基于络病学探讨内毒素“二次打击”急性肺损伤大鼠的Rho/ROCK机制及川芎嗪的保护作用

A Modified Lipolysaccharide“Two-hit”Induced Acute Lung Injury Model in Rats via Rho / ROCK Mechanism and Protective Effects of Tetramethylpyrazine on Injury Based on Collateral Disease Theory

目的:研究内毒素血症"瘀滞络脉"急性肺损伤大鼠的Rho/ROCK机制及川芎嗪的保护作用。方法:以内毒素"二次打击"建立大鼠内毒素血症"瘀滞络脉"急性肺损伤模型,分别设正常对照组、模型组、川芎嗪低剂量组、高剂量组,测定呼吸频率、肺泡灌洗液中性粒细胞(PMN)百分率、肺湿/干重比、肺组织髓过氧化物酶(Myeloperoxidase,MPO)活性、ROCK mRNA表达量,并观察、评估肺组织损伤严重程度。结果:与模型组相比,川芎嗪显著降低呼吸频率、PMN百分率、肺湿/干重比、MPO活性、ROCK mRNA表达量,减轻大鼠急性肺损伤病理改变。结论:川芎嗪可能通过抑制Rho/ROCK通路对内毒素血症"瘀滞络脉"大鼠急性肺损伤有较好的保护作用。

Objective： To investigate the protective effect of tetramethylpyrazine（ TMP） on acute lung injury（ ALI） in endotoxemia rats with ＂Collaterals Damaged by Toxic Stasis＂（ Yu Zhi Luo Mai） and its mechanism of Rho / ROCK. Methods： Endotoxemia rats model in ALI with Yu Zhi Luo Mai were established through lipolysaccharide＂two-hit＂. Rats were randomized into 4 groups： G1（ normal control group）,G2（ ＂two-hit＂group）,G3（ low dosage TMP group） and G4（ high dosage TMP group）. Measure the respiratory rate,lung wet / dry weight ratio,BALF PMN percentage,pulmonary MPO activity,ROCK2 mRNA expression quantity,observe and evaluate the severity of lung tissue injury. Results： Compared with the G2 rats,TMP significantly reduced respiratory rate,PMN percentage and lung wet / dry weight ratio,MPO activity and ROCK mRNA expression quantity,and reduced the pathological changes in endotoxemia rats with ALI. Conclusion： We found TMP might have better protection against ALI in endotoxemia rats with Yu Zhi Luo Mai through inhibiting Rho A / ROCK pathway.