抑制活化素受体样激酶5对严重烧伤大鼠急性肺损伤的影响

目的研究TGF-β/Smads信号转导通路对烧伤大鼠急性肺损伤后促炎性细胞因子的表达和肺部炎性损伤程度的影响,以了解该信号转导通路在肺纤维化发生的早期过程中的作用。方法用SB431542抑制活化素受体样激酶5(ALK5)来抑制TGF-β/Smads通路。将24只雄性SD大鼠,随机分为对照组、烧伤组、早期处理组、后期处理组,每组6只。除对照组外,其他3组大鼠麻醉后以98℃水烫背部15 s,造成大鼠30%TBSAⅢ度烧伤,烧伤后腹腔注射40 ml/kg乳酸林格液进行液体复苏,对照组施行假烫,背部浸入37℃水中,未补液。早期处理组分别于烧伤后、1×24 h、2×24 h后腹腔注射SB431542,后期处理组分别于3×24 h、4×24 h、5×24 h后腹腔注射SB431542,7 d后取肺组织,采用Realtime PCR法检测TNF-α和IL-1β的mRNA转录水平,并行肺脏病理学检查及Szapiel评分。结果早期抑制ALK5可提高TNF-α和IL-1βmRNA的转录水平,病理学观察见早期抑制ALK5能加重肺泡炎,急性期后抑制不会加重肺泡炎。结论TGF-β/Smads信号转导通路参与了烧伤后的肺部炎症反应,早期抑制该通路可上调促炎性细胞因子TNF-α和IL-1βmRNA的转录水平,最终增加TNF-α和IL-1β的表达,加重烧伤后的肺损伤;而在炎症反应的急性期后抑制该通路不会加重肺损伤。

Inhibition of activin receptor-like kinase 5 affects acute lung injury of severely burnt rats

Objective To investigate the potential roles of Smads signal transduction pathway in earlier period of pulmonary fibrosis formation by investigating the expression of proinflammatory cytokines and extent of inflammatory lung injury.Methods Twenty-four SD rats were randomly divided into group of control,burn,SB431542 early treatment and SB431542 later treatment with 6 rats for each.Rats other than in the control group were burnt at 98℃ for 15 s with a constant burning apparatus to prepare for the 3rd degree burns of 30% of total body surface area（TBSA）,and rats of the control group were burnt in water at 37℃ for 15s.Rats of the control group received no fluid resuscitation,while rats of the other groups were abdominally administrated with lactated Ringer′s solution at 40 ml/kg body weight for fluid resuscitation respectively after the burn.Rats of early treatment group were treated with SB431542 immediately,at 1×24 h and 2×24 h after the burn respectively.Rats of later treatment group were treated with SB431542 at 3×24 h,4×24 h and 5×24 h after the burn respectively.The lungs of all rats were obtained at 7 d after the burn.The mRNA expression of TNF-α and IL-1β in the tissues of lung were tested by real time PCR.Lung specimens were also double blindly examined and evaluated by Szapiel′s pathological scores.Results Early inhibition of activin receptor-like kinase 5（ALK5） increased production of TNF-α and IL-1β mRNA.Pathological changes suggested that inflammatory response could be increased by the early inhibition of ALK5 but not the late one.Conclusions Smads signal transduction pathway involved in the inflammatory response of lung tissue after burn.In the acute phase response of inflammatory lung injury,early inhibition of ALK5 could increase mRNA production of TNF-α and IL-1β,which further increased the expression of proinflammatory cytokines,and aggravated burn-induced inflammatory lung injury,while late inhibition of which did not show the effects.