川芎嗪对脓毒症急性肺损伤的保护作用

Protective effects of tetramethylpyrazine on endotoxin-induced acute lung injury

目的研究中药川芎嗪(Tetramethylpyrazine,TMP)对大鼠脓毒症相关急性肺损伤(acute lung injury,ALI)的保护作用。方法取健康雄性SD大鼠24只,随机分为空白组、LPS干预组(LPS组)、TM P治疗组(TM P组),每组8只。LPS组和TMP组分别给予腹腔注射LPS 20 mg/kg,空白组腹腔注射等量生理盐水,TMP组大鼠注射LPS 30 min后立即予TMP 80 mg/kg腹腔注射。4 h后,3组大鼠均经颈内动脉取血,后脱颈处死留取肺组织标本。测定动脉血气及肺组织湿/干重比,H-E染色观察肺组织病理形态,流式细胞术检测血浆中CD31+循环内皮微粒的表达水平,ELISA法检测血清中TNF-α水平,Western印迹法检测肺组织ROCKⅡ蛋白表达。结果 LPS组氧合指数均小于200,较空白组和TMP组均明显降低(P<0.05),TMP组较空白组减低(P<0.05)。肺组织切片HE染色光镜下可见LPS组肺泡结构紊乱,并可见弥漫性肺泡间隔增厚,而TM P组上述病理表现较LPS组明显减轻。TM P组平均肺泡壁厚度、肺组织湿/干重比值、血浆中CD31+内皮微粒表达量、血清中TNF-α水平及肺组织ROCKⅡ蛋白表达量均低于LPS组,差异有统计学意义(P<0.05);与空白组相比,差异无统计学意义(P>0.05),而LPS组上述指标均高于空白组,差异有统计学意义(P<0.05)。结论川芎嗪减轻LPS所致急性肺损伤大鼠肺渗出性病变,减轻肺组织炎症因子释放,对肺损伤起到积极保护作用,其对减轻肺渗出的作用可能与下调ROCKⅡ基因表达有关。

Objective To investigate the protective effect of Tetramethylpyrazine（TMP） on acute lunginjury（ ALI） induced by lipopolysaccharide（ LPS）. Methods Twenty four healthy male SD rats were randomly divided intoblank group,LPS control group,and TM P treatment group with 8 in each. LPS 20 mg/ kgwas intraperitoneally injected in LPS and TM P groups and same volume normal saline was given in control group,30 min late TM P 80 mg/ kgwas administrated intraperitoneally in TM P group. Blood samples were taken from internal carotid artery 4 hours after treatment; then the animals were sacrificed and lungtissue specimens were collected. Arterial blood gas analysis and lungwet / dry weight ratiowere determined. The histopathological features of lungwas observed under light microscope after H-E staining. CD31＋vascular endothelial particles in plasma was detected with flowcytometry; plasma TNF-α level was measured with ELISA,and the expression of ROCK Ⅱ protein was detected with Western blotting. Results Oxygenation index（ OI） in TM P treatment group was significantly higher than that in LPS group but lower than that in blank group（ P〈0. 05）.Histopathology showed that there were apparent structural disorder of alveoli and diffuse thickeningof alveolar sepata in lungsections of LPS group; the pathological changes were ameliorated in TM P treatment group. The average thickness of alveolar walls,the lungwet / dry ratio,the plasma CD31＋vascular endothelial particles and TNF-α levels and ROCK Ⅱ protein were all lower in TM P group than those in LPS group（ P〈0. 05）. There were nosignificant differences in above parameters between TM P treatment and blank groups（ P〉0. 05）. Conclusion Acute lunginjury can be alleviated by tetramethylpyrazine,which may be related todown-regulated expression of ROCK Ⅱ gene.