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Mechanism of Mailuo Shutong Pill on anti-superficial thrombophlebitis based on TLR4/MyD88/MAPK signaling pathway |
Hits 540 Download times 345 Received:September 09, 2023 |
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DOI
10.11656/j.issn.1673-9043.2024.01.04 |
Key Words
Mailuo Shutong Pill;superficial thrombophlebitis;TLR4/MyD88/MAPK signaling pathway;mechanism |
Author Name | Affiliation | E-mail | WANG Qingguo | School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | CAO Ningning | Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China | | LI Shirong | New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China | | ZHANG Wanjing | National Cancer Center, National Clinical Research Center for Cancer, Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China | | SUN Chenghong | New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China | | YAO Jingchun | New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China | | ZHANG Guimin | New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd., Linyi 276000, China | lunanzhangguimin@yeah.net | XIAO Xuefeng | School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | kai1219@163.com |
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Abstract
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[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. |
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