Study on the Mechanism of Resveratrol Attenuating LPS-induced Acute Lung Injury in Mice Based on TLR 4/ NF-κB Pathway / 中国药房

ABSTRACT

OBJECTIVE：To observe the p rotective effects of resveratrol （Res）on LPS-induced acute lung injury （ALI）model mice，and to explore its possible mechanism based on TLR 4/NF-κB pathway. METHODS：Kunming mice were divided into normal group，model group ，positive control group （dexamethasone，0.5 mg/kg），Res low-dose ，medium-dose and high-dose groups （50， 100，200 mg/kg），with 10 mice in each group. Normal group and model group were given normal saline intragastrically ，once a day，for 7 days；positive control group were intraperitoneally injected with Dexamethasone sodium phosphate injection ，once a day，for 3 days；Res groups were given relevant medicine intragastrically ，once a day ，for 7 days. After last administration ，all the mice except the normal group were dripped LPS （5 mg/kg）into the nose to induce ALI model. The apoptosis of neutrophils in BALF was observed by Hoechst 33242 staining；the apoptosis rate of neutrophils were detected by flow cytometry. The contents of IL- 6 and TNF-α in the plasma were detected by ELISA. After wet mass to dry mass （W/D）ratio of lung was E-mail：492234709@qq.com calculated，the morphological characteristics of lung tissue were observed by HE staining. Western blotting assay was used to detect the expression o f TLR 4 and NF-κ B in lung tissue. RESULTS ：In normal group ，there were few apoptotic neutrophils in the BALF ，and the lung tissue structure was intact ， without edema，hyperemia，exudation，inflammatory cell infiltration or other inflammatory manifestations. In model group ，the number of apoptotic neutrophils in BALF increased ，and the apoptotic rate of neutrophils were enhanced significantly （P＜0.01）； edema and hyperemia of lung tissue were significantly increased ，and the red consolidation area was observed ；the contents of IL- 6 and TNF-α in plasma，the ratio of lung W/D，the relative expression of TLR 4 and NF-κB in lung tissue were significantly increased （P＜0.01）. Compared with model group ，the number of apoptotic neutrophils in BALF were increased ，and the apoptotic rate of neutrophils were enhanced significantly （P＜0.05 or P＜0.01）above symptoms of lung tissue were improved to different extents ； the contents of IL- 6 and TNF-α in plasma，lung W/D ratio as well as relative expression of TLR 4 and NF-κB in lung tissue（except for Res low-dose group ）in administration groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Res has a protective effect on ALI model mice ，the mechanism of which may be related to reducing the generation of inflammatory cytokines TNF-α and IL-6 by inhibiting TLR 4/NF-kB expression.