跑台运动训练对脊髓损伤后大鼠肺损伤及HMGB1/TLR4/NF-κB信号通路表达的影响

Effects of treadmill training on lung injury and HMGB1/TLR-4/NF-κB signaling pathway after spinal cord injury in rats

目的:探讨跑台运动训练对脊髓损伤(SCI)后大鼠肺损伤及HMGB1/TLR4/NF-κB信号通路表达的影响。方法:选取54只SD雌性大鼠,随机分成3组,包括假手术组、SCI制动组、SCI运动组。SCI运动组及SCI制动组分别于术后第3天开始跑台运动训练或制动干预,BBB评分评定大鼠脊髓损伤后后肢运动功能。分别在运动或制动后第3天、第7天取肺组织,HE染色检测大鼠肺组织病理结构变化;免疫组化检测肺组织HMGB1蛋白表达情况;qRT-PCR检测HMGB1、TLR4、NF-κB、IL-1β、IL-6、TNF-α m RNA表达情况;Western Blot检测HMGB1、TLR4、NF-κB蛋白表达情况。结果:BBB评分结果显示,与假手术组比较,SCI制动组、SCI运动组BBB评分均显著下降(P<0.05);SCI运动组与SCI制动组评分结果比较无显著性差异(P>0.05)。HE染色结果显示,SCI制动组及SCI运动组第3天、第7天肺组织中均出现水肿、出血、炎性细胞浸润,相较于SCI制动组,SCI运动组肺损伤评分显著降低(P<0.05)。qRT-PCR、免疫组化、Western Blot结果均显示,与假手术比较,SCI制动组、SCI运动组第3天、第7天肺组织中HMGB1、TLR4、NF-κB、IL-1β、IL-6、TNF-α等因子的表达均显著上调(P<0.05),且SCI运动组较SCI制动组显著降低(P<0.05)。结论:跑台运动训练可改善脊髓损伤后大鼠肺损伤,其机制可能与调节HMGB1/TLR4/NF-κB信号通路,抑制肺组织炎症反应相关。

Objective:To explore the effect of treadmill training on lung injury and the expression of HMGB1/TLR4/NF-κB signaling pathway in rats after spinal cord injury(SCI).Method:Fifty-four SD female rats were selected and randomly divided into 3 groups,including sham operation group, SCI brake group, and SCI treadmill training group. The SCI treadmill training group and SCI brake group started treadmill training or braking respectively on the 3rd day after operation, the BBB score was used to evaluate the motor function of the hind limbs after the spinal cord injury in the rats. Lung tissues were taken on the 3rd and 7th day after treadmill training or braking, HE staining was used to detect the pathological changes of rats lung tissue,immunohistochemistry(IHC) was used to detect the expression of HMGB1 protein in lung tissue,qRT-PCR was used to detect HMGB1,TLR4,NF-κB,IL-1β,IL-6,TNF-αmRNA expression,Western Blot detection of HMGB1,TLR4,NF-κB protein expression.Result:The BBB score results showed that compared with the sham operation group,the BBB scores of the SCI brake group and the SCI treadmill training group decreased(P<0.05),and there is no statistical difference in the scores between the SCI exercise group and the SCI brake group(P>0.05). The results of HE staining of lung tissue showed that edema, hemorrhage, and inflammatory cell infiltration occurred in both the SCI brake group and the SCI treadmill training group on the 3rd day(P<0.05). The results of q RT-PCR,IHC,and Western Blot showed that the expressions of HMGB1,TLR4,NF-κB,IL-1β,IL-6,TNF-α and other factors were significantly up-regulated at each time point after SCI(P<0.05), and the SCI treadmill training group was significantly lower than the SCI brake group(P<0.05).Conclusion:Treadmill training can improve lung injury in rats after spinal cord injury. The mechanism may be related to the regulation of HMGB1/TLR4/NF-κB signaling pathway and inhibition of lung inflammation.