川芎嗪对脓毒症诱导的急性肺损伤小鼠血管内皮生长因子水平变化的影响

Effect of Tetramethylpyrazine on Vascular Endothelial Growth Factor Level of Mice with Acute Lung Injury Induced by Sepsis

目的研究川芎嗪(Tetramethylpyrazine,TMP)对脓毒症诱导的小鼠急性肺损伤(Acute lung injury,ALI)的保护作用以及对血管内皮生长因子(Vascular endothelial growth factor,VEGF)水平变化的影响。方法将小鼠随机分为假手术组(Sham组)、脓毒症组(Sep组)、治疗对照组(NS组)、TMP-A组和TMP-B组,Sep组、NS组、TMP-A组和TMP-B组采用盲肠结扎穿刺术(Cecal ligation and puncture,CLP)复制脓毒症相关性ALI模型,造模成功后,TMP-A组和TMP-B组分别经腹腔注射100 mg/kg和40 mg/kg TMP,Sham组和NS组经腹腔注射等量生理盐水,Sep组不作处理。分别于造模后0、12、24和48 h取材,HE染色观察小鼠肺组织病理学变化;ELISA检测小鼠血浆中VEGF含量变化;Western blot检测小鼠肺组织VEGF蛋白水平。结果 TMP组小鼠在造模后12 h时肺组织病理变化与Sep组相比有所减轻,24 h时肺泡水肿、肺出血及中性粒浸润均明显减轻,48 h时TMP作用最理想;TMP组小鼠血浆VEGF水平造模后24 h开始低于Sep组(P<0.05),48 h持续下降,已接近Sham组水平;TMP组小鼠肺组织VEGF蛋白水平在造模后24 h比Sep组明显升高,但低于Sham组(P<0.05);100 mg/kg TMP的效果优于40 mg/kg;小鼠肺组织VEGF水平与血浆VEGF水平呈负相关(P<0.05)。结论 TMP能够有效减轻脓毒症所致ALI,这一作用与降低血浆VEGF水平,恢复肺组织VEGF蛋白水平有关。

Objective To investigate the protective effect of tetramethylpyrazine（TMP） on the mice with acute lung injury（ALI） induced by sepsis as well as on the vascular endothelial growth factor（VEGF） level.Methods Mice were randomly divided into sham operation（Sham）,sepsis（Sep）,normal saline（NS）,TMP-A and TMP-B groups.The mouse model sepsis-induced ALI was copied by cecal ligation and puncture（CLP）.The mice in TMP-A and TMP-B groups were injected i.p.with TMP at dosages of 100 and 40 mg / kg respectively,and those in Sham and NS groups with an equal volume of normal saline,while those Sep group were untreated.The mice were observed for pathological change in lung tissue by HE staining 0,12,24 and 48 h after CLP,then determined for VEGF content in plasma by ELISA and for VEGF level in lung tissue by Western blot.Results Compared with in Sep group,the pathological changes in lung tissue of mice in TMP-A and TMP-B groups decreased 12 h,while the alveolar edema,lung hemorrhage and neutrophil infiltration decreased significantly 24 h after CLP.However,the effect of TMP was satisfactory 48 h after CLP.The VEGF contents in plasma of mice in TMP-A and TMP-B groups were lower than those in Sep group 24 h（P 0.05）,while decreased continuously to a level similar to that in Sham group 48 h after CLP.The VEGF levels in lung tissues of mice in TMP-A and TMP-B groups were significantly higher than that in Sep group 24 h after CLP but were lower than that in Sham group（P 0.05）.The curative effect of TMP at a dosage of 100 mg / kg was superior to that at a dosage of 40 mg / kg.The VEGF level in lung tissue was negatively related to that in plasma（P 0.05）.Conclusion TMP relieved the ALI induced by sepsis effectively,which might be associated with decreasing the VEGF level in plasma and recovering that in lung tissue.