丙戊酸钠减轻博莱霉素致大鼠肺纤维化

VPA alleviates bleomycin-induced pulmonary fibrosis in rats

目的:探讨丙戊酸钠在博莱霉素诱导的肺纤维化中的作用及机制。方法:42只大鼠随机分为正常对照组、模型组和治疗组。造模采用博来霉素5 mg/kg气管内注射,自造模14 d开始分别采用生理盐水(0.5m L/d)、丙戊酸钠(300 mg·kg-1·d-1)和地塞米松(0.6 mg·kg-1·d-1)腹腔内注射治疗14 d。模型组分别在造模后14和、28 d处死。治疗组在造模后28 d处死。然后通过HE染色、Masson染色、羟脯氨酸(HYP)检测和Western blotting检测α-平滑肌肌动蛋白(α-SMA)及E-钙黏蛋白(E-cadherin)表达的变化,综合分析丙戊酸钠对肺纤维化发展的干预作用。结果:HE染色显示丙戊酸钠治疗组的肺泡结构、肺间质的形态优于生理盐水组和地塞米松治疗组。Masson染色及HYP检测用于衡量肺组织内胶原的分布及含量,可见丙戊酸钠治疗组肺组织内胶原的分布及含量均显著低于地塞米松治疗组及生理盐水组。丙戊酸钠可以降低α-SMA的表达,同时上调上皮标志性蛋白E-cadherin的表达。结论:丙戊酸钠可以通过减少胶原的表达与分布及下调间充质蛋白α-SMA,同时上调上皮蛋白E-cadherin的表达从而减轻博来霉素诱导大鼠肺纤维化。

AIM：To investigate the effect of sodium valproate （ VPA） on bleomycin-induced pulmonary fibro-sis （ PF） and its mechanism.METHODS： SD rats （ n =42 ） were randomly divided into model group and treatment group.Bleomycin at dose of 5 mg/kg was intratracheally injected to establish a rat PF model.The rats in treatment group were given normal saline （NS, 0.5 mL/d）, VPA （300 mg· kg-1·d-1） or dexamethasone （DEX, 0.6 mg· kg-1· d-1 ） via intraperitoneal injection from the 14th day to the 28th day after modeling.The rats in model group were sacrificed on 0 d, 14 day and 28 d after modeling .The rats in treatment group were killed at 14th day after treatment.The effects of VPA on PF were evaluated by HE and Masson staining.The hydroxyproline （ HYP） content in the rat lung tissues was de-tected, and the expression ofα-smooth muscle actin （α-SMA） and E-cadherin was determined by Western blotting.RE-SULTS：HE staining showed that the alveolar structure and interstitial morphology in VPA group were better than those in NS group and DEX group.The level of collagen in VPA group was significantly lower than that in DEX group and NS group by determining the HYP content and Masson staining.VPA reduced the expression ofα-SMA, a mesenchymal marker pro-tein of PF, while increased the expression of epithelial marker protein E-cadherin.CONCLUSION：VPA reduces collagen content and distribution, and up-regulates the expression of the epithelial marker protein E-cadherin, while down-regulates mesenchymal marker proteinα-SMA, thereby preventing the rat lung tissues from bleomycin-induced PF.