The effect of fasudil on the acute lung injury in rats induced by lipopolysaccharide
-
Corresponding author:
CHEN Qian-fen, cqf14621@126.com
-
Received Date:
2013-12-25
-
Abstract
Objective:To investigate the effects of fasudil on the acute lung injury(ALI) in rats induced by lipopolysaccharide(LPS) through the RhoA/Rho kinase pathway.Methods:Eighteen wistar rats were randomly divided into control group,LPS group and fasudil(FAS) group(6 rats each group).The ALI model was established by intraperitoneal injection of LPS 1 mg/kg for 16 hours,and then endotracheal instillation of LPS 3 mg/kg.The fasudil 10 mg/kg was intraperitoneally injected into FAS group at 30 min before intraperitoneal injection of LPS and 1 hour after endotracheal instillation of LPS.The rats were sacrificed after 3 hours.The morphological changes of lung tissue in 3 groups were observed by HE staining,the ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in 3 groups were measured,and the ROCK2(Rho kinase 2) mRNA and protein expressions in 3 groups were detected by reverse transcription-polymerase chain reaction and Western blot,respectively.Results:Compared with the control group,the lung histopathology change in LPS group was obvious,and the lung histopathology change in FAS group was significantly gentler than that in LPS group.The ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in LPS group were significantly higher than those in control group(P0.01),but the indexes in FAS and LPS group were decreased to varying degrees(P0.05 to P0.01).Compared with the control group,the ROCK2 mRNA expression of lung in LPS group was increased(P0.01),but the difference of which had no statistical significance between FAS and LPS group(P0.05).Compared with the control group,the ROCK2 protein expression in LPS group was significantly increased(P0.01).Compared with the LPS group,the ROCK2 protein expression in FAS group was significantly decreased(P0.05).Conclusions:Fasudil can reduce the acute lung injury in rats induced by lipopolysaccharide through the RhoA/Rho kinase signal pathway.
-
-
References
|
[1]
|
王绍谦，胡洋，张文田.乌司他丁对急性肺损伤患者炎症因子及血气分析的影响[J].中华实用诊断与治疗杂志，2011，25(2):157-159. |
|
[2] Vandenbroucke E，Mehta D，Minshall R，et al.Regulation of endothelial junctional permeability[J].Ann N Y Acad Sci，2008，1123(3):134-145. |
|
[3] Rikitake Y，Takai Y.Directional cell migration regulation by small G proteins，nectin-like molecule-5，and afadin[J].Int Rev Cell Mol Biol，2011，287:97-143. |
|
[4] Doe C，Bentley R.Behm DJ，et al.Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities[J].J Pharmacol Exp Ther.2007，320(1):89-98. |
|
[5] Wang HM，Bodenstein M，Markstaller K.Overview of the pathology of three widely used animalmodels of acute lung injury[J].Eur Surq Res，2008，40(4):305-316. |
|
[6] Zhou XH，Dai QC，Huang XL.Neutrophils in acute lung injury[J].Front Biosci，2012，17(1):2278-2283. |
|
[7] Bogatcheva NV，Verin AD.The role of cytoskeleton in the regulation of vascular endothlial barrier function[J].Microvasc Res，2008，76(3):202-207. |
|
[8] Mehta D，Malik AB.Signaling mechanisms regulating endothelial permeability[J].PhysiolRev，2006，86(1):279-367. |
|
[9] Schaafsma D，Bos IS，Zuidhof AB，et al.The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction，airway hyperresponsiveness，and inflammation[J].Am J Physiol Lung Cell Mol Physiol，2008，295(1):L214-L219. |
|
[10] Nagumo H，Sasaki Y，Ono Y，et al.Rho kinase inhibitor HA-1077 prevents Rho-mediatedmyosin phosphatase nhibition in smooth muscle cells[J].Am J Physiol Cell Physiol，2000，278(1):C57-C65. |
|
[11] Mueller BK，Mack H，Teusch N.Rho kinase，a promising drug targer for Neurological disorders[J].Nat Rev Drug Discov，2005，4(5):387-398. |
|
[12] 李刚，朱耀斌，续玉林，等.法舒地尔逆转大鼠重度肺动脉高压实验研究[J].中华实用诊断与治疗杂志，2012，26(3):230-233. |
|
[13] Tasaka S，Koh H，Yamada W，et al.Attenuation of endotoxin-induced acute lung injury by the Rho-associated kinase inhibitor，Y-27632[J].Am J Respir Cell Mol Biol，2005，32(6):504-510. |
|
[14] Meyer-Schwesinger C，Dehde S，Von Ruffer C，et al.Rho kinase inhibition attenuates LPS-induced renal failure in mice in part by attenuation of NF-B p65 signaling[J].Am J Physiol Renal Physiol，2009，296(5):F1088-F1099. |
-
-
Proportional views
-
DownLoad: