【摘要】 目的阐明当归对放射性肺损伤过程中TGF-β₁水平的影响,寻求预防或治疗放射性肺损伤的有效途径。方法成年雌性C57BL6小鼠72只,随机分作4组（1）空白对照组9只,腹腔注射生理盐水20ml（kg·d）;（2）单纯当归组9只,腹腔注射25%当归注射液20ml（kg·d）;（3）单纯照射组27只,全肺单次照射12Gy+腹腔注射生理盐水20ml（kg·d）;（4）照射+当归组27只,全肺单次照射12Gy+腹腔注射25%当归注射液20ml（kg·d）。生理盐水和25%当归注射液于照射前1周开始注射,直至照射后2周结束。于照射后1、24和72h、1（潜伏期）、2、4、8、16（肺炎期）和24周（纤维化期）取实验组及相同鼠龄对照组小鼠肺组织,空白对照组与单纯当归组各1只,单纯照射组与照射+当归组各3只。左肺留作组织学与免疫组化分析。右肺作总RNA提取及实时定量RTPCR分析。结果空白对照组和单纯当归组动物,其免疫组化阳性细胞数相对较低,仅波动在9～31个之间。单纯照射组的阳性细胞数较上述两组明显增高（P<001）,尤以1周后为甚。照射+当归组的阳性细胞数则介于两者之间,也显著低于单纯照射组（P<001）。实时定量PCR结果显示,单纯照射组的TGFβ1mRNA相对含量较单纯当归组和空白对照组均有统计学意义（P<001）。照射+当归组的TGFβ1mRNA相对含量较单纯照射组明显下调。但后两组数值之间并无更多还原

【Abstract】 Objective To investigate the ability of Angelica Sinensis to affect the radiation-induced TGF-β₁ release in the animal model, so as to find an effective method to reduce the lung toxicity after thoracic irradiation. Methods The thoraces of C57BL/6 mice were exposed to either sham irradiation or single fraction of 12 Gy. Four study groups were defined: those that received neither irradiation nor Angelica Sinensis （NT group）, those that received Angelica Sinensis but no irradiation （AS group）, those that underwent irradiation without Angelica Sinensis （XRT group） and those that received both Angelica Sinensis and irradiation （AS/XRT group）. Treated and sham-irradiated control mice were sacrificed at times corresponding to the latent period （1, 24, 72 hours and 1 week postirradiation）, the pneumonic phase （2, 4, 8, and 16 weeks postirradiation）, and the beginning of the fibrotic phase （24 weeks postirradiation）. The TGF-β₁ mRNA expressions in the lung tissue were quantified by real-time quantitative reverse transcription polymerase chain reaction （RT-PCR）. Immunohistochemical Streptavidin-Peroxidase method and positive cell counting were used for objective quantification of TGF-β₁ protein expression. Results NT and AS groups exhibited low levels of TGF-β₁ protein expression with positive cell counts between 9 and 31. And there is an significantly elevated level of TGF-β₁ positive inflammatory cells in XRT group（P<0.01）. The number of the positive cells in AS/XRT group is between the NT and AS groups and the XRT-group, and the difference between AS/XRT group and XRT group was significant（P<0.01）. The results of qRT-PCR show that the relative mRNA expressions of cytokine TGF-β₁ in XRT group was significantly higher than the nonirradiated groups（P<0.01）, the lung tissue of the mice which were treated by Angelica Sinensis （AS/XRT group） revealed only a minor radiation-mediated TGF-β₁ response on mRNA level, but the statistical comparison of the TNF-α mRNA expression between the XRT and AS/XRT treatment-group was not significant（P=0.054）. Conclusion This study demonstrates a significant radiation-induced increase of TGF-β₁ （on mRNA and protein level） in the lung tissue, and the predominant localisation of TGF-β₁ in areas of inflammatory cell infiltrates suggests involvement of this cytokine in the pathogenesis of radiation-induced lung injury. In addition, we observed a pronounced decrease of mRNA and protein production of the TGF-β₁ in the AS/XRT group as compared to the XRT group. Therefore our results indicate that Angelica Sinensis down-regulates the radiation-induced TGF-β₁ release in the lung tissue, and it is maybe one of the possible mechanisms of this drug to reduce the lung toxicity after thoracic irradiation.;更多还原