| 张宁,徐永健,张珍祥,李超乾.核因子кB对支气管哮喘大鼠淋巴细胞增殖和凋亡的调节作用及雷公藤甲素对其影响[J].,2004,(5):435-438 |
| 核因子кB对支气管哮喘大鼠淋巴细胞增殖和凋亡的调节作用及雷公藤甲素对其影响 |
| Regulatory Function of Nuclear Factor кB on Lymphocyte Proliferation and Apoptosis in Bronchial Asthmatic Rats and Effect of Triptolide on the Regulation |
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| DOI： |
| 中文关键词: 支气管哮喘 核因子кB 雷公藤甲素 细胞增殖 细胞凋亡 |
| 英文关键词:bronchial asthma nuclear factor кB triptolide cell proliferation cell apoptosis |
| 基金项目:国家自然科学基金(No.30070332);教育部高等院校骨干教师资助计划(2000度)资助项目 |
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| 中文摘要: |
| 目的 探讨核因子кB(NF-кB)是否参与支气管哮喘淋巴细胞增殖和凋亡的调节过程以及雷公藤甲素对哮喘淋巴细胞增殖和凋亡的调控作用是否通过NF-кB发挥。方法 分别给予哮喘大鼠模型NF-кB抑制剂二硫代氨基甲酸吡咯烷(PDTC)和免疫抑制剂地塞米松及雷公藤甲素干预,进行病理检查、气道反应性测定,采用免疫荧光法检测肺组织和脾淋巴细胞NF-кB P65的表达,免疫组织化学法测定脾淋巴细胞增殖细胞核抗原(PCNA)、流式细胞术检测脾淋巴细胞凋亡,电泳迁移率改变试验测定NF-кB活性。结果 哮喘气道及脾淋巴细胞NF-кB的核表达量和活性均明显高于正常对照(均P<0.05);哮喘脾淋巴细胞的增殖率明显高于正常对照(P<0.05),而凋亡率明显低于正常对照(P<0.05);NF-кB抑制剂PDTC的应用可使哮喘异常上调的NF-кB核表达量及活性下降,脾淋巴细胞增殖减少、凋亡增多;且NF-кB活性与脾淋巴细胞的增殖率呈显著正相关(r=0.89,P<0.05),而与其凋亡率呈显著负相关(r=-0.54,P<0.05)。在体应用雷公藤甲素后,哮喘气道及脾淋巴细胞NF-кB的核表达量及活性、脾淋巴细胞的增殖率均明显下降(均P<0.05),而凋亡率明显增加(P<0.05),同时气道炎性细胞的浸润及气道高反应性亦明显减轻(均P<0.05),且气道嗜酸粒细胞的数量及气道的反应性与NF-кB活性呈 |
| 英文摘要: |
| To investigate whether nuclear factor кB (NF-кB) participates in the regulatory function of lymphocyte proliferation and apoptosis in bronchial asthma and whether the regulatory effect of triptolide on lymphocyte proliferation and apoptosis is conducted through NF-кB. Methods Intervention with dexametha-sone, triptolide and PDTC, a NF-кB inhibitor, were used to treat astmatic rats respectively. Pathological examination , airway response were determined, the NF-кB P65 expresssion in lung tissue and splenic lymphocytes by immunofluorescent assay were adopted, proliferative cell nuclear antigen (PCNA) in splenic lymphocytes was measured by immunohistochemistry, apoptosis of splenic lymphocytes were monitored by flow cytometry and NF-кB activity was investigated by electrophoresis mobility shift assay (EMSA). Results The nuclear expression and DNA binding activity of lung tissue and splenic lymphocytes in asthmatic rats were all significantly higher than those in the control (all P < 0.05), so was the proliferation rate of splenic lymphocytes (P < 0.05), while the apoptosis rate was much lower than that of normal control (P<0.05). Administration of PDTC could reduce the up-regulated expression and activity of NF-кB, the proliferation of splenic lymphocytes lowered, while the apoptosis increased. NF-кB activity showed an obviously positive correlation with proliferation of splenic lymphocytes ( r = 0. 89, P<0.05) and a significantly negative correlation with apoptosis rate (r=-0.54, P<0.05). After asthmatic rats had been treated with triptolide in vivo, the NF-кB nuclear expression and activity in airway and splenic lymphocytes, as well as the proliferation rate of splenic lymphocytes all lowered significantly (all P<0.05), the apoptosis rate increased significantly (P<0.05) , at the same time, the inflammatory cell infiltration and high reactivity of airway were significantly alleviated (both P<0.05). There were obviously positive correlation between the amount of airway eosinophils and reactivity with activity of NF-кB (r =0.79 and r = 0.68, P<0 .05), which indicated that the effect of triptolide was not significantly different from that of dexamethasone (P>0.05). Conclusion (1) NF-кB participates the formation of airway inflammation and hyper-reactivity in asthmatic rats by positive regulation on proliferation and negative regulation on apoptosis of lymphocytes. (2) Triptolide reduces airway inflammation by way of inhibiting NF-кB, and further inhibiting the proliferation of lymphocytes, so that to give full play of the role of anti-asthmatic airway inflammatory agents. Whether the molecular mechanism of triptolide in inhibiting NF-кB simulates that of gluco-corticoid needs further studying. |
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