Morphometric parameters of sinusoidal capillaries, interlobular veins and interlobular arteries at different stages of experimental liver fibrosis
https://doi.org/10.18499/2225-7357-2022-11-3-32-38
Abstract
The aim of the study was to conduct a morphometric analysis of sinusoidal capillaries, interlobular veins and interlobular arteries of the liver at different stages of experimental fibrosis in order to investigate relationship between fibrogenesis and angiogenesis and identify new therapeutic targets.
Material and methods. The study included male Wistar rats. Liver fibrosis with transformation into cirrhosis was induced with a solution of thioacetamide, which was injected into the stomach, dosage 200 mg/kg of animal body weight, using a probe 2 times a week. The rats of the experimental groups were withdrawn from the experiment in 3, 5, 7, 9, 11, 13, 15, and 17 weeks, and the intact ones - at the end of the experiment. To identify connective tissue, liver sections were stained according to the Mallory method. Immunohistochemical examination was performed on paraffin sections using a monoclonal mouse antibody to CD31. The number of sinusoidal capillaries, interlobular arteries, and interlobular veins was counted in three non-overlapping fields of view of each histological section using an OLYMPUS BX51 microscope at a 40× objective magnification.
Results. The results obtained supported a statistically significant decreased number of sinusoidal capillaries (p=0,0000) and an increased number of interlobular veins (p=0,0000) in animals of the experimental group compared with the control group. There were no differences in the number of interlobular arteries (p=0,9999). Pronounced angiogenesis in the portal zones and connective tissue septa was associated with an increased amount of the connective tissue during liver fibrogenesis.
Conclusion. In the future, angiogenesis modulation should be differentiated and directed towards antifibrotic, anti-inflammatory or autoimmune therapy in chronic liver diseases.
Keywords
About the Author
E. I. LebedevaBelarus
Elena I. Lebedeva – Assoc. Prof. of department of histology, cytology and embryology
Prospekt Frunze, 27, Vitebsk, 210009
References
1. Acharya P., Chouhan K., Weiskirchen S., Weiskirchen R. Cellular mechanisms of liver fibrosis. Frontiers in Pharmacology. 2021;12. 671640. doi:10.3389/fphar.2021.671640.
2. Chen L., Fu C., Zhang Q., et al. The role of CD44 in pathological angiogenesis. FASEB J. 2020;34(10):13125-13139. doi: 10.1096/fj.202000380RR.
3. Dhar D., Baglieri J., Kisseleva T., Brenner D.A. Mechanisms of liver fibrosis and its role in liver cancer. Experimental. Biology and Medicine. 2020;245:96-108. doi: 10.1177/1535370219898141.
4. Everhart J.E., Wright E.C., Goodman Z.D., et al. Prognostic value of Ishak fibrosis stage: findings from the hepatitis C antiviral long-term treatment against cirrhosis trial. Hepatology. 2010;51:585. doi: 10.1002/hep.23315
5. Gana J.C., Serrano C.A., Ling S.C. Angiogenesis and Portal-Systemic Collaterals in portal hypertension. Annals of Hepatology. 2016;15:303-13. doi: 10.5604/16652681.1198799.
6. Guerrier M., Attili F., Alpini G., Glaser S. Prolonged administration of secretin to normal rats increases biliary proliferation and secretininduced ductal secretory activity. Hepatobiliary Surg. Nutr. 2014;3:118. doi.org/10.3978/j.issn.2304-3881.2014.04.04
7. Jeong J.H., Ojha U., Lee Y.M. Pathological angiogenesis and inflammation in tissues. Arch. Pharm. Res. 2021;44(1):1-15. doi: 10.1007/s12272-020-01287-2.
8. Kisseleva T., Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 2021;18(3):151-166. doi: 10.1038/s41575-020-00372-7.
9. Lafoz E., Ruart M., Anton A., et al. The Endothelium as a Driver of Liver Fibrosis and Regeneration. Cells. 2020;9(4):929. doi: 10.3390/cells9040929.
10. Lefere S., Devisscher L., Geerts A. Angiogenesis in the progression of non-alcoholic fatty liver disease. Acta Gastroenterol. Belg. 2020;83(2):301-307.
11. Li H. Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma. Expert. Rev. Gastroenterol. Hepatol. 2021;15(3):217-233. doi: 10.1080/17474124.2021.1842732.
12. Muthiah M.D., Huang D.Q., Zhou L., Jumat N.H. et al. A murine model demonstrating reversal of structural and functional correlates of cirrhosis with progenitor cell transplantation. Sci. Rep. 2019;9. 15446. doi: 10.1038/s41598-019-51189-7.
13. Parola M., Pinzani M. Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues. Mol. Aspects. Med. 2019;65:37-55. doi: 10.1016/j.mam.2018.09.002.
14. Roehlen N., Crouchet E., Baumert T.F. Liver fibrosis: Mechanistic concepts and therapeutic perspectives. Cells. 2020;9:875. doi: 10.3390/cells9040875.
15. Shi H., Dong L., Bai Y., et al. Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats. European Journal of Pharmacology. 2009;623:119-24. doi:10.1016/j.ejphar.2009.09.026.
16. Srivastava A., Shukla V., Tiwari D., et al. Targeted therapy of chronic liver diseases with the inhibitors of angiogenesis Biomed Pharmacother. 2018;105:256-266. doi: 10.1016/j.biopha.2018.05.102.
17. Tripathi D.M., Hassan M., Siddiqui H., et al. Cirrhotic endothelial progenitor cells enhance liver angiogenesis and fibrosis and aggravate portal hypertension in bile duct-ligated cirrhotic rats. Frontiers in Physiology. 2020;11. doi: 10.3389/fphys.2020.00617.
18. Zadorozhna M., Di Gioia S., Conese M., Mangieri D. Neovascularization is a key feature of liver fibrosis progression: Anti-angiogenesis as an innovative way of liver fibrosis treatment. Molecular Biology Reports. 2020;47:2279-88. doi: 10.1007/s11033-020-05290-0.
19. Zhai M., Long J., Liu S., et al. The burden of liver cirrhosis and underlying etiologies: Results from the global burden of disease study 2017. Aging. 2021;13:279–300. doi:10.18632/aging.104127.
Review
For citations:
Lebedeva E.I. Morphometric parameters of sinusoidal capillaries, interlobular veins and interlobular arteries at different stages of experimental liver fibrosis. Journal of Anatomy and Histopathology. 2022;11(3):32-38. (In Russ.) https://doi.org/10.18499/2225-7357-2022-11-3-32-38