摘要
目的观察硫化氢(H2S)对博莱霉素所致大鼠肺纤维化的影响,并探讨其是否通过转化生长因子-β1(TGF-β1)/Smad信号通路发挥作用。方法 SD大鼠50只随机分为正常对照组、假手术组、模型组、硫氢化钠(Na HS)组和地塞米松组,每组10只,假手术组大鼠以生理盐水气管内注入,而后3组大鼠以博莱霉素A5气管内注入制备肺纤维化模型。自第2天起,Na HS组、地塞米松组大鼠分别以Na HS、地塞米松腹腔注射,其余3组腹腔注射等量生理盐水。全部大鼠第28天处死,留取肺组织,行HE和Masson染色,通过试剂盒测定肺组织羟脯氨酸(HYP)含量,采用实时荧光定量PCR和Western blot分别检测肺组织中TGF-β1、Smad2、Smad3、Smad7、α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)、Ⅲ型胶原(ColⅢ)m RNA和蛋白表达。结果与模型组比较,Na HS组和地塞米松组肺泡炎症与肺纤维化程度明显减轻(P<0.01)。与正常对照组或假手术组比较,模型组肺组织HYP含量以及TGF-β1、Smad 2、Smad 3、α-SMA、ColⅠ、ColⅢm RNA和蛋白表达水平升高,但Smad 7 m RNA和蛋白表达水平降低,差异均有统计学意义(P<0.01)。通过Na HS或地塞米松处理后,肺组织HYP含量以及TGF-β1、Smad 2、Smad 3、α-SMA、ColⅠ、ColⅢm RNA和蛋白表达水平减少,而Smad 7 m RNA和蛋白表达水平增加,与模型组比较,差异均有统计学意义(P<0.01)。然而,Na HS组与地塞米松组以及假手术组与正常对照组上述指标相比无显著性差异(P>0.05)。结论 H2S可能通过抑制TGF-β1/Smad信号转导通路下调α-SMA表达,从而减少ColⅠ、ColⅢ合成发挥抗大鼠肺纤维化作用。
To observe the influence of hydrogen sulfide（H2S） on bleomycin-induced pulmonary fibrosis in rats,and explore whether the effect is mediated by transforming growth factor-β1（TGF-β1） / Smad signaling pathway,total of 50 SD rats were recruited and randomly divided into normal control group, sham operated group, model group, sodium hydrosulfide（Na HS） group and dexamethasone group, with 10 animals in each group. Rats in sham operated group were intratracheally administered with normal saline, and rats in the latter 3 groups were intratracheally administered with bleomycin A5 to induce pulmonary fibrosis. From the second day, rats in Na HS group and dexamethasone group were injected intraperitoneally with Na HS and dexamethasone, respectively, while the rest of the 3 groups were injected intraperitoneally with isopyknic of normal saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson staining was performed. The contents of hydroxyproline（ HYP） in pulmonary tissues were measured with a commercial kit; the m RNA and protein expressions of TGF-β1, Smad2, Smad3, Smad7, α-smooth muscle actin（α-SMA）, collagen typeⅠ（ColⅠ） and collagen typeⅢ（ColⅢ） were detected by fluorescence real time quantitative PCR and Western blotting, respectively.In comparison with model group, pulmonary alveolitis and fibrosis in Na HS and dexamethasone groups were significantly alleviated（P〈0.01）; in comparison with normal control group or sham operated group,pulmonary tissue HYP contents, TGF-β1, Smad2,Smad3, α-SMA, Col Ⅰ, Col Ⅲ m RNA and protein expression was enhanced, but Smad7 m RNA and protein expression was decreased in model group（P〈0.01）. Upon treatment with Na HS or dexamethasone, pulmonary tissue HYP contents, TGF-β1, Smad2, Smad3, α-SMA, ColⅠ, ColⅢ m RNA and protein expression were reduced while Smad7 m RNA and protein expression were increased as compared to model group（P〈0.01）. Nevertheless, the above indicators were show
出处
《免疫学杂志》
CAS
CSCD
北大核心
2015年第12期1036-1041,共6页
Immunological Journal
基金
湖南省教育厅优秀青年项目(14B142)
湖南省教育厅重点项目(10A107)
