Tetramethylpyrazine attenuates lipopolysaccharide-induced acute lung injury in mice by targeting the LIMK1/cofilin pathway through miR-143-3p
Object3ive To investigate the effect of tetramethylpyrazine(TMP)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice through miR-143-3p targeting and regulation of LIM kinase 1/filament cutin(LIMK1/cofilin)signaling pathway.Methods C57BL/6 mice were randomly divided into a control group(CON group),model group(LPS group),TMP group,null virus group(GFP group),overexpression of miR-143-3p group,and knockdown of miR-143-3p group,with 10 mice in each group.HE staining was used to observe the patho-logical changes of the lung histology;ELISA was used to detect the levels of interleukin 1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)in bronchoalveolar lavage fluid(BALF);lung wet/dry ratio(lung W/D),leukocyte count in BALF,protein concentration in BALF,and Evans Blue dye were used to detect lung vas-cular permeability;Western blot was used to detect the expression of p-LIMK1 and p-cofilin.Results Compared with the CON group,lung histopathological injury was aggravated in the LPS group,and the expression levels of lung injury score,lung W/D,BALF leukocyte counts,protein concentration and inflammatory factors,Ev-ans Blue leakage,p-LIMK1,and p-cofilin were increased(P＜0.01);compared with the LPS group,lung his-topathological injury in the group overexpressing miR-143-3p was attenuated,lung injury score,BALF leukocyte count,protein concentration and inflammatory factors,Evans Blue leakage were decreased(all P＜0.01),lung W/D was decreased(P＜0.05),and p-LIMK1,p-cofilin expression levels were decreased(P＜0.01,P＜0.05);compared with the LPS group,lung histopathological injury was attenuated in the TMP group,lung injury score,lung W/D,BALF leukocyte count,protein concentration and inflammatory factors,Evans Blue leakage were reduced(all P＜0.01),and the expression levels of p-LIMK1,p-cofilin were reduced(P＜0.01,P＜0.05);compared with the TMP group,the knockdown of miR-143-3p group reversed the effect of TMP on LPS-induced mouse ALI amelioration(all P＜0.01).Dual luciferase assay confirmed that miR-143-3p could target and regulate LIMK1 expression(P＜0.001).Conclusion TMP inhibited the LIMK1/cofilin signaling pathway by up-regulating miR-143-3p,thereby at-tenuating LPS-induced ALI in mice.
万方数据
维普
