Mechanism of Mailuo Shutong Pill on anti-superficial thrombophlebitis based on TLR4/MyD88/MAPK signaling pathway
[Objective]To investigate the mechanism of Mailuo Shutong Pill on superficial thrombophlebitis.[Methods]A total of 36 Japanese white rabbits were randomly divided into normal group,model group,low,medium,high dose of Mailuo Shutong Pill group,and positive drug(Diosmin)group,with 6 rabbits in each group.Except the normal group,the rabbit model of superficial thrombophlebitis was established by injecting 20%mannitol into bilateral auricular vein of other groups.At the same time,the treated groups were respectively administrated through gavage once a day for 14 consecutive days.Pathological changes of rabbit ear tissue were detected by hematoxylin and eosin(HE)staining.The levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The semi-automatic hemagglutination analyzer was used to measure indicators of coagulation function.Expressions levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)were detected by western blotting.The protein expression and phosphorylation level of extracellular signal-regulated kinase(ERK1/2),p38 mitogen-activated protein kinase(p38MAPK)and c-amino acid terminal kinase(JNK)were detected by western blotting.[Results]The model group demonstrated increase in pathological injury score(P<0.01),significant decline in serum content of inflammatory factors IL-1β,TNF-α and IL-6(P<0.05);shortened activated partial thromboplastin time,prothrombin time(PT),and thrombin time(TT),while increased fibrinogen(FIB)content(P<0.05);increased the protein expression and the phosphorylation levels of TLR4,MyD88,MAPK(p38MAPK,ERK1/2 and JNK,P<0.01)compared with the normal group.While Mailuo Shutong Pill significantly reduced the score of pathological injury and improved the pathological injury of ear tissue(P<0.05 or P<0.01);significantly decreased the expression levels of IL-1β,TNF-α and IL-6 in serum(P<0.05 or P<0.01);prolonged APTT,PT and TT and decreased FIB content(P<0.05 or P<0.01);down-regulated the protein expression and phosphorylation level of TLR4,MyD88,MAPK(p38MAPK,ERK1/2 and JNK,P<0.05 or P<0.01)compared with the model group.[Conclusion]Mailuo Shutong Pill was able to inhibit the inflammatory response and improve blood coagulation function in a model rabbit with superficial thrombophlebitis,and the mechanism may be related to the inhibition of TLR4/MyD88/MAPK signaling pathway activation.
万方数据
维普
