Skip to main content
SpringerLink
Log in

Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus

  • Original Article
  • Published:
Medical & Biological Engineering & Computing Aims and scope Submit manuscript

Abstract

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42 °C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)–related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development.

Graphical abstract

A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat.

B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. Hartge MM, Kintscher U, Unger T (2006) Endothelial dysfunction and its role in diabetic vascular disease. Endocrinol Metab Clin N Am 35:551–560, viii–ix

    Article  CAS  Google Scholar 

  2. Schiekofer S, Galasso G, Sato K, Kraus BJ, Walsh K (2005) Impaired revascularization in a mouse model of type 2 diabetes is associated with dysregulation of a complex angiogenic-regulatory network. Arterioscler Thromb Vasc Biol 25:1603–1609

    Article  CAS  Google Scholar 

  3. Frisbee JC (2006) Vascular adrenergic tone and structural narrowing constrain reactive hyperemia in skeletal muscle of obese Zucker rats. Am J Physiol Heart Circ Physiol 290:H2066–H2074

    Article  CAS  Google Scholar 

  4. Rubanyi GM (1993) The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol 22(Suppl. 4):S1–S14

    Article  CAS  Google Scholar 

  5. Kolluru GK, Bir SC, Kevil CG (2012) Endothelial dysfunction and diabetes: effects on angiogenesis, vascular remodeling, and wound healing [J]. Int J Vasc Med 17(2):1–30

    Google Scholar 

  6. Roustit M, Cracowski JL (2012) Non-invasive assessment of skin microvascular function in humans: an insight into methods. Microcirculation 19:47–64

    Article  Google Scholar 

  7. Cracowski JL, Roustit M (2016) Current methods to assess human cutaneous blood flow: an updated focus on laser-based-techniques. Microcirculation 23:337–344

    Article  Google Scholar 

  8. Hebe DK, Stefanovska A, Bracic M et al (1998) Spectral analysis of the laser Doppler perfusion signal in human skin before and after exercise[J]. Microvasc Res 56(3):173–182

    Article  Google Scholar 

  9. Hebe DK, Stefanovska A, Knut AK et al (1999) Oscillations in the human cutaneous blood perfusion signal modified by endothelium-dependent and endothelium-independent vasodilators[J]. Microvasc Res 57(3):298–309

    Article  Google Scholar 

  10. Stefanovska A, Bracic M, Kvernmo HD (1999) Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique. IEEE Trans Biomed Eng 46:1230–1239

    Article  CAS  Google Scholar 

  11. Smirnova E, Podtaev S, Mizeva I, Loran E (2013) Assessment of endothelial dysfunction in patients with impaired glucose tolerance during a cold pressor test [J]. Diab Vasc Dis Res 10(6):489–497

    Article  Google Scholar 

  12. Benedict KF, Coffin GS, Barrett EJ, Skalak TC (2011) Hemodynamic systems analysis of capillary network remodeling during the progression of type 2 diabetes [J]. Microcirculation 18(1):63–73

    Article  Google Scholar 

  13. Fu X, Gens JS, Glazier JA, Burns SA, Gast TJ (2016) Progression of diabetic capillary occlusion: a model[J]. PLoS Comput Biol NLM 12(6):e1004932

    Article  Google Scholar 

  14. Zeller-Plumhoff B, Roose T, Clough GF et al (2017) Image-based modelling of skeletal muscle oxygenation[J]. J R Soc Interface 14(127)

  15. Tang YL, Mu LZ, He Y (2020) Numerical simulation of fluid and heat transfer in a biological tissue using an immersed boundary method mimicking the exact structure of the microvascular network. Fluid Dynam Mater Process 16(2):281–296

    Article  Google Scholar 

  16. Tang YL (2017) Mechanism study of thermal methods for the detection of diabetic microvascular dysfunction [D]. Dalian University of Technology

  17. Padilla DJ, Mcdonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, Poole DC (2006) Effects of type II diabetes on capillary hemodynamics in skeletal muscle [J]. Am J Physiol-Heart C 291(5):2439–2444

    Article  Google Scholar 

  18. Guo Y, Ren D (2005) Basic and experimental methods of microcirculation. Fourth Military Medical University Press, Xi’an

    Google Scholar 

  19. Lu Y-X, Zhang Q, Li J, Sun Y-X, Wang y L-Y, Cheng y W-M, Xiang-Yang H (2010) Antidiabetic effects of total flavonoids from Litsea Coreana leve on fat-fed, streptozotocin-induced type 2 diabetic rats. Am J Chin Med NLM 38(4):713–725

    Article  CAS  Google Scholar 

  20. Wu J, Molecular mechanisms and effects of rosiglitazone on endothelium-dependent vasodilation in type 2 diabetes, Central South University, PhD thesis, 2006

  21. Wang YP, Mu LZ, He Y, Tang YL, Liu C, Lu YX, Xu LS (2020) Heat transfer analysis of blood perfusion in diabetic rats using a genetic algorithm. Micorvas Res 131:104013

    Article  CAS  Google Scholar 

  22. Geyer MJ, Jan YK, Brienza DM, Boninger ML (2004) Using wavelet analysis to characterize the thermoregulatory mechanisms of sacral skin blood flow. J Rehabil Res Dev 41:797–806

    Article  Google Scholar 

  23. Li Z, Tam EWC, Lau RYC et al (2009) Post pressure response of skin blood flow motions in anesthetized rats with spinal cord injury. Microvasc Res 78(1):20–24

    Article  Google Scholar 

  24. Kvandal P, Landsverk S, Bernjak A, Stefanovska A, Kvernmo H, Kirkeb K (2006) Low-frequency oscillations of the laser Doppler perfusion signal in human skin. Microvasc Res 72(3):120–127

    Article  Google Scholar 

  25. Wang YP, Tang YL, He Y Numerical analysis of the influence of RBCs on oxygen transport within a tissue with an embedded capillary network, Proc. IMechE. Part C: J Mech Eng and Sci

  26. Ciasca G, Papi M, Di Claudio S, Chiarpotto M, Palmieri V, Maulucci G, Nocca G, Rossib C, De Spirito M (2015) Mapping viscoelastic properties of healthy and pathological red blood cells at the nanoscale level. Nanoscale. https://doi.org/10.1039/c5nr03145a

  27. Yong J, Ruan P, Feng B, Shi M, Peng L (2013) Study on the relevance of changes in red blood cell morphology and function of patients with diabetic nephropathy to the development of diabetes. J Jinan Univ(Med Ed) 34(6):610–614

    Google Scholar 

  28. Wei YJ, Mu LZ, Tang YL, He Y, Shen ZY (2019) Computational analysis of nitric oxide biotransport in capillary influenced by multiple red blood cells. Microvasc Res 125:103878

    Article  CAS  Google Scholar 

  29. Cunningham KS, Gotlieb AI (2001) The role of shear stress in the pathogenesis of Lab Invest. 85:9–23

  30. Caballero AE, Arora S, Saouaf R, Lim SC, Smakowski P, Park JL, King GL, LoGerfo FW, Horton ES, Veves A (1999) Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 48:1856–1862

    Article  CAS  Google Scholar 

  31. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H (1999) Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 34:146–154

    Article  CAS  Google Scholar 

  32. Schmoelzer I, Wascher TC (2006) Effect of repaglinide on endothelial dysfunction during a glucose tolerance test in subjects with impaired glucose tolerance. Cardiovasc Diabetol 5:9

    Article  Google Scholar 

  33. Triggle CR, Hollenberg M, Anderson TJ, Ding H, Jiang Y, Ceroni L, Wiehler WB, Ng ESM, Ellis A, Andrews K, McGuire JJ, Pannir-selvam M (2003) The endothelium in health and disease—a target for therapeutic intervention. J Smooth Muscle Res 39:249–267

    Article  CAS  Google Scholar 

  34. Komers R, Anderson S (2003) Paradoxes of nitric oxide in the diabetic kidney. Am J Physiol Ren Physiol 284:F1121–F1137

    Article  CAS  Google Scholar 

  35. Martin A, Komada MR, Sane DC (2010) Abnormal angiogenesis in diabetes mellitus[J]. Med Res Rev 23(2):117–145

    Article  Google Scholar 

  36. Van de Zee R, Murohara T, Luo Z et al (1997) Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium[J]. Circulation 95(4):1030–1037

    Article  Google Scholar 

  37. Inoue N, Venema RC, Sayegh HS et al (1995) Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor–β1[J]. Arterioscler Thromb Vasc Biol 15(8):1255–1261

    Article  CAS  Google Scholar 

  38. Taylor GI, Minabe T (1992) The angiosomes of the mammals and other vertebrates[J]. Plast Reconstr Surg 89(2):181–215

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (No. 51976026), Dalian Innovative Funding of Science and Technology (2018J12SN076), and the Fundamental Research Funds for the Central Universities (DUT20GJ203).

Author information

Authors and Affiliations

  1. School of Energy and Power Engineering, Dalian University of Technology, Dalian, 116023, China

    Yajie Wei, Huimin Chen, Qingzhuo Chi, Ying He & Lizhong Mu

  2. Anhui Medical University, Hefei, China

    Chao Liu & Yunxia Lu

Authors
  1. Yajie Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huimin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qingzhuo Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lizhong Mu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yunxia Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying He.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, Y., Chen, H., Chi, Q. et al. Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus. Med Biol Eng Comput 59, 1151–1166 (2021). https://doi.org/10.1007/s11517-021-02363-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11517-021-02363-5

Keywords

Search

Navigation