05), IL-4 及IL-8 水平在对照组、激素治疗组和TSA 治疗组间比较差异无统计学意义(P>0.05)。哮喘组HDAC 活性较对照组、激素治疗组和TSA 治疗组均降低, HAT 活性较激素治疗组明显升高(P<0.05);HDAC 和HAT 活性在对照组、激素治疗组和TSA 治疗组间比较差异无统计学意义(P>0.05)。结论 哮喘发病与HDAC 活性下降有关, HDAC活性下降可能引起炎症因子分泌增多从而诱发哮喘。

Abstract:

Objective To evaluate the roles of various cytokines, histone acetyltransferase (HAT) and histone deacetylase (HDAC) in the pathogenesis of bronchial asthma. Methods BALB/C mice were randomly assigned to control, untreated asthma, hormone treatment and TSA treatment groups. Bronchial asthma was induced by intraperitoneal injections and atomization inhalation of ovalbumin (OVA) in the asthma, hormone treatment and trichostatin (TSA) treatment groups. The mice in the hormone treatment and TSA treatment groups were administered with dexamethasone 1.0 mg/kg and TSA 1.0 mg/kg respectively by an intraperitoneal injection 30 minutes before challenge of asthma. At 24 hours after the last challenge, IL-4, IL-8 and IFN- levels in serum were measured using ELISA, and activities of HAT and HDAC in peripheral blood mononuclear cells (PBMC) were determined by the enzyme linked immunofluorescence assay. Results The serum levels of IL-4 and IL-8 in the untreated asthma group were higher than in the control, hormone treatment and TSA treatment groups (P<0.05). There was no difference in the serum levels of IL-4 and IL-8 among the control, hormone treatment and TSA treatment groups (P>0.05). The activity of HDAC in the untreated asthma group was lower than in the control, hormone treatment and TSA treatment groups (P<0.05). Hormone treatment significantly decreased the activity of HAT compared with the untreated asthma group (P<0.05). There was no difference in the activities of HAT and HDAC among the control, hormone treatment and TSA treatment groups (P>0.05). Conclusions The decreased activity of HDAC leads to an increased secretion of inflammatory factors and thus induces asthma.