C型钠尿肽对百草枯致肺损伤小鼠TGF－β1／Smad4表达的影响

摘要

Objective To investigate the impact of C -type natriuretic peptide (CNP) on the expression of transfor-ming growth factor-β1 ( TGF-β1 ) and Smad4 in mice with paraquat -induced lung injury , in order to explore the mechanism of CNP to treat pulmonary fibrosis .Methods A total of 84 male Kun Ming mice were randomly divided into three groups (n=28):a control group, a paraquat (PQ) group and a CNP treatment (CNP) group.The PQ and CNP groups were intraperitoneally injected with 10 ml/kg paraquat , while the control group was intraperitoneally injected with the same volume of normal saline .On the first day of modeling , The CNP group was injected through the tail vein with 2 g/kg CNP, while the control and PQ groups were injected with the same volume of saline .The mice were sacrificed on Days 7, 14, 21 and 28, and the left lung tissues were collected to detect the level of Smad 4 by Western blotting.The level of TGF-β1 in the right lung tissues was measured by ELISA .Results Mice in the PQ group showed remarkably higher lung to body ratio than the control at each time point (P<0.05 or P<0.01).Compared with the PQ group, the lung to body ratio was markedly reduced in the CNP group at each time point (P<0.05 or P<0.01).The PQ group produced remarkably enhanced levels of TGF -β1and Smad4 in comparison with the control at each time point , which were then reduced after treatment with CNP (P<0.01 or P<0.05).Conclusion CNP can relieve the lung injury in-duced by paraquat , which may be associated with the expression of TGF -β1and Smad4.%目的：观察C型钠尿肽（ CNP ）对百草枯致肺损伤小鼠肺组织中转化生长因子－β1（ TGF－β1）和Smad4表达的影响，从而探讨CNP对肺损伤的作用机制。方法将84只雄性昆明小鼠随机分为对照组、百草枯模型组（ PQ组）和CNP治疗组（ CNP组），每组各28只。 PQ组和CNP组小鼠腹腔注射百草枯（10 mg／kg ），对照组腹腔注射等容积的生理盐水。从造模当天起，CNP组尾静脉注射CNP（3 g／kg），对照组和PQ组尾静脉注射等容积的生理盐水。于造模后7、14、21、28天分4批处死小鼠，每批6只，称量肺组织重量计算肺体系数。取左肺组织，采用Western blot测定肺组织中Smad4的表达。取右肺组织，采用ELISA法测定肺组织中TGF－β1的表达。结果 PQ组小鼠肺体系数较同时间点对照组明显增高（P＜0．05或P＜0．01）。与PQ组相比，CNP组小鼠肺体系数在各时间点均有所降低（P＜0．05或P＜0．01）。与对照组相比，PQ组肺组织中TGF－β1和Smad4表达明显增高（P＜0．01或P＜0．05）。与PQ组相比，CNP组肺组织中TGF－β1和Smad4表达比同时间点均有所降低（P＜0．01或P＜0．05）。结论 CNP能够减轻百草枯诱导的肺损伤的程度，其机制可能与TGF－β1／Smad4表达有关。