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乌司他丁减轻老年大鼠髋部骨折后肺损伤程度的实验研究

Protective Effect and Its Possible Mechanism of Ulinastatin on Lung Injury Induced by Hip Fracture

  • 摘要: 目的 探讨乌司他丁减轻髋部骨折后肺损伤的作用及相关机制。方法 将24只10月龄SD大鼠随机分为对照组、实验组及干预组,每组8只,后2组制成左侧髋部骨折,其中干预组在造模前给予尾静脉注射乌司他丁50 000 U/kg。造模24 h后处死各组大鼠,检测各组实验动物血清中线粒体DNA(mtDNA)水平,肺泡灌洗液中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,肺组织中toll样受体-9(TLR9)、转录因子NF-κB表达水平,肺组织干湿质量比(W/D)、病理评分情况。结果 实验组大鼠血清中mtDNA水平,肺泡灌洗液中TNF-α、IL-6水平,肺组织中TLR9、NF-κB表达水平,肺组织W/D、病理评分情况均高于对照组( P<0.05);干预组大鼠血清中mtDNA水平,肺泡灌洗液中TNF-α、IL-6水平,肺组织中TLR9、NF-κB表达水平,肺组织W/D、病理评分情况均较实验组下降( P<0.05),但均未恢复至对照组水平( P<0.05)。结论 乌司他丁可能通过减少髋部骨折释放的mtDNA,进而降低肺组织中TLR9、NF-κB表达及下游的炎症因子水平,最终达到保护肺功能的作用。

     

    Abstract: Objective To investigate the protective effect and its possible mechanism of ulinastatin on lung injury caused by hip fracture. MethodsTotal 24 SD rats were randomly divided into control, hip fracture and hip fracture+ulinastatin groups (n=8). The rats of hip fracture and hip fracture+ulinastatin groups made the left hip fracture. The tail vein of rats of hip fracture+ulinastatin group were injected with 50 000 U/kg ustodin before made fracture model. Killed rats 24 h after mold building. Serum mtDNA, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in bronchoalveolar lavage fluid, Toll like receptor-9 (TLR9) and nuclear factor (NF)-κB protein expression in lung tissue, wet/dry ratio and pathological scores of lung were detected in all three groups. ResultsSerum mtDNA, TNF-α and IL-6 in bronchoalveolar lavage fluid, TLR9 and NF-κB protein expressions in lung tissue, wet/dry ratio and pathological scores of lung in hip fracture group were significantly higher than those in control group ( P<0.05). Ulinastatin significantly reduced the levels of serum mtDNA, TNF-α and IL-6 in bronchoalveolar lavage fluid, TLR9 and NF-κB protein expressions in lung tissue, as well as wet/dry ratio and pathological scores of lung ( P<0.05). ConclusionUlinastatin might could provide protection on lung injury in hip fracture, and mtDNA-TLR9-NF-κB pathway may play the role of reducing inflammatory level in the process.

     

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