Protection Of Gentiopicroside On Acute Lung Injury In Sepsis Mice

Objective:To observe the protective effect of gentiopicroside onsepsis-induced acute lung injury in mice and investigate possible mechanism.Methods: The mouse model of septic acute lung injury was establishedby ceceal ligation and puncture (CLP).18~22g male mice were randomlydivided into sham operation group, model group, low-dose ofgentiopicroside group(25mg/kg), high-dose of gentiopicroside group(50mg/kg). The mice were separately given a tail vein injection ofgentiopicroside or normal saline0.5h before CLP.12h after operation, thecontents of the inflammatory factors(TNF-α,IL-6) and total protein in thebronchoalveolar lavage fluid(BALF) were determined by ELISA; the levels ofmalondialdehyde (MDA), myeloperxidase (MPO), inducible nitric (iNOS)and NO in lung tissue were determined by biochemistry method; Thehistopathological changes of the lung tissue were observed under the lightmicroscope; The expressions of TLR4and NF-κB in lung tissue weredectected by Western Blot.Results: Compared with the sham group, the levels of MDA, MPO, iNOS, NO in lung tissue,the contents of TNF-α, IL-6and total proteinin BLAF were increased significantly(P <0.05or0.01), pulmonary interstitialwas congestion and edema, massive neutrophils cells and red blood cellsinfiltration, alveolar structure destruction in the model group at12h afteroperation; Compared with the model group, the levels of MDA, MPO,iNOS, NO in lung tissue and the contents of TNF-α, IL-6and totalprotein in BLAF were decreased significantly(P <0.05or0.01), thepathological injury was obversely improved in the low and high dose ofgentiopicroside groups. Compared with the sham group, the expressions ofTLR4and NF-κB in lung tissue were up-regulated significantly in modelgroup at12h after CLP; but compared with the model group, theexpressions of TLR4and NF-κB were down-regulated significantly in thelow and high dose of gentiopicroside groups, especially in high dose group,and the down-regulation of NF-κB was more significant than that ofTLR4.Conclucion: Gentiopicroside could attenuate inflammation reaction inlung tissue of mice with septic acute lung injury, and the effect is probablyassociated with the inhibition of the over expression of TLR4and NF-κBactivation.