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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。
Objective To study the effect of TGF-β / Smads signaling pathway on the expression of proinflammatory cytokines and inflammatory injury in lungs after acute lung injury in burn rats in order to understand the role of TGF-β / Smads signal transduction pathway in the early stage of pulmonary fibrosis The role of the process. Methods SB431542 inhibits activin receptor-like kinase 5 (ALK5) to inhibit TGF-β / Smads pathway. Twenty-four male Sprague-Dawley rats were randomly divided into control group, burn group, early treatment group and post-treatment group, with 6 rats in each group. In addition to the control group, the other three groups of rats were anesthetized and then dorsal the back at 98 ℃ for 15 s, resulting in 30% TBSA degree burn in rats. After the burn, 40 ml / kg lactated Ringer’s solution was intraperitoneally injected for liquid resuscitation. Hot, dipped in 37 ℃ water back, did not rehydration. The rats in the early treatment group were intraperitoneally injected with SB431542 at 1 × 24 h and 2 × 24 h respectively after burn, and the rats in the latter group were injected with SB431542 at 4 × 24 h, 4 × 24 h and 5 × 24 h respectively Lung tissues were detected by Realtime PCR. The mRNA levels of TNF-α and IL-1β were detected by real-time PCR. Pulmonary pathological examination and Szapiel score were performed. Results Early inhibition of ALK5 could increase the transcriptional level of TNF-αand IL-1βmRNA. Pathological observation showed that inhibition of ALK5 could exacerbate alveolitis in the early stage, and inhibition of acute phase did not aggravate alveolitis. Conclusion TGF-β / Smads signal transduction pathways are involved in lung inflammation after burn injury. Early inhibition of this pathway up-regulates the transcription of proinflammatory cytokines TNF-α and IL-1βmRNA, finally increases the levels of TNF-αand IL- 1β expression, aggravating lung injury after burn; inhibiting this pathway does not aggravate lung injury after the acute phase of inflammatory reaction.