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Mechanism research of Tangzhiqing Formula in alleviating diabetic atherosclerosis by improving cytoskeleton rearrangement in efferocytosis
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DOI   10.11656/j.issn.1672-1519.2025.11.15
Key Words   diabetic atherosclerosis;efferocytosis;cytoskeleton rearrangement;Tangzhiqing Formula
Author NameAffiliationE-mail
MIAO Yaodong Second Affiliated Hospital of Tianjin University of Traditional ChineseMedicine, Tianjin 300250, China  
LI Chun Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
SHAN Xinjue Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China 
 
MA Chuanrui First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China chuanruima2013@mail.nankai.edu.cn 
Abstract
    [Objective] To explore the mechanism of Tangzhiqing Formula(TZQ) in treating diabetic atherosclerosis. [Methods] Thirty-six male ApoE-/- mice were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish the diabetic atherosclerosis model. They were randomly divided into model group,Tangzhiqing Formula medium and high dose intervention groups,with 12 mice in each group. 0.9% sodium chloride solution 10 mL/(kg·d),medium dose Tangzhiqing Formula 4.23 g/(kg·d) and high dose Tangzhiqing Formula 8.46 g/(kg·d) were administered by gavage each day. Another 12 male ApoE-/- mice were fed with regular feed as the control group for 10 consecutive weeks. After the experiment,blood samples were taken to test the levels of blood glucose and blood lipids in mice;oil red O staining and HE staining were used to observe aortic atherosclerosis in mice;ELISA method was used to detect the levels of serum inflammatory factors C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),and interferon gamma(IFN-γ);QRT PCR and Western blot were used to measure the mRNA and protein expression levels of Ras homolog family member A(RhoA),Rho associated protein kinases 1 and 2(ROCK1,ROCK2),and other factors related to cytoskeletal rearrangement in aortic tissue. [Results] Compared with the control group,the model group mice showed symptoms such as mental fatigue,emaciation,wheezing,reduced mobility,yellow fur color,pale color of ears,nose,lips,and tongue,and loose and sticky stool. HE staining and oil red O staining showed an increase in aortic plaque area,random blood glucose and serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C) levels increased,serum inflammatory factors CRP,TNF-α,IFN-γ levels increased,and mRNA and protein expression levels of cytoskeleton rearrangement related factors RhoA,ROCK1,and ROCK2 increased(P<0.05 or P<0.01),indicating impaired efferocytosis function;compared with the model group,the mice in the medium and high-dose intervention groups of Tangzhiqing Formula showed general improvement,reduced aortic plaque area,decreased random blood glucose and serum TC,TG,and LDL-C levels,decreased serum inflammatory factors CRP,TNF-α,and IFN-γ levels,and decreased mRNA and protein expression of cytoskeleton rearrangement related factors RhoA,ROCK1,and ROCK2(P<0.05 or P<0.01),indicating improved efferocytosis effects;compared with the medium dose group,the high-dose group has more advantages in reducing aortic plaque area,lowering blood lipids and serum inflammatory factor levels,and improving efferocytosis effects(P<0.05 or P<0.01). [Conclusion] Tangzhiqing Formula may play an anti diabetic atherosclerosis role by down regulating the expression of cytoskeleton rearrangement related factors RhoA,ROCK1 and ROCK2,and improving the efferocytosis effect.

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