Effect of nerve growth factor dimeric mimetic GK-2 on microcirculation in skeletal muscle on the hind limb ischemia model in rats

The purpose of the study. In experiments on a hind limb ischemia model in rats, the effect of the TrkA-receptor agonist of the NGF 4th loop dimeric dipeptide mimetic compound GK-2 has been studied on microcirculation in ischemic skeletal muscle.

Methods. the Hind limb ischemia was caused in white male mongrel rats by the femoral artery resection. The compound GK-2 was administered intravenously (1 mg/kg/day during 14 days). Microcirculation parameters were recorded using a computer laser analyzer "LAKK-OP2". Registration was carried out simultaneously in the intact and operated limb before the operation, 1 and 14 days after it.

Results. In the conditions of the hind limb ischemia model, it was shown that the compound GK-2 almost completely restored the perfusion index and its variation coefficient in the ischemic muscle to the intact contralateral limb level by the 14th day after surgery.

Conclusion. It can be assumed that the anti-ischemic effect of the compound GK-2 is associated with the restoration of microcirculation as a result of increased neoangiogenesis.

1. Ko SH, Bandyk DF. Therapeutic angiogenesis for critical limb ischemia. Semin Vasc Surg. 2014; 27(1): 23–31. DOI: 10.1053/j.semvascsurg.2014.10.001.

2. Parfenova EV, Tkachuk VA. Therapeutic angiogenesis: advaces, problems, prospects. Cardiological bulletin. 2007;2(2(14)): 5–15. (In Russ).

3. Blais M, Lévesque P, Bellenfant S et al. Nerve growth factor, brainderived neurotrophic factor, neurotrophin-3 and glial-derived neurotrophic factor enhance angiogenesis in a tissue-engineered in vitro model. Tissue Eng Part A. 2013;19(15-16):1655–1664. DOI: 10.1089/ten.tea.2012.0745.

4. Kryzhanovskii SA, Vititnova MB. Cardiovascular effects of nerve growth factor. Human Physiology. 2011;37(3):109–128. (In Russ).

5. Raychaudhuri SK, Raychaudhuri SP, Weltman H, Farber EM. Effect of nerve growth factor on endothelial cell biology: proliferation and adherence molecule expression on human dermal microvascular endothelial cells. Arch Dermatol Res. 2001:293(6); 291–295. DOI: 10.1007/s004030100224.

6. Emanueli C, Salis MB, Pinna A et al. Nerve growth factor promotes angiogenesis and arteriogenesis in ischemic hindlimbs. Circulation. 2002;106(17):2257–2262. DOI: 10.1161/01.cir.0000033971.56802.c5.

7. Gudasheva TA, Antipova TA, Seredenin SB. Novel low-molecular-weight mimetics of the nerve growth factor. Doklady Biochemistry and Biophysics. 2010;434(1):262–265. (In Russ).

8. Gudasheva TA, Povarnina PYu, Antipova TA, Seredenin SB. A novel dimeric dipeptide mimetic of the nerve growth factor exhibits pharmacological effects upon systemic administration and has no side effects accompanying the neurotrophin treatment. Neuroscience & Medicine. 2014;5(02):101–108. DOI: 10.4236/nm.2014.52013.

9. Gudasheva TA, Antipova TA, Konstantinopolsky MA et al. Nerve growth factor novel dipeptide mimetic GK-2 selectively activates TrkA postreceptor signaling pathways and does not cause adverse effects of native neurotrophin. Doklady Biochemistry and Biophysics. 2014;456(1):88–91. (In Russ). DOI: 10.7868/S0869565214140254.

10. Kryzhanovskii SA, Antipova TA, Tsorin IB. et al. Angiogenic effects of dimeric dipeptide mimetic of loop 4 of nerve growth factor. Bulletin of Experimental Biology and Medicine. 2016;161(4):503–507. (In Russ).

11. Pekeldina ES, Ionova EO, Mirochkina IA et al. Antiischemic properties of the TrkA-receptor agonist, the nerve growth factor 4th loop mimetic. Farmakokinetica i farmacodinamica. 2018;(2):16–21. (In Russ).

12. Krupatkin AI, Sidorov VV. Funkcional'naya diagnostika sostoyaniya diagnosti sostoyaniya mikrocirkulyarno-tkanevyh sistem. Kolebaniya, informaciya, nelinejnost'. Rukovodstvo dlya vrachej. Moscow: Knizhnyj dom «Librokom»; 2014. 488 (In Russ).