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目的 探讨热休克蛋白 90 (HSP90 )与糖皮质激素受体 (GR)比例失调对T淋巴细胞凋亡的作用 ,同时观察地塞米松 (Dex)对HSP90和GRmRNA表达的影响。方法 选择 10例哮喘患者和 7例正常对照 ,利用格尔得霉素 (GA)特异性阻断HSP90的作用 ,造成功能性HSP90与GR比例降低 ,用碘化丙啶 (PI)染色流式细胞仪计数凋亡细胞的方法 ,观察用Dex和GA处理的T细胞凋亡情况 ;用逆转录聚合酶链反应 (RT PCR)的方法观察Dex和GA处理对哮喘T淋巴细胞HSP90和GRmRNA表达的影响。结果 Dex可明显诱导哮喘T淋巴细胞的凋亡 (33 8%± 3 2 %比 2 3 2 %± 1 5 % ,P <0 0 1) ,GA对T淋巴细胞的凋亡无明显影响 ,却可阻断Dex诱导T淋巴细胞凋亡的作用 (2 4 5 %±6 0 %比 33 8%± 3 2 % ,P <0 0 1) ;Dex对正常人T淋巴细胞的凋亡有诱导作用 ,但其程度较弱(2 5 9%± 3 5 %比 2 3 1%± 1 5 % ,P <0 0 5 )。Dex可抑制哮喘患者T淋巴细胞HSP90和GR的表达(分别为 1 2 3± 0 16比 1 6 8± 0 38和 0 42± 0 0 6比 0 5 4± 0 0 7,P均 <0 0 5 ) ,GA对Dex的这一作用有阻断作用 ,但GA本身对HSP90和GRmRNA的表达无明显影响。结论 HSP90 /GR比例降低可影响Dex诱导的T细胞凋亡 ;Dex对哮喘患者GR和HSP90mRNA的表达有下调作用 ,而Dex的这一作用可被G
Objective To investigate the effect of dysregulated heat shock protein 90 (HSP90) and glucocorticoid receptor (GR) on the apoptosis of T lymphocytes and the effect of dexamethasone on the expression of HSP90 and GR mRNA. Methods Ten asthmatic patients and seven normal controls were selected. The effect of HSP90 was specifically blocked by geldanamycin (GA). The proportion of functional HSP90 and GR was decreased. Flow cytometry was performed with propidium iodide (PI) Apoptotic cells were counted to observe the apoptosis of T lymphocytes treated with Dex and GA. The effects of Dex and GA on the expression of HSP90 and GR mRNA in asthmatic T lymphocytes were observed by reverse transcriptase-polymerase chain reaction (RT-PCR) . Results Dex significantly induced apoptosis of T lymphocytes in asthmatic mice (33.8% ± 3.2% vs. 23.2% ± 15%, P <0.01). However, GA had no effect on the apoptosis of T lymphocytes Which could block the effect of Dex on T lymphocyte apoptosis (24.5% ± 6.0% vs 33.8% ± 3.2%, P <0.01). Dex could induce the apoptosis of normal human T lymphocytes , But to a lesser degree (259% ± 35% vs. 2311% ± 15%, P <0 05). Dex inhibited the expression of HSP90 and GR in T lymphocytes of asthmatic patients (123 ± 0.16 vs 168 ± 038 and 0 42 ± 0 0 6 vs 0 54 ± 0 0 7 respectively, P <0 0 5), GA has a blocking effect on this effect of Dex, but GA itself has no obvious effect on the expression of HSP90 and GR mRNA. Conclusions Decreased HSP90 / GR ratio may affect Dex-induced T cell apoptosis. Dex may down-regulate the expression of GR and HSP90 mRNA in asthmatic patients. Dex may be attenuated by G