Avaliação de dois modelos experimentais de trombose venosa profunda: estase venosa e lesão endotelial
DOI:
https://doi.org/10.33448/rsd-v12i4.40975Palavras-chave:
Trombose venosa; Modelos animais; Cloreto férrico; Ligadura.Resumo
A trombose venosa profunda é uma importante causa de morbimortalidade no mundo, principalmente no âmbito intra-hospitalar, justificando seu tratamento e também profilaxia quando necessário. Os métodos de indução de trombose venosa profunda em animais são fundamentais para o estudo da fisiopatologia da doença, assim como para testes de drogas antitrombóticas. Os objetivos do trabalho foram avaliar e comparar dois métodos de indução de trombose venosa profunda em ratos: o modelo por estase venosa, amplamente descrito na literatura, e o modelo por lesão endotelial, com poucos estudos, principalmente em ratos. Foram usados ratos machos Wistar para indução da trombose venosa profunda. Para estase foi dissecada e ligada a veia cava inferior por 3 horas e após retirado o segmento com a veia contendo o trombo. Para o modelo de lesão endotelial, foi aplicado por 1 minuto um pedaço de papel filtro embebido em FeCl3 e avaliado o segmento após 1 hora. Em ambos os modelos foram avaliados o peso úmido e a área de oclusão. Para o peso úmido obteve-se comparando os métodos de lesão endotelial e estase respectivamente: 17,7mg (±3,0mg) vs. 2.34mg (±1,8mg) com P<0,001. Para a área de oclusão obteve-se comparando os métodos de lesão endotelial e estase respectivamente: 85,11% (±9,67%) vs. 40,83% (±33,14%), com P<0,05. Em todas as variáveis o método de lesão endotelial possuiu resultados superiores ao método de estase venosa, mostrando ser mais reprodutível.
Referências
Albadawi, H., Witting, A. A., Pershad, Y., Wallace, A., Fleck, A. R., Hoang, P., Khademhosseini, A., & Oklu, R. (2017). Animal models of venous thrombosis. Cardiovascular diagnosis and therapy, 7 (Suppl 3), S197–S206. https://doi.org/10.21037/cdt.2017.08.10
Alessio, A. M., Beltrame, M. P., Nascimento, M. C., Vicente, C. P., de Godoy, J. A., Silva, J. C., Bittar, L. F., Lorand-Metze, I., de Paula, E. V., & Annichino-Bizzacchi, J. M. (2013). Circulating progenitor and mature endothelial cells in deep vein thrombosis. International journal of medical sciences, 10(12), 1746–1754. https://doi.org/10.7150/ijms.6887
Barr, J. D., Chauhan, A. K., Schaeffer, G. V., Hansen, J. K., & Motto, D. G. (2013). Red blood cells mediate the onset of thrombosis in the ferric chloride murine model. Blood, 121(18), 3733–3741. https://doi.org/10.1182/blood-2012-11-468983
Brill, A., Fuchs, T. A., Chauhan, A. K., Yang, J. J., De Meyer, S. F., Köllnberger, M., Wakefield, T. W., Lämmle, B., Massberg, S., & Wagner, D. D. (2011). von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models. Blood, 117(4), 1400–1407. https://doi.org/10.1182/blood-2010-05-287623.
Ciciliano, J. C., Sakurai, Y., Myers, D. R., Fay, M. E., Hechler, B., Meeks, S., Li, R., Dixon, J. B., Lyon, L. A., Gachet, C., & Lam, W. A. (2015). Resolving the multifaceted mechanisms of the ferric chloride thrombosis model using an interdisciplinary microfluidic approach. Blood, 126(6), 817–824. https://doi.org/10.1182/blood-2015-02-628594
Cohoon, K. P., Leibson, C. L., Ransom, J. E., Ashrani, A. A., Petterson, T. M., Long, K. H., Bailey, K. R., & Heit, J. A. (2015). Costs of venous thromboembolism associated with hospitalization for medical illness. The American journal of managed care, 21(4), e255–e263.
Couture, L., Richer, L. P., Cadieux, C., Thomson, C. M., & Hossain, S. M. (2011). An optimized method to assess in vivo efficacy of antithrombotic drugs using optical coherence tomography and a modified Doppler flow system. Journal of pharmacological and toxicological methods, 64(3), 264–268. https://doi.org/10.1016/j.vascn.2011.09.001
Cui, G., Shan, L., Guo, L., Keung Chu, I., Li, G., Quan, Q., Zhao, Y., Meng Chong, C., Zhang, Z., Yu, P., Hoi, M. P., Sun, Y., Wang, Y., & Lee, S. M. (2015). Corrigendum: Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy. Scientific reports, 5, 13509. https://doi.org/10.1038/srep13509
Dai, B., Li, L., Li, Q., Song, X., Chen, D., Dai, J., Yao, Y., Yan, W., Teng, H., Yang, F., Xu, Z., & Jiang, Q. (2017). Novel microspheres reduce the formation of deep venous thrombosis and repair the vascular wall in a rat model. Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis, 28(5), 398–406. https://doi.org/10.1097/MBC.0000000000000629
Diaz, J. A., Obi, A. T., Myers, D. D., Jr, Wrobleski, S. K., Henke, P. K., Mackman, N., & Wakefield, T. W. (2012). Critical review of mouse models of venous thrombosis. Arteriosclerosis, thrombosis, and vascular biology, 32(3), 556–562. https://doi.org/10.1161/ATVBAHA.111.244608.
Diaz, J. A., Saha, P., Cooley, B., Palmer, O. R., Grover, S. P., Mackman, N., Wakefield, T. W., Henke, P. K., Smith, A., & Lal, B. K. (2019). Choosing a Mouse Model of Venous Thrombosis. Arteriosclerosis, thrombosis, and vascular biology, 39(3), 311–318. https://doi.org/10.1161/ATVBAHA.118.311818
Fernandez, M. M., Hogue, S., Preblick, R., & Kwong, W. J. (2015). Review of the cost of venous thromboembolism. Clinic Economics and outcomes research: CEOR, 7, 451–462. https://doi.org/10.2147/CEOR.S85635.
Frisbie J. H. (2005). An animal model for venous thrombosis and spontaneous pulmonary embolism. Spinal cord, 43(11), 635–639. https://doi.org/10.1038/sj.sc.3101770.
Gustafsson, D., Nyström, J., Carlsson, S., Bredberg, U., Eriksson, U., Gyzander, E., Elg, M., Antonsson, T., Hoffmann, K., Ungell, A., Sörensen, H., Någård, S., Abrahamsson, A., & Bylund, R. (2001). The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thrombosis research, 101(3), 171–181. https://doi.org/10.1016/s0049-3848(00)00399-6.
Gong, G., Qin, Y., & Huang, W. (2011). Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo. Phytomedicine: international journal of phytotherapy and phytopharmacology, 18(6), 458–463. https://doi.org/10.1016/j.phymed.2010.08.015.
Heit, J. A., Spencer, F. A., & White, R. H. (2016). The epidemiology of venous thromboembolism. Journal of thrombosis and thrombolysis, 41(1), 3–14. https://doi.org/10.1007/s11239-015-1311-6.
Henke, P. K., Varma, M. R., Moaveni, D. K., Dewyer, N. A., Moore, A. J., Lynch, E. M., Longo, C., Deatrick, C. B., Kunkel, S. L., Upchurch, G. R., Jr, & Wakefield, T. W. (2007). Fibrotic injury after experimental deep vein thrombosis is determined by the mechanism of thrombogenesis. Thrombosis and haemostasis, 98(5), 1045–1055.
Hennan, J. K., Morgan, G. A., Swillo, R. E., Antrilli, T. M., Mugford, C., Vlasuk, G. P., Gardell, S. J., & Crandall, D. L. (2008). Effect of tiplaxtinin (PAI-039), an orally bioavailable PAI-1 antagonist, in a rat model of thrombosis. Journal of thrombosis and haemostasis: JTH, 6(9), 1558–1564. https://doi.org/10.1111/j.1538-7836.2008.03063.x.
Herbert, J. M., Tissinier, A., Defreyn, G., & Maffrand, J. P. (1993). Inhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. Arteriosclerosis and thrombosis: a journal of vascular biology, 13(8), 1171–1179. https://doi.org/10.1161/01.atv.13.8.1171
Himber, J., Wohlgensinger, C., Roux, S., Damico, L. A., Fallon, J. T., Kirchhofer, D., Nemerson, Y., & Riederer, M. A. (2003). Inhibition of tissue factor limits the growth of venous thrombus in the rabbit. Journal of thrombosis and haemostasis: JTH, 1(5), 889–895. https://doi.org/10.1046/j.1538-7836.2003.00110.x.
Jagadeeswaran, P., Cooley, B. C., Gross, P. L., & Mackman, N. (2016). Animal Models of Thrombosis from Zebrafish to Nonhuman Primates: Use in the Elucidation of New Pathologic Pathways and the Development of Antithrombotic Drugs. Circulation research, 118(9), 1363–1379. https://doi.org/10.1161/CIRCRESAHA.115.306823.
Jin, Q. Q., Sun, J. H., Du, Q. X., Lu, X. J., Zhu, X. Y., Fan, H. L., Hölscher, C., & Wang, Y. Y. (2017). Integrating microRNA and messenger RNA expression profiles in a rat model of deep vein thrombosis. International journal of molecular medicine, 40(4), 1019–1028. https://doi.org/10.3892/ijmm.2017.3105
Kurz, K. D., Main, B. W., & Sandusky, G. E. (1990). Rat model of arterial thrombosis induced by ferric chloride. Thrombosis research, 60(4), 269–280. https://doi.org/10.1016/0049-3848(90)90106-m.
Li, H., Zhang, B., Lu, S., Ji, D. G., Ding, M., Ye, Y. S., & Sun, D. J. (2019). siRNA-mediated silencing of PAI-1 gene acts as a promoter over the recanalization of endothelial progenitor cells in rats with venous thrombosis. Journal of cellular physiology, 234(11), 19921–19932. https://doi.org/10.1002/jcp.28590
Liu, H., Li, P., Lin, J., Chen, W., Guo, H., Lin, J., Liu, J., Lu, Z., Yao, X., Chen, Y., & Lin, B. (2019). Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway. Journal of ethnopharmacology, 241, 111975. https://doi.org/10.1016/j.jep.2019.111975.
Myers, D. D., Jr, Henke, P. K., Wrobleski, S. K., Hawley, A. E., Farris, D. M., Chapman, A. M., Knipp, B. S., Thanaporn, P., Schaub, R. G., Greenfield, L. J., & Wakefield, T. W. (2002). P-selectin inhibition enhances thrombus resolution and decreases vein wall fibrosis in a rat model. Journal of vascular surgery, 36(5), 928–938. https://doi.org/10.1067/mva.2002.128636.
Nakata, N., & Kira, Y. (2016). Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model. Annals of vascular diseases, 9(2), 95–101. https://doi.org/10.3400/avd.oa.16-00009.
Pazzini, C., Marcato, P. D., Prado, L. B., Alessio, A. M., Höehr, N. F., Montalvão, S., Paixão, D., Durán, N., & Annichino-Bizzacchi, J. M. (2015). Polymeric Nanoparticles of Enoxaparin as a Delivery System: In Vivo Evaluation in Normal Rats and in a Venous Thrombosis Rat Model. Journal of nanoscience and nanotechnology, 15(7), 4837–4843. https://doi.org/10.1166/jnn.2015.9816
Prado, L. B., Huber, S. C., Barnabé, A., Bassora, F. D. S., Paixão, D. S., Duran, N., Annichino-Bizzacchi, J. M. (2017) Characterization of PCL and Chitosan Nanoparticles as Carriers of Enoxaparin and Its Antithrombotic Effect in Animal Models of Venous Thrombosis. Journal of Nanotechnology, 1-7, https://doi.org/10.1155/2017/4925495
Parry, T. J., Huang, Z., Chen, C., Connelly, M. A., Perzborn, E., Andrade-Gordon, P., & Damiano, B. P. (2011). Arterial antithrombotic activity of rivaroxaban, an orally active factor Xa inhibitor, in a rat electrolytic carotid artery injury model of thrombosis. Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis, 22(8), 720–726. https://doi.org/10.1097/MBC.0b013e32834cb30e
Peternel, L., Drevensek, G., Cerne, M., Stalc, A., Stegnar, M., & Budihna, M. V. (2005). Evaluation of two experimental venous thrombosis models in the rat. Thrombosis research, 115(6), 527–534. https://doi.org/10.1016/j.thromres.2004.10.007.
Reyers, I., Mussoni, L., Donati, M. B., & de Gaetano, G. (1980). Failure of aspirin at different doses to modify experimental thrombosis in rats. Thrombosis research, 18(5), 669–674. https://doi.org/10.1016/0049-3848(80)90221-2.
Saitoh, M., Kaku, S., Funatsu, T., Koshio, H., Ishihara, T., Hirayama, F., Kawasaki, T., Sasamata, M. (2007). Comparison of YM50, an Oral, Direct Factor Xa Inhibitor, with Other Antithrombotic Agents in Rodent Venous and Arterial Thrombosis Models. Blood, 110(11):3155. https://doi.org/10.1182/blood.V110.11.3155.3155
Schoenwaelder, S. M., & Jackson, S. P. (2015). Ferric chloride thrombosis model: unraveling the vascular effects of a highly corrosive oxidant. Blood, 126(24): 2652-2653. https://doi.org/10.1182/blood-2015-09-668384.
Sood, V., Luke, C., Miller, E., Mitsuya, M., Upchurch, G. R., Jr, Wakefield, T. W., Myers, D. D., & Henke, P. K. (2010). Vein wall remodeling after deep vein thrombosis: differential effects of low molecular weight heparin and doxycycline. Annals of vascular surgery, 24(2), 233–241. https://doi.org/10.1016/j.avsg.2009.11.002
Tien, A. J., Chueh, T. H., Hsia, C. P., & Chien, C. T. (2016). Monascus Adlay and Monacolin K Attenuates Arterial Thrombosis in Rats through the Inhibition of ICAM-1 and Oxidative Stress. Kidney & blood pressure research, 41(6), 815–827. https://doi.org/10.1159/000452584
van Giezen, J. J., Berntsson, P., Zachrisson, H., & Björkman, J. A. (2009). Comparison of ticagrelor and thienopyridine P2Y (12) binding characteristics and antithrombotic and bleeding effects in rat and dog models of thrombosis/hemostasis. Thrombosis research, 124(5), 565–571. https://doi.org/10.1016/j.thromres.2009.06.029.
von Brühl, M. L., Stark, K., Steinhart, A., Chandraratne, S., Konrad, I., Lorenz, M., Khandoga, A., Tirniceriu, A., Coletti, R., Köllnberger, M., Byrne, R. A., Laitinen, I., Walch, A., Brill, A., Pfeiler, S., Manukyan, D., Braun, S., Lange, P., Riegger, J., Ware, J., Massberg, S. (2012). Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. The Journal of experimental medicine, 209(4), 819–835. https://doi.org/10.1084/jem.20112322.
Xin, G., Wei, Z., Ji, C., Zheng, H., Gu, J., Ma, L., Huang, W., Morris-Natschke, S. L., Yeh, J. L., Zhang, R., Qin, C., Wen, L., Xing, Z., Cao, Y., Xia, Q., Li, K., Niu, H., Lee, K. H., & Huang, W. (2017). Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release. Free radical biology & medicine, 108, 247–257. https://doi.org/10.1016/j.freeradbiomed.2017.02.018.
Wakefield, T. W., Wrobleski, S. K., Sarpa, M. S., Taylor, F. B., Jr, Esmon, C. T., Cheng, A., & Greenfield, L. J. (1991). Deep venous thrombosis in the baboon: an experimental model. Journal of vascular surgery, 14(5), 588–598. https://doi.org/10.1067/mva.1991.32030.
Wang, X., Cheng, Q., Xu, L., Feuerstein, G. Z., Hsu, M. Y., Smith, P. L., Seiffert, D. A., Schumacher, W. A., Ogletree, M. L., & Gailani, D. (2005). Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice. Journal of thrombosis and haemostasis: JTH, 3(4), 695–702. https://doi.org/10.1111/j.1538-7836.2005.01236.x.
Wang, X., Smith, P. L., Hsu, M. Y., Ogletree, M. L., & Schumacher, W. A. (2006). Murine model of ferric chloride-induced vena cava thrombosis: evidence for effect of potato carboxypeptidase inhibitor. Journal of thrombosis and haemostasis: JTH, 4(2), 403–410. https://doi.org/10.1111/j.1538-7836.2006.01703.x.
Wong, P. C., Watson, C. A., Crain, J. E., Luettgen, J. M., Ogletree, M. L., Wexler, R. R., Lam, P. Y. S., Pinto, D. J., Knabb, R. M. (2006). Effects of the Factor Xa Inhibitor Apixaban on Venous Thrombosis and Hemostasis in Rabbits. Blood. 108 (11): 917. https://doi.org/10.1182/blood.V108.11.917.917.
Wong, P. C., Crain, E. J., Xin, B., Wexler, R. R., Lam, P. Y., Pinto, D. J., Luettgen, J. M., & Knabb, R. M. (2008). Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. Journal of thrombosis and haemostasis: JTH, 6(5), 820–829. https://doi.org/10.1111/j.1538-7836.2008.02939.x.
Zhou, J., May, L., Liao, P., Gross, P. L., & Weitz, J. I. (2009). Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats. Arteriosclerosis, thrombosis, and vascular biology, 29(6), 863–869. https://doi.org/10.1161/ATVBAHA.109.185678.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Copyright (c) 2023 Andrezza Janine de Almeida Santos; Carlos Eduardo Rodrigues Lopes; Luiz Eduardo Alessio Junior; Neiva Pereira Paim; Keila Fernanda da Cruz Souza Pinto; Rodolfo Cassimiro Araújo Berber; Aline Morandi Alessio
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Autores que publicam nesta revista concordam com os seguintes termos:
1) Autores mantém os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.
2) Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capítulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.
3) Autores têm permissão e são estimulados a publicar e distribuir seu trabalho online (ex.: em repositórios institucionais ou na sua página pessoal) a qualquer ponto antes ou durante o processo editorial, já que isso pode gerar alterações produtivas, bem como aumentar o impacto e a citação do trabalho publicado.