抑制PARP1活性对博来霉素诱导的肺纤维化的改善作用

发布时间：2018-07-03 18:23

本文选题：博莱霉素 + 肺纤维化　；参考：《吉林大学学报(医学版)》2015年03期

【摘要】：目的:探讨抑制聚ADP核糖多聚酶1(PARP1)活性对于博莱霉素导致的肺纤维化的改善作用,阐明抑制PARP1活化改善肺纤维化的作用机制。方法:48只雌性ICR小鼠随机分为对照组(腹腔注射生理盐水)和5、10、15mg·kg-1博莱霉素组(模型组)。3个模型组分别在第1、4、8、11、15、18、22和25天腹腔注射相应浓度的博莱霉素。60只雌性ICR小鼠随机分成对照组、10mg·kg-1博莱霉素模型组及不同剂量PARP1抑制剂PJ34治疗组(腹腔注射博来霉素20min前尾静脉注射1、5和10mg·kg-1 PJ34)。上述实验中,分别于第14、21和28天每组选取3只小鼠,处死后取肺。HE染色观察肺泡结构,Masson染色分析纤维化程度。肺上皮源性细胞A549用于博莱霉素刺激后,Real-time PCR法分析PJ34对上皮间充质转化(EMT)标志基因表达的影响。结果:与博莱霉素模型组比较,PJ34治疗组小鼠肺泡结构的破坏及胶原在肺间质中的沉积明显减轻;Realtime PCR法分析,与博莱霉素模型组比较,PJ34治疗组肺上皮细胞A549中E-cadherin mRNA表达水平升高(P0.05),α-SMA和TGF-βmRNA表达水平下降(P0.05或P0.01)。结论:抑制PARP1活性可以影响EMT标志基因的表达及肺纤维化的产生,PARP1抑制剂可用于预防博来霉素治疗肿瘤过程中产生的肺纤维化。
[Abstract]:Aim: to investigate the effect of inhibition of poly (ADP-ribose polymerase 1) (PARP1) activity on pulmonary fibrosis induced by bleomycin, and to elucidate the mechanism of inhibiting PARP1 activation to improve pulmonary fibrosis. Methods Forty eight female ICR mice were randomly divided into control group (intraperitoneal injection of normal saline) and bleomycin 51010mg kg-1 (model group). The rats were randomly divided into two groups: the control group (10 mg kg-1) and the control group treated with different doses of PARP1 inhibitor PJ34 (intraperitoneal injection of bleomycin 20min 1 5 and 10mg kg-1 PJ34 before caudal vein injection). Three mice were selected from each group on day 14, 21 and 28, respectively. After death, lung was stained with HE to observe the degree of fibrosis of alveolar structure by Masson staining. Lung epithelial-derived cell line A549 was used to detect the effect of PJ34 on the expression of EMT marker gene by real-time PCR after bleomycin stimulation. Results: compared with bleomycin model group, the destruction of alveolar structure and the deposition of collagen in interstitial tissue of PJ34 treated mice were significantly reduced by Realtime PCR. Compared with bleomycin model group, the expression of E-cadherin mRNA in lung epithelial cell A549 was increased (P0.05), and 伪 -SMA and TGF- 尾 mRNA levels were decreased in PJ34 treatment group (P0.05 or P0.01). Conclusion: inhibition of PARP1 activity may affect the expression of EMT marker gene and the production of pulmonary fibrosis. PARP1 inhibitor can be used to prevent pulmonary fibrosis caused by bleomycin in the treatment of tumor.
【作者单位】：吉林省疾病预防控制中心媒介生物防治科;东北师范大学遗传与细胞研究所;吉林大学体育学院;吉林大学中日联谊医院呼吸科;
【基金】：国家自然科学基金面上项目资助课题(31371293) 吉林省科技厅科技发展计划国际科技合作项目资助课题(20120728)
【分类号】：R965

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