川芎嗪对内毒素诱导大鼠急性肺损伤的保护作用

目的：探讨川芎嗪（TMP）对内毒素（LPS）诱导大鼠急性肺损伤（ALI）的保护作用。方法：24只健康Wistar大鼠随机分为4组：对照组、LPS组、TMPⅠ组（40 mg/kg）和Ⅱ组（80 mg/kg）,每组各6只。腹腔注射LPS 1 mg/kg,16 h后再次气管滴注LPS 3 mg/kg,造成内毒素二次打击,建立大鼠ALI模型。于气管滴注LPS后3 h处死大鼠,4%多聚甲醛固定后制作病理切片,同时测肺湿/干重比,测量肺组织中髓过氧化物酶（MPO）活性、丙二醛（MDA）含量。Western-blot测肺组织中RhoA、ROCK2蛋白表达量,RT-PCR测肺组织中ROCK2 mRNA表达量。结果：与对照组比较,LPS组病理切片显示大鼠肺间质水肿,肺泡腔内可见出血及大量炎性细胞渗出,肺湿/干重比、MPO活性及MDA含量均明显增加（P〈0.01）,RhoA及ROCK2蛋白表达显著升高（P〈0.01）,ROCK2 mRNA表达明显升高（P〈0.01）。而TMPⅠ组和Ⅱ组的肺湿/干重比、MPO活性、MDA含量、RhoA及ROCK2指标均较LPS组显著减轻（P〈0.05~P〈0.01）,而TMPⅠ组和Ⅱ组上述各指标间差异均无统计学意义（P〉0.05）。结论：TMP对LPC诱导的大鼠ALI可能有保护作用。

Protective effect of tetramethylpyrazine on the acute lung injury induced by lipopolysaccharide in rat

Objective：To investigate the protective effects of tetramethylpyrazine（TMP） on the acute lung injury induced（ALI） by lipopolysaccharide（LPS） in rats. Methods： All rats were randomly into the control group,LPS group,TMP Ⅰ group（ injected with40 mg /kg） and TMP Ⅱ group（injected with 80 mg /kg）（6 rats each group）. The twenty-four ALI model Wistar rats were established by injecting 1 mg /kg of LPS into abdominal cavity,and dripping 3 mg /kg of LPS into trachea after 16 hours. The rats were sacrificed,fixed with 4% paraformaldehyde and treated with pathology at 3 hours after treatment with tetramethylpyrazine. The wet /dry weight ratio of lung and levels of MPO and MDA in lung tissues were measured. The protein expressions of RhoA and ROCK2,and mRNA expression of ROCK2 in lung tissues were detected using western-blot and RT-PCR,respectively. Results：Compared with the control group,the pathological section showed that the pulmonary interstitial edema,alveolar cavity bleeding,inflammatory cells exudate,wet /dry weight ratio of lung,MPO activity and MDA content increased significantly in LPS group（ P〈0. 01）,the protein expressions of RhoA and ROCK2,and mRNA expression of ROCK2 were also increased in LPS group（P〈0. 01）. The wet /dry weight ratio of lung,MPO activity,MDA content and indexes of RhoA and ROCK2 in TMP Ⅰ group and TMP Ⅱ group were significantly less than those in LPS group（P〈0. 05 to P〈0. 01）,but their differences between TMPⅠ group and TMP Ⅱ group were not statistical significance（P〈0. 05）. Conclusions：Tetramethylpyrazine can protect against the acute lung injury induced by LPS in rats.