摘要
目的探讨还原型谷胱甘肽（GSH）对博莱霉素（BLM）致肺纤维化的保护作用和可能机制。方法将40只SD大鼠按随机数字表法分为对照组、模型组、地塞米松组及GSH组，每组10只。采用气管内滴注博莱霉素5mg／kg诱导大鼠肺纤维化模型；对照组气管内滴注生理盐水2mud。24h后，模型组、地塞米松组及GSH组分别腹腔内注射生理盐水2mL／d、地塞米松1mg·kg^-1·d^-1及GSH120mg·kg^-1·d^-1进行干预。制模28d处死大鼠取肺组织，苏木素-伊红（HE）染色评价肺组织病理学改变；Masson染色评价肺间质纤维化程度；免疫组化染色检测肺组织仅-平滑肌肌动蛋白（α-SMA）表达水平；反转录-聚合酶链反应（RT—PCR）测定肺组织转化生长因子-β1（TGF-β1）及Smad3和Smad7的mRNA表达。结果光镜下可见对照组肺组织结构完整，无炎性细胞浸润；模型组肺组织大片肺泡结构破坏，肺泡间隔明显增厚，可见大量炎性细胞浸润；GSH组与地塞米松组肺组织病理改变较模型组减轻，以GSH组肺泡炎及肺纤维化程度减轻更显著。与对照组比较，模型组肺组织胶原纤维染色面积显著增加（μm2：127．47±6．98比39．29±5．42），α-SMA表达明显升高[吸光度（4）值：12．22±1．21比1．97±0．75]，TGF-β1与Smad3的mRNA表达明显减少，Smad7的mRNA表达明显增多（对照组为1，TGF-β1、Smad3、Smad7的mRNA相对表达量分别为5．79±0．61、8．49±0．38、0．32±0．05，均P〈0．01）。地塞米松与GSH干预均可减轻上述损伤效应，以GSH组改善更为显著，GSH组肺组织胶原纤维染色面积（87．81±7．71）、饯-SMA表达（8．34±1．48）、TGF-β1mRNA（1．58±0．22）、Smad3mRNA（2．21±0．19）、Smad7mRNA（0．87±0．04）表达水平与模型组比较差异均有统计学意义（均P〈0．05）。结论GSH早期应用可能通过抑制TGF-β1、Smad3的表达及促进Smad7的表达来发挥对BLM致�
Objective To study the protective effect of reduced glutathione hormone （GSH） on pulmonary fibrosis induced by bleomycin in rats and the possible mechanism. Methods Forty healthy male Sprage-Dawley （SD） rats were randomly divided into control, model, GSH and dexamethasone groups by using random number table, 10 in each group. The rat model of pulmonary fibrosis was induced by intratracheal instillation of 5 mg/kg bleomycin, while the control group received intratracheal instillation of 2 mL/d normal saline. After 24 hours, the model, dexamethasone and GSH groups were interfered with intra-peritoneal injection of 2 mL/d normal saline, 1 mg· kg^-1· d^-1 dexamethasone and 120 mg· kg^-1· d^-1 GSH respectively. All rats were killed on the 28th day after modeling and their lung tissues were collected, the pathological changes of the lungs were evaluated by hematoxylin-eosin （HE） stain, the degree of pulmonary interstitial fibrosis was assessed by Masson stain, and the immunohistochemistry was used to detect the expressions of α-smooth muscle actin （α -SMA） in the rat lung tissues. The mRNA expressions of transforming growth factor -β 1 （TGF-β 1）, Smad3, and Smad7 in lung tissues were measured by reverse transcription-polymerase chain reaction （RT-PCR）. Results Under a light microscope, it was shown that the lung tissue structure in the control group was normal and complete without any inflammatory cells infiltration; in the model group, there were large patches of pulmonary alveoli destruction in lung tissue, extensive thickening of alveolar wails and a large amount of inflammatory cells infiltration; in the dexamethasone group and GSH group, the pathological changes of lung tissue were milder than those in model group, and the degree of amelioration of pulmonary alveolitis and fibrosis in GSH group was more significant. Compared with control group, the staining area of collagen fiber in the model group was significantly increased （μ m2：127.47 ± 6.98 vs. 39.29 ± 5.42）, the expre
出处
《中国中西医结合急救杂志》
CAS
北大核心
2016年第2期143-146,共4页
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
基金
山东省自然科学基金资助项目（ZR2014HM112）
山东省教育厅科技发展项目（J08LG03）
