实验性肺血栓栓塞症大鼠肺炎症反应的变化及阿托伐他汀的干预作用

The inflammatory response mechanism in experimental acute pulmonary thromboembolism rats and the intervention effect of atorvastatin

目的探讨实验性肺血栓栓塞症大鼠肺炎症反应的变化及阿托伐他汀的干预作用。方法 42只大鼠随机分为假手术组(Sham组)、肺栓塞模型组(PTE组)、阿托伐他汀干预组(Statin组)。采用自体血栓回输法建立肺栓塞大鼠动物模型,取动脉血行血气分析,取肺组织行常规病理检查,免疫组化测定P38促分裂原活化蛋白激酶(P38MAPK)及TNF-α在肺组织中的表达。结果 PTE组明显缺氧,且肺组织炎症损伤较Statin组明显。PTE组肺组织P38MAPK、TNF-α表达较Sham组表达增强,Statin组与PTE组相比表达减弱,差异均有统计学意义(P均<0.05)。结论急性肺动脉栓塞可引起P38MAPK信号通路参与的炎症反应的激活,阿托伐他汀可以从某种程度上抑制P38MAPK、TNF-α的表达,从而减轻炎症反应。

Objective To observe the inflammatory response mechanism in experimental acute pulmonary thromboem- bolism rats and the intervention effect of atorvastatin. Methods Forty-two 6-8 weeks-old male Wista rats were randomly divided into Sham group（n =6）, PTE model group（n = 18）, Statin group（n = 18）. The PTE models were established by intravenous injection of autologous blood clots. Rats in Statin group were intragastrically perfused with atorvastatin [ 10 mg/ （ kg day） ] for 7 days and rats in the other two groups were given equal saline. The arterial blood was extracted for blood- gas analysis. The pathological changes of the lung were examined under a light microscope. By using Immunohistochemis- try, the expression levels of P38MAPK and TNF-α were detected. Results The PaO2 degree in PTE group and Statin group were significantly lower than that in Sham group （ P 〈 O. 05 ）, and Statin group was significantly higher than PTE group （P 〈 0.05 ）. The levels of P38 MAPK and TNF-αexpression in lung tissue were significantly higher in PTE group and Statin group than in Sham group（ P 〈 0.05 ）. But the expression levels in Statin group were significantly lower than that in PTE group （P 〈 0.05 ）. Conclusions The acute pulmonary thromboembolism may be related to P38MAPK pathway, P38MAPK and TNF-α were activated. Atorvastatin can reduce the expression levels of P38MAPK and TNF-α and alleviate the inflammatory response. Atorvastatin should be considered in acute FFE therapy.