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Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction

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Abstract

Objective

To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD).

Methods

According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot.

Results

Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01).

Conclusion

STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

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Authors and Affiliations

  1. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China

    Xin-yu Cui, Tian-hua Liu, Ya-li Bai, Meng-di Zhang, Guo-dong Li, Yu-ting Zhang, Ya-wen Zhang, Li-shuang Yu & Li-na Han

  2. Key Laboratory of Traditional Chinese Medicine Syndrome and Formula Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100029, China

    Xin-yu Cui, Tian-hua Liu, Ya-li Bai, Meng-di Zhang &  Yan Wu

  3. Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China

    Yue-ying Yuan &  Yan Wu

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  1. Xin-yu Cui
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  2. Tian-hua Liu
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Contributions

Cui XY and Bai YL performed the experiments and wrote the manuscript. Liu TH supervised this study. Zhang MD and Li GD analyzed data in this study. Zhang YT and Yuan YY provided technical support. Zhang YW, Yu LS and Han LN contributed to writing assistance and proofreading the manuscript. Wu Y made substantial contributions to the conception or design of the work. All authors read and approved the final manuscript for publication.

Corresponding author

Correspondence to Yan Wu.

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The authors declare that they have no conflicts of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81930113)

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Cui, Xy., Liu, Th., Bai, Yl. et al. Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction. Chin. J. Integr. Med. (2024). https://doi.org/10.1007/s11655-024-3658-z

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