Radioprotektivna zaštita akutno faznog proteina α2-makroglobulina na ćelije kosne srži pacova

Abstract

The rat acute phase protein α2-macroglobulin (α2M) plays an important role in the restoration of disrupted homeostasis by inhibiting different types of non-specific proteases and facilitating the transport of cytokines, growth factors and hormones. Previously, we observed that administration of α2M to experimental animals prior to the infliction of life- threatening trauma in the form of scalding or total-body irradiation, significantly improved their survival rates. The aim of the present work was to evaluate the radioprotective effect on blood cells of α2M that, when administered 30 min before irradiation with 6.7 Gy (LD50/30), provides 100% survival of experimental animals where in unprotected irradiated rats the said dose results in 50% lethality. We observed that rats pretreated with α2M, after an initial decline, exhibited complete recovery of the leukocyte count due to the preservation of bone marrow cells, observed as a stable mitotic index. In untreated irradiated rats the decrease of the mitotic index reflected the significant destruction of bone marrow cells that resulted in a protracted decline in the leukocyte count. We conclude that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow.

Pacovski alfa2-makroglobulin (α2M) ima važnu ulogu u uspostavljanju narušene homeostaze inhibicijom različitih tipova nespecifičnih proteaza i olakšavajući transport citokina, hormona rasta i hormona. Naša ranija istraživanja su pokazala da administracija α2M eksperimentalnim životinjama u traumama tipa opekotine ili ozračivanja celog organizma značajno povećava njihovu stopu preživljavanja. Cilj ove studije je bio izučavanje radioprotektivne uloge α2M na ćelije kosne srži. α2M je apliciran 30 minuta pre ozračivanja pacova dozom od 6.7 Gy (LD50/30) X-zraka i omogućio je 100% preživljavanje pacova za razliku od ozračenih pacova bez tretmana kod kojih je smrtnost bila 50%. Rezultati su pokazali da tretiranje životinja sa α2M, nakon inicijalnog pada, omogućavaju potpuni oporavak broja leukocita kao posledica očuvanja ćelija kosne srži, što se uočava preko stabilnog mitotskog indeksa. Kod ozračenih pacova bez tretmana signifikantno smanjenje mitotskog indeksa, kao posledica narušavanja ćelija kosne srži, rezultuje i u prolongiranom padu broja leukocita. Na osnovu ovih rezultata može se zaključiti da se radioprotektivna uloga α2M delom odvija putem citoprotekcije novih krvnih ćelija u kosnoj srži.