.ə. ɀɚɧɚɟɜɚ, Ɍ.ȼ. Ⱥɥɟɤɫɟɟɧɤɨ, Ɍ.Ⱥ. Ʉɨɪɨɥɟɧɤɨ ɋ ɂ ɆȿɌȺɋɌȺɁɂɊɈȼȺɇɂɂ ɈɉɍɏɈɅȿɃ
advertisement
ɍȾɄ 616-006:577.156.152.344 ɋ.ə. ɀɚɧɚɟɜɚ, Ɍ.ȼ. Ⱥɥɟɤɫɟɟɧɤɨ, Ɍ.Ⱥ. Ʉɨɪɨɥɟɧɤɨ ɊɈɅɖ ɋɌɂɆɍɅəɐɂɂ ɂ ȾȿɉɊȿɋɋɂɂ ɆȺɄɊɈɎȺȽɈȼ ȼ ɊȺɁȼɂɌɂɂ ɂ ɆȿɌȺɋɌȺɁɂɊɈȼȺɇɂɂ ɈɉɍɏɈɅȿɃ Ƚɍ ɇɂɂ ɮɢɡɢɨɥɨɝɢɢ ɋɈ ɊȺɆɇ, ɇɨɜɨɫɢɛɢɪɫɤ ɉɪɟɞɫɬɚɜɥɟɧɵ ɫɨɜɪɟɦɟɧɧɵɟ ɞɚɧɧɵɟ ɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɢ ɨɩɭɯɨɥɢ ɢ ɦɚɤɪɨɮɚɝɨɜ; ɨɛɫɭɠɞɚɟɬɫɹ ɞɜɨɣɫɬɜɟɧɧɨɫɬɶ ɜɡɚɢɦɨɨɬɧɨɲɟɧɢɣ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɵ, ɜ ɱɚɫɬɧɨɫɬɢ, ɟɟ ɤɥɟɬɨɱɧɨɝɨ ɧɟɫɩɟɰɢɮɢɱɟɫɤɨɝɨ ɡɜɟɧɚ ɢ ɨɩɭɯɨɥɢ. ɉɪɢɜɨɞɹɬɫɹ ɫɨɛɫɬɜɟɧɧɵɟ ɢ ɥɢɬɟɪɚɬɭɪɧɵɟ ɞɚɧɧɵɟ, ɩɨɤɚɡɵɜɚɸɳɢɟ, ɱɬɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɨɩɭɯɨɥɢ ɢ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɵ ɧɟ ɜɫɟɝɞɚ ɧɨɫɢɬ ɚɧɬɚɝɨɧɢɫɬɢɱɟɫɤɢɣ ɯɚɪɚɤɬɟɪ, ɩɪɢ ɨɩɪɟɞɟɥɟɧɧɵɯ ɭɫɥɨɜɢɹɯ ɦɚɤɪɨɮɚɝɢ ɦɨɝɭɬ ɧɟ ɬɨɥɶɤɨ ɭɧɢɱɬɨɠɚɬɶ ɨɩɭɯɨɥɟɜɵɟ ɤɥɟɬɤɢ, ɧɨ ɢ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɨɩɭɯɨɥɟɜɨɣ ɩɪɨɝɪɟɫɫɢɢ. Ɉɛɫɭɠɞɚɟɬɫɹ ɪɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɨɩɭɯɨɥɟɣ ɭ ɠɢɜɨɬɧɵɯ. Ʉɥɸɱɟɜɵɟ ɫɥɨɜɚ: ɡɥɨɤɚɱɟɫɬɜɟɧɧɵɟ ɨɩɭɯɨɥɢ, ɦɚɤɪɨɮɚɝɢ, ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɵɣ ɢɦɦɭɧɢɬɟɬ. ɇɟɫɦɨɬɪɹ ɧɚ ɡɧɚɱɢɬɟɥɶɧɵɟ ɞɨɫɬɢɠɟɧɢɹ ɜ ɢɡɭɱɟɧɢɢ ɦɟɯɚɧɢɡɦɨɜ ɜɨɡɧɢɤɧɨɜɟɧɢɹ ɢ ɪɚɡɜɢɬɢɹ ɨɧɤɨɥɨɝɢɱɟɫɤɢɯ ɡɚɛɨɥɟɜɚɧɢɣ, ɪɚɡɪɚɛɨɬɚɧɧɵɟ ɦɟɬɨɞɵ ɥɟɱɟɧɢɹ ɜ ɨɬɧɨɲɟɧɢɢ ɦɧɨɝɢɯ ɜɢɞɨɜ ɨɩɭɯɨɥɟɣ ɜɫɟ ɟɳɟ ɨɫɬɚɸɬɫɹ ɧɟɭɞɨɜɥɟɬɜɨɪɢɬɟɥɶɧɵɦɢ. Ɉɫɧɨɜɧɵɦɢ ɩɪɢɱɢɧɚɦɢ, ɩɪɢɜɨɞɹɳɢɦɢ ɤ ɜɨɡɨɛɧɨɜɥɟɧɢɸ ɨɩɭɯɨɥɟɜɨɝɨ ɩɪɨɰɟɫɫɚ ɞɚɠɟ ɩɨɫɥɟ ɡɧɚɱɢɬɟɥɶɧɨɣ ɪɟɞɭɤɰɢɢ ɨɩɭɯɨɥɟɜɨɣ ɦɚɫɫɵ ɩɨɫɥɟ ɥɟɱɟɧɢɹ, ɹɜɥɹɸɬɫɹ ɜɵɫɨɤɚɹ ɝɟɬɟɪɨɝɟɧɧɨɫɬɶ ɩɨɩɭɥɹɰɢɢ ɧɟɨɩɥɚɫɬɢɱɟɫɤɢɯ ɤɥɟɬɨɤ, ɢɯ ɝɟɧɟɬɢɱɟɫɤɚɹ ɧɟɫɬɚɛɢɥɶɧɨɫɬɶ, ɫɟɥɟɤɰɢɹ ɜ ɯɨɞɟ ɯɢɦɢɨɢɥɢ ɥɭɱɟɜɨɣ ɬɟɪɚɩɢɢ ɪɟɡɢɫɬɟɧɬɧɵɯ ɤ ɞɚɧɧɨɦɭ ɜɢɞɭ ɬɟɪɚɩɢɢ ɤɥɨɧɨɜ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ, ɷɬɢ ɠɟ ɮɚɤɬɨɪɵ ɫɩɨɫɨɛɫɬɜɭɸɬ ɞɚɥɶɧɟɣɲɟɣ ɩɪɨɝɪɟɫɫɢɢ ɨɩɭɯɨɥɟɣ [1]. ȼ ɫɜɹɡɢ ɫ ɷɬɢɦ ɜɨ ɜɫɟɦ ɦɢɪɟ ɢɧɬɟɧɫɢɜɧɨ ɪɚɡɪɚɛɚɬɵɜɚɸɬɫɹ ɧɨɜɵɟ ɩɨɞɯɨɞɵ ɤ ɥɟɱɟɧɢɸ ɡɥɨɤɚɱɟɫɬɜɟɧɧɵɯ ɨɩɭɯɨɥɟɣ, ɜ ɱɚɫɬɧɨɫɬɢ, ɢɫɫɥɟɞɭɟɬɫɹ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɩɪɢɦɟɧɟɧɢɹ ɧɚɪɹɞɭ ɫ ɬɪɚɞɢɰɢɨɧɧɵɦɢ ɦɟɬɨɞɚɦɢ (ɯɢɪɭɪɝɢɱɟɫɤɢɣ, ɪɚɞɢɨɥɨɝɢɱɟɫɤɢɣ, ɯɢɦɢɨɬɟɪɚɩɢɹ) ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɢ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɯ ɢɦɦɭɧɨɬɟɪɚɩɟɜɬɢɱɟɫɤɢɯ ɦɟɬɨɞɨɜ [2, 3, 4, 5, 6, 7]. ɇɟɫɩɟɰɢɮɢɱɟɫɤɚɹ ɢɦɦɭɧɨɬɟɪɚɩɢɹ ɨɫɧɨɜɚɧɚ ɧɚ ɩɪɢɦɟɧɟɧɢɢ ɰɢɬɨɤɢɧɨɜ ɢ ɛɚɤɬɟɪɢɚɥɶɧɵɯ ɚɞɶɸɜɚɧɬɨɜ (Ȼɐɀ, ɦɭɪɚɦɢɥ-ɞɢɩɟɩɬɢɞ, ɤɨɦɩɨɧɟɧɬɵ ɤɥɟɬɨɱɧɵɯ ɫɬɟɧɨɤ ɛɚɤɬɟɪɢɣ, ɷɧɞɨɬɨɤɫɢɧ, ɰɢɬɨɤɢɧɵ), ɧɟɫɩɟɰɢɮɢɱɟɫɤɢ ɚɤɬɢɜɢɪɭɸɳɢɯ ɨɛɳɢɟ ɢɦɦɭɧɧɵɟ ɪɟɚɤɰɢɢ ɩɭɬɟɦ ɫɬɢɦɭɥɹɰɢɢ ɦɚɤɪɨɮɚɝɨɜ, NK ɢ Ɍ-ɤɥɟɬɨɤ [2, 3]. ɇɚɢɛɨɥɟɟ ɢɡɭɱɟɧɧɵɦɢ ɢ ɲɢɪɨɤɨ ɩɪɢɦɟɧɹɟɦɵɦɢ ɩɪɟɩɚɪɚɬɚɦɢ ɢɡ ɷɬɨɣ ɝɪɭɩɩɵ ɹɜɥɹɸɬɫɹ ɬɭɛɟɪɤɭɥɟɡɧɚɹ ɜɚɤɰɢɧɚ Ȼɐɀ ɢ ɰɢɬɨɤɢɧɵ, ɡɧɚɱɢɬɟɥɶɧɨɟ ɜɧɢ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „. ɦɚɧɢɟ ɭɞɟɥɹɟɬɫɹ ɬɚɤɠɟ ɢɡɭɱɟɧɢɸ ɜɨɡɦɨɠɧɨɫɬɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɜɢɞɟ ɦɨɧɨ- ɢ ɫɨɱɟɬɚɧɧɨɣ ɬɟɪɚɩɢɢ ɡɥɨɤɚɱɟɫɬɜɟɧɧɵɯ ɨɩɭɯɨɥɟɣ ɜ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɣ ɨɧɤɨɥɨɝɢɢ ɢ ɜ ɤɥɢɧɢɤɟ ɩɨɥɢɝɥɢɤɚɧɨɜ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɤɥɟɬɨɱɧɵɯ ɫɬɟɧɨɤ ɞɪɨɠɠɟɣ, ɛɚɤɬɟɪɢɣ, ɝɪɢɛɨɜ ɢ ɪɚɫɬɟɧɢɣ [2, 3, 4, 6, 7]. ɉɨɤɚɡɚɧɚ ɫɩɨɫɨɛɧɨɫɬɶ ɩɨɥɢɫɚɯɚɪɢɞɨɜ ɤɥɟɬɨɱɧɵɯ ɫɬɟɧɨɤ ɞɪɨɠɠɟɣ ɢ ɝɪɢɛɨɜ ɫɨ ɫɬɪɭɤɬɭɪɨɣ ȕ-1,3;1,6- ɢ ȕ-1,3;1,4-ɝɥɢɤɚɧɨɜ ɫɬɢɦɭɥɢɪɨɜɚɬɶ ɰɢɬɨɬɨɤɫɢɱɟɫɤɭɸ ɚɤɬɢɜɧɨɫɬɶ ɦɨɧɨɰɢɬɨɜ, ɦɚɤɪɨɮɚɝɨɜ ɢ NK-ɤɥɟɬɨɤ, ɭɫɢɥɢɜɚɬɶ ɫɟɤɪɟɰɢɸ ɦɚɤɪɨɮɚɝɚɦɢ ɰɢɬɨɥɢɬɢɱɟɫɤɢɯ ɢ ɰɢɬɨɫɬɚɬɢɱɟɫɤɢɯ ɮɚɤɬɨɪɨɜ, ɜ ɬɨɦ ɱɢɫɥɟ ɰɢɬɨɤɢɧɨɜ, ɩɪɨɬɟɨɥɢɬɢɱɟɫɤɢɯ ɮɟɪɦɟɧɬɨɜ, ɨɤɢɫɢ ɚɡɨɬɚ [6, 7]. ɂɧɬɟɪɟɫ ɤ ɪɚɫɬɜɨɪɢɦɵɦ ɝɥɢɤɚɧɚɦ ɨɛɭɫɥɨɜɥɟɧ ɢɯ ɦɟɧɶɲɟɣ ɬɨɤɫɢɱɧɨɫɬɶɸ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɪɟɤɨɦɛɢɧɚɧɬɧɵɦɢ ɰɢɬɨɤɢɧɚɦɢ, ɞɥɹ ɤɨɬɨɪɵɯ ɧɚɥɢɱɢɟ ɩɨɛɨɱɧɵɯ ɬɨɤɫɢɱɟɫɤɢɯ ɷɮɮɟɤɬɨɜ ɹɜɥɹɟɬɫɹ ɫɭɳɟɫɬɜɟɧɧɵɦ ɨɝɪɚɧɢɱɟɧɢɟɦ ɢɯ ɩɪɢɦɟɧɟɧɢɹ [6, 7]. ɉɨɥɚɝɚɸɬ, ɱɬɨ ɬɨɱɤɨɣ ɩɪɢɥɨɠɟɧɢɹ ɛɨɥɶɲɢɧɫɬɜɚ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɯ ɢɦɦɭɧɨɫɬɢɦɭɥɹɬɨɪɨɜ ɹɜɥɹɸɬɫɹ, ɝɥɚɜɧɵɦ ɨɛɪɚɡɨɦ, ɦɚɤɪɨɮɚɝɢ. Ɇɚɤɪɨɮɚɝɚɦ ɧɚɪɹɞɭ ɫ ɟɫɬɟɫɬɜɟɧɧɵɦɢ ɤɢɥɥɟɪɧɵɦɢ ɤɥɟɬɤɚɦɢ, ɫɩɟɰɢɮɢɱɟɫɤɢɦɢ ɰɢɬɨɬɨɤɫɢɱɟɫɤɢɦɢ ɤɥɟɬɤɚɦɢ, ɧɟɣɬɪɨɮɢɥɚɦɢ, ɷɨɡɢɧɨɮɢɥɚɦɢ ɢ ɞɪ. ɤɥɟɬɤɚɦɢ, ɨɛɥɚɞɚɸɳɢɦɢ ɫɩɟɰɢɮɢɱɟɫɤɢɦɢ ɢ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɦɢ ɰɢɬɨɬɨɤɫɢɱɟɫɤɢɦɢ ɷɮɮɟɤɬɚɦɢ, ɨɬɜɨɞɢɬɫɹ ɰɟɧɬɪɚɥɶɧɚɹ ɪɨɥɶ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɝɨ ɨɬɜɟɬɚ [2, 3, 8, 9]. Ɇɚɤɪɨɮɚɝɢ ɹɜɥɹɸɬɫɹ ɝɥɚɜɧɵɦ ɡɜɟɧɨɦ ɧɟɫɩɟɰɢɮɢɱɟɫɤɨɝɨ ɢɦɦɭɧɢɬɟɬɚ, ɚ ɬɚɤɠɟ, ɩɪɟɡɟɧɬɢɪɭɹ ɚɧɬɢɝɟɧɵ ɢɦɦɭɧɨɤɨɦɩɟɬɟɧɬɧɵɦ ɤɥɟɬɤɚɦ, ɡɚɧɢɦɚɸɬ ɜɚɠɧɨɟ ɦɟɫɬɨ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɫɩɟɰɢɮɢ121 ɀɚɧɚɟɜɚ ɋ.ə. Ɋɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɨɩɭɯɨɥɟɣ / ɫ. 121-126 ɱɟɫɤɨɝɨ ɢɦɦɭɧɧɨɝɨ ɨɬɜɟɬɚ. ɂɦ ɩɪɢɧɚɞɥɟɠɢɬ ɤɥɸɱɟɜɚɹ ɪɨɥɶ ɜ ɪɚɫɩɨɡɧɚɜɚɧɢɢ ɱɭɠɟɪɨɞɧɵɯ ɛɟɥɤɨɜ, ɜ ɱɚɫɬɧɨɫɬɢ, ɢɡɦɟɧɟɧɧɵɯ ɩɪɢ ɨɩɭɯɨɥɟɜɨɣ ɬɪɚɧɫɮɨɪɦɚɰɢɢ ɤɥɟɬɨɤ, ɜ ɭɞɚɥɟɧɢɢ ɨɬɠɢɜɲɢɯ ɢ ɩɨɜɪɟɠɞɟɧɧɵɯ ɤɥɟɬɨɤ, ɨɧɢ ɩɪɨɞɭɰɢɪɭɸɬ ɲɢɪɨɤɢɣ ɫɩɟɤɬɪ ɰɢɬɨɤɢɧɨɜ ɢ ɞɪɭɝɢɯ ɜɟɳɟɫɬɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ɪɚɡɥɢɱɧɵɟ ɷɬɚɩɵ ɢɦɦɭɧɧɵɯ ɪɟɚɤɰɢɣ [2, 3, 8, 9]. ɋɩɨɫɨɛɧɨɫɬɶ ɦɚɤɪɨɮɚɝɨɜ ɤ ɪɚɫɩɨɡɧɚɜɚɧɢɸ ɢ ɭɧɢɱɬɨɠɟɧɢɸ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ in vivo ɢ in vitro ɛɵɥɚ ɨɛɧɚɪɭɠɟɧɚ ɟɳɟ ɜ 60-ɯ ɝɨɞɚɯ [9]. ɉɨɤɚɡɚɧɨ, ɱɬɨ in vitro ɞɨɛɚɜɥɟɧɢɟ ɚɤɬɢɜɢɪɨɜɚɧɧɵɯ ɦɚɤɪɨɮɚɝɨɜ ɜ ɤɭɥɶɬɭɪɭ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ ɜɵɡɵɜɚɟɬ ɝɢɛɟɥɶ ɤɥɟɬɨɤ ɨɩɭɯɨɥɢ, ɚ in vivo ɩɪɢ ɜɧɭɬɪɢɜɟɧɧɨɦ ɜɜɟɞɟɧɢɢ ɚɤɬɢɜɢɪɨɜɚɧɧɵɟ ɦɚɤɪɨɮɚɝɢ ɢɧɝɢɛɢɪɭɸɬ ɪɨɫɬ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɧɟɤɨɬɨɪɵɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɨɩɭɯɨɥɟɣ. Ⱥɤɬɢɜɢɪɨɜɚɧɧɵɟ ɫɩɥɟɧɨɰɢɬɵ ɠɢɜɨɬɧɵɯ-ɨɩɭɯɨɥɟɧɨɫɢɬɟɥɟɣ ɭɱɚɫɬɜɭɸɬ ɜ ɩɪɟɞɭɩɪɟɠɞɟɧɢɢ ɪɚɡɜɢɬɢɹ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɦɟɬɚɫɬɚɡɨɜ [5, 8, 9, 10]. ɇɚ ɦɨɞɟɥɢ ɩɟɪɟɜɢɜɚɟɦɨɣ ɦɵɲɢɧɨɣ ɚɞɟɧɨɤɚɪɰɢɧɨɦɵ ɤɢɲɟɱɧɢɤɚ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɩɪɢ ɢɦɦɭɧɢɡɚɰɢɢ ɦɵɲɟɣ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ ɢɦɟɧɧɨ ɦɚɤɪɨɮɚɝɢ ɹɜɥɹɸɬɫɹ ɝɥɚɜɧɵɦ ɷɮɮɟɤɬɨɪɧɵɦ ɰɢɬɨɬɨɤɫɢɱɟɫɤɢɦ ɡɜɟɧɨɦ, ɨɬɜɟɬɫɬɜɟɧɧɵɦ ɡɚ ɭɧɢɱɬɨɠɟɧɢɟ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ [10]. ɉɪɟɞɩɨɥɚɝɚɸɬ, ɱɬɨ ɦɚɤɪɨɮɚɝɢ, NKɤɢɥɥɟɪɵ ɢ ɰɢɬɨɬɨɤɫɢɱɟɫɤɢɟ Ɍ-ɥɢɦɮɨɰɢɬɵ, ɨɫɭɳɟɫɬɜɥɹɹ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɵɣ ɧɚɞɡɨɪ, ɭɧɢɱɬɨɠɚɸɬ ɦɧɨɝɢɟ ɨɩɭɯɨɥɟɜɵɟ ɤɥɟɬɤɢ in situ, ɪɟɚɝɢɪɭɹ ɧɚ ɩɨɹɜɥɟɧɢɟ ɜ ɨɪɝɚɧɢɡɦɟ, ɜɨɡɦɨɠɧɨ, ɞɚɠɟ ɟɞɢɧɢɱɧɵɯ ɬɪɚɧɫɮɨɪɦɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ. ɉɪɹɦɨɟ ɰɢɬɨɬɨɤɫɢɱɟɫɤɨɟ ɞɟɣɫɬɜɢɟ ɦɚɤɪɨɮɚɝɨɜ ɧɚ ɨɩɭɯɨɥɟɜɵɟ ɤɥɟɬɤɢ, ɤɚɤ ɩɨɥɚɝɚɸɬ, ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ, ɝɥɚɜɧɵɦ ɨɛɪɚɡɨɦ, ɛɥɚɝɨɞɚɪɹ ɫɟɤɪɟɰɢɢ ɢɦɢ ɬɨɤɫɢɱɧɵɯ ɞɥɹ ɨɩɭɯɨɥɢ ɫɨɟɞɢɧɟɧɢɣ — ɚɤɬɢɜɧɵɯ ɮɨɪɦ ɤɢɫɥɨɪɨɞɚ, ɨɤɢɫɢ ɚɡɨɬɚ, ɥɢɡɨɫɨɦɚɥɶɧɵɯ ɮɟɪɦɟɧɬɨɜ, ɮɚɤɬɨɪɚ ɧɟɤɪɨɡɚ ɨɩɭɯɨɥɟɣ [5, 8]. ɋ ɞɪɭɝɨɣ ɫɬɨɪɨɧɵ, ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɦɟɯɚɧɢɡɦɨɜ ɨɩɭɯɨɥɟɜɨɝɨ ɪɨɫɬɚ ɧɚ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɦɨɞɟɥɹɯ ɢ ɭ ɱɟɥɨɜɟɤɚ ɩɨɤɚɡɚɥɢ, ɱɬɨ ɤɥɟɬɤɢ ɫɢɫɬɟɦɵ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɮɚɝɨɰɢɬɨɜ, ɜ ɱɚɫɬɧɨɫɬɢ, ɦɚɤɪɨɮɚɝɢ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɨɩɭɯɨɥɶɸ, ɧɟ ɬɨɥɶɤɨ ɭɧɢɱɬɨɠɚɸɬ ɤɥɟɬɤɢ ɪɚɫɬɭɳɟɣ ɨɩɭɯɨɥɢ, ɧɨ ɢ ɩɪɢ ɨɩɪɟɞɟɥɟɧɧɵɯ ɭɫɥɨɜɢɹɯ ɦɨɝɭɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɟɟ ɪɨɫɬɭ ɢ ɩɪɨɝɪɟɫɫɢɢ, ɫɬɢɦɭɥɢɪɭɸɬ ɚɧɝɢɨɝɟɧɧɭɸ ɚɤɬɢɜɧɨɫɬɶ ɜ ɨɩɭɯɨɥɢ ɢ ɟɟ ɦɟɬɚɫɬɚɡɚɯ [8, 11]. Ɍɤɚɧɢ ɩɟɪɜɢɱɧɵɯ ɨɩɭɯɨɥɟɣ, ɡɨɧɵ ɢɧɜɚɡɢɢ ɨɩɭɯɨɥɟɣ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɧɚ ɧɚɱɚɥɶɧɵɯ ɷɬɚɩɚɯ ɢɯ ɪɚɡɜɢɬɢɹ ɦɚɫɫɢɜɧɨ ɢɧɮɢɥɶɬɪɢɪɨɜɚɧɵ ɦɚɤɪɨɮɚɝɚɦɢ, ɜ ɞɚɥɶɧɟɣɲɟɦ ɫ ɭɜɟɥɢɱɟɧɢɟɦ ɦɚɫɫɵ ɩɟɪɜɢɱɧɨɣ 122 ɨɩɭɯɨɥɢ ɢɥɢ ɦɟɬɚɫɬɚɬɢɱɟɫɤɢɯ ɭɡɥɨɜ ɨɬɧɨɫɢɬɟɥɶɧɨɟ ɫɨɞɟɪɠɚɧɢɟ ɦɚɤɪɨɮɚɝɨɜ ɜ ɨɩɭɯɨɥɢ ɢ ɢɯ ɬɭɦɨɪɢɰɢɞɧɚɹ ɚɤɬɢɜɧɨɫɬɶ ɫɧɢɠɚɟɬɫɹ [12, 13]. Ɉɫɧɨɜɧɨɣ ɩɪɢɱɢɧɨɣ ɦɢɝɪɚɰɢɢ ɦɨɧɨɰɢɬɨɜ ɢɡ ɤɪɨɜɢ ɜ ɬɤɚɧɶ ɨɩɭɯɨɥɢ ɫɱɢɬɚɸɬ ɪɚɡɜɢɬɢɟ ɜ ɨɩɭɯɨɥɢ ɥɨɤɚɥɶɧɵɯ ɡɨɧ ɝɢɩɨɤɫɢɢ, ɪɚɡɜɢɬɢɸ ɤɨɬɨɪɵɯ ɫɩɨɫɨɛɫɬɜɭɟɬ ɧɟɞɨɫɬɚɬɨɱɧɚɹ ɜɚɫɤɭɥɹɪɢɡɚɰɢɹ ɛɵɫɬɪɨ ɪɚɫɬɭɳɢɯ ɨɩɭɯɨɥɟɣ ɢ ɫɤɥɨɧɧɨɫɬɶ ɫɨɫɭɞɨɜ ɨɩɭɯɨɥɢ ɤ ɪɚɡɪɭɲɟɧɢɸ [8, 9]. Ɍɚɤ, ɧɚ ɩɪɢɦɟɪɟ ɪɚɤɚ ɝɪɭɞɢ, ɤɨɥɨɪɟɤɬɚɥɶɧɨɝɨ ɪɚɤɚ ɱɟɥɨɜɟɤɚ, ɚ ɬɚɤɠɟ ɪɚɡɥɢɱɧɵɯ ɜɢɞɨɜ ɨɩɭɯɨɥɟɣ ɠɢɜɨɬɧɵɯ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ ɦɚɤɪɨɮɚɝɨɜ ɜ ɨɩɭɯɨɥɢ ɩɪɹɦɨ ɩɪɨɩɨɪɰɢɨɧɚɥɶɧɨ ɩɨɤɚɡɚɬɟɥɹɦ ɨɛɳɟɣ ɝɢɩɨɤɫɢɢ [8, 9, 14]. Ɉɫɧɨɜɧɵɦ ɮɚɤɬɨɪɨɦ, ɩɪɢɜɥɟɤɚɸɳɢɦ ɦɨɧɨɰɢɬɵ ɢ ɧɟɣɬɪɨɮɢɥɵ ɢɡ ɤɪɨɜɢ ɜ ɬɤɚɧɶ ɨɩɭɯɨɥɢ, ɹɜɥɹɟɬɫɹ ɧɟɤɪɨɡ ɤɥɟɬɨɤ ɜ ɩɥɨɯɨ ɫɧɚɛɠɚɟɦɵɯ ɤɢɫɥɨɪɨɞɨɦ ɢ ɩɢɬɚɬɟɥɶɧɵɦɢ ɜɟɳɟɫɬɜɚɦɢ ɨɛɥɚɫɬɹɯ ɨɩɭɯɨɥɢ [8, 9, 14]. ɉɨɩɚɞɚɹ ɜ ɝɢɩɨɤɫɢɱɟɫɤɢɟ ɭɫɥɨɜɢɹ, ɦɚɤɪɨɮɚɝɢ ɩɪɨɞɭɰɢɪɭɸɬ ɪɚɡɥɢɱɧɵɟ ɯɟɦɨɚɬɬɪɚɤɬɚɧɬɵ — ɷɧɞɨɬɟɥɢɚɥɶɧɵɣ ɦɨɧɨɰɢɬɚɤɬɢɜɢɪɭɸɳɢɣ ɩɟɩɬɢɞ (EMAP), ɷɧɞɨɬɟɥɢɧ 2, ɫɨɫɭɞɢɫɬɨ-ɷɧɞɨɬɟɥɢɚɥɶɧɵɣ ɮɚɤɬɨɪ ɪɨɫɬɚ (VEGF), ɦɚɤɪɨɮɚɝɚɥɶɧɵɣ ɤɨɥɨɧɢɟɫɬɢɦɭɥɢɪɭɸɳɢɣ ɮɚɤɬɨɪ (M-CSF) ɢ ɞɪ., ɫɩɨɫɨɛɫɬɜɭɹ ɞɚɥɶɧɟɣɲɟɦɭ ɪɟɤɪɭɬɢɪɨɜɚɧɢɸ ɥɟɣɤɨɰɢɬɨɜ ɢ ɧɟɨɜɚɫɤɭɥɹɪɢɡɚɰɢɢ ɬɤɚɧɢ ɨɩɭɯɨɥɢ [8, 9, 15, 16]. Ɉɛɧɚɪɭɠɟɧɨ, ɱɬɨ ɭɫɢɥɟɧɧɚɹ ɷɤɫɩɪɟɫɫɢɹ MCSF, ɨɬɜɟɬɫɬɜɟɧɧɨɝɨ ɡɚ ɜɵɠɢɜɚɧɢɟ ɢ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɭ ɦɚɤɪɨɮɚɝɨɜ, ɜ ɬɤɚɧɹɯ ɪɹɞɚ ɨɩɭɯɨɥɟɣ ɱɟɥɨɜɟɤɚ ɤɨɪɪɟɥɢɪɭɟɬ ɫ ɜɵɫɨɤɢɦ ɫɨɞɟɪɠɚɧɢɟɦ ɜ ɨɩɭɯɨɥɢ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɮɚɝɨɰɢɬɨɜ ɢ ɧɢɡɤɨɣ ɩɪɨɞɨɥɠɢɬɟɥɶɧɨɫɬɶɸ ɠɢɡɧɢ [8, 9] . Ɇɚɤɪɨɮɚɝɢ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɨɩɭɯɨɥɶɸ, ɜ ɨɬɥɢɱɢɟ ɨɬ ɦɚɤɪɨɮɚɝɨɜ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɡɞɨɪɨɜɵɯ ɬɤɚɧɟɣ ɢɥɢ ɜɨɫɩɚɥɢɬɟɥɶɧɵɯ ɷɤɫɭɞɚɬɨɜ, ɯɚɪɚɤɬɟɪɢɡɭɸɬɫɹ ɫɧɢɠɟɧɧɨɣ ɫɩɨɫɨɛɧɨɫɬɶɸ ɤ ɥɢɡɢɫɭ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ in vitro, ɩɪɟɡɟɧɬɚɰɢɢ ɨɩɭɯɨɥɶ-ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɯ ɚɧɬɢɝɟɧɨɜ, ɫɧɢɠɟɧɧɨɣ ɷɤɫɩɪɟɫɫɢɟɣ ɢɦɦɭɧɨɫɬɢɦɭɥɢɪɭɸɳɢɯ ɰɢɬɨɤɢɧɨɜ [8]. ɉɨɥɚɝɚɸɬ, ɱɬɨ ɜ ɢɧɝɢɛɢɪɨɜɚɧɢɢ ɮɭɧɤɰɢɣ ɦɚɤɪɨɮɚɝɨɜ ɜ ɨɩɭɯɨɥɟɜɨɣ ɬɤɚɧɢ ɭɱɚɫɬɜɭɸɬ ɩɪɨɬɢɜɨɜɨɫɩɚɥɢɬɟɥɶɧɵɟ ɰɢɬɨɤɢɧɵ ɢ ɮɚɤɬɨɪɵ, ɜɵɪɚɛɚɬɵɜɚɟɦɵɟ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ, — IL-4, IL-10, TGF-E1, PGȿ2 [8, 14, 17]. Mantovani et al. (2002) ɩɨɤɚɡɚɥɢ, ɱɬɨ ɜɜɟɞɟɧɢɟ IL-4 ɢɥɢ IL-10 ɫɬɢɦɭɥɢɪɭɟɬ ɩɪɟɜɪɚɳɟɧɢɟ ɦɨɧɨɰɢɬɨɜ ɨɩɭɯɨɥɢ ɜ ɩɨɥɹɪɢɡɨɜɚɧɧɵɟ II ɬɢɩɚ ɢɥɢ Ɇɮ2 ɦɚɤɪɨɮɚɝɢ. Ɍɚɤɢɟ ɦɚɤɪɨɮɚɝɢ, ɜ ɨɬɥɢɱɢɟ ɨɬ ɤɥɚɫɫɢɱɟɫɤɢ ɚɤɬɢɜɢɪɨɜɚɧɧɵɯ ɦɚɤɪɨɮɚɝɨɜ I ɬɢɩɚ, ɨɛɥɚɞɚɸɬ ɫɥɚɛɨɣ ɚɧɬɢɝɟɧ-ɩɪɟɡɟɧɬɢɪɭɸɳɟɣ ɚɤɬɢɜɧɨɫɬɶɸ, ɚ ɬɚɤɠɟ ɫɟɤɪɟɬɢɪɭɸɬ ɮɚɤɬɨɪɵ, ɢɧɝɢɛɢɪɭɸɳɢɟ ɩɪɨɥɢɮɟɪɚɰɢɸ ɢ ɚɤ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „. ɀɚɧɚɟɜɚ ɋ.ə. Ɋɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɨɩɭɯɨɥɟɣ / ɫ. 121-126 ɬɢɜɧɨɫɬɶ Ɍ-ɥɢɦɮɨɰɢɬɨɜ, ɨɧɢ ɜ ɛɨɥɶɲɟɣ ɫɬɟɩɟɧɢ ɚɞɚɩɬɢɪɨɜɚɧɵ ɤ ɜɵɩɨɥɧɟɧɢɸ ɮɭɧɤɰɢɣ, ɫɜɹɡɚɧɧɵɯ ɫ ɪɟɝɟɧɟɪɚɰɢɟɣ ɢ ɪɟɦɨɞɟɥɢɪɨɜɚɧɢɟɦ ɩɨɜɪɟɠɞɟɧɧɵɯ ɬɤɚɧɟɣ, ɫɤɟɜɟɧɠɟɪ-ɪɟɚɤɰɢɣ, ɫɬɢɦɭɥɹɰɢɟɣ ɚɧɝɢɨɝɟɧɟɡɚ [18]. ɉɨɤɚɡɚɧɨ, ɱɬɨ ɫɨɜɦɟɫɬɧɨɟ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɟ in vitro ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɨɩɭɯɨɥɢ ɦɚɤɪɨɮɚɝɨɜ ɫ ɤɥɟɬɤɚɦɢ ɪɹɞɚ ɨɩɭɯɨɥɟɣ ɱɟɥɨɜɟɤɚ, ɭɫɢɥɢɜɚɟɬ ɷɤɫɩɪɟɫɫɢɸ ɤɚɤ ɜ ɦɚɤɪɨɮɚɝɚɯ, ɬɚɤ ɢ ɜ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɤɚɯ ɦɟɞɢɚɬɨɪɚ ɚɧɝɢɨɝɟɧɟɡɚ — ɢɧɬɟɪɥɟɣɤɢɧɚ 8 [8]. Ɉɛɧɚɪɭɠɟɧɚ ɩɨɡɢɬɢɜɧɚɹ ɤɨɪɪɟɥɹɰɢɹ ɦɟɠɞɭ ɤɨɥɢɱɟɫɬɜɨɦ ɦɚɤɪɨɮɚɝɨɜ ɜ ɬɤɚɧɹɯ ɪɹɞɚ ɨɩɭɯɨɥɟɣ ɱɟɥɨɜɟɤɚ ɢ ɠɢɜɨɬɧɵɯ ɫ ɤɨɧɰɟɧɬɪɚɰɢɟɣ ɦɟɞɢɚɬɨɪɨɜ ɚɧɝɢɨɝɟɧɟɡɚ — IL-8 ɢ VEGF ɢ ɤɨɥɢɱɟɫɬɜɨɦ ɤɪɨɜɟɧɨɫɧɵɯ ɫɨɫɭɞɨɜ ɜ ɨɩɭɯɨɥɢ ɢ ɧɟɝɚɬɢɜɧɚɹ — ɫ ɩɪɨɞɨɥɠɢɬɟɥɶɧɨɫɬɶɸ ɠɢɡɧɢ [8, 9, 15]. ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɩɨɥɭɱɟɧɵ ɞɚɧɧɵɟ, ɩɨɤɚɡɵɜɚɸɳɢɟ, ɱɬɨ ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɨɩɭɯɨɥɶɸ ɦɚɤɪɨɮɚɝɢ, ɜɟɪɨɹɬɧɨ, ɢɝɪɚɸɬ ɧɟɦɚɥɨɜɚɠɧɭɸ ɪɨɥɶ ɜ ɩɪɨɝɪɟɫɫɢɢ ɨɩɭɯɨɥɟɣ [8, 11, 16, 19, 20, 21]. Aharinejad S. et al (2004) ɩɨɤɚɡɚɥɢ, ɱɬɨ ɭ ɦɵɲɟɣ, ɧɨɤɚɭɬɢɪɨɜɚɧɧɵɯ ɩɨ ɝɟɧɭ M-CSF, ɫɨɞɟɪɠɚɧɢɟ ɦɚɤɪɨɮɚɝɨɜ ɜ ɨɩɭɯɨɥɢ ɦɨɥɨɱɧɨɣ ɠɟɥɟɡɵ ɡɧɚɱɢɬɟɥɶɧɨ ɧɢɠɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɦɵɲɚɦɢ ɫ ɧɨɪɦɚɥɶɧɵɦ ɭɪɨɜɧɟɦ ɷɤɫɩɪɟɫɫɢɢ M-CSF, ɭ ɧɢɯ ɩɨɡɞɧɟɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ ɩɨɹɜɥɹɸɬɫɹ ɩɪɢɡɧɚɤɢ ɢɧɜɚɡɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɨɩɭɯɨɥɢ, ɫɧɢɠɟɧɨ ɨɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɦɟɬɚɫɬɚɡɨɜ. ȼɜɟɞɟɧɢɟ ɚɧɬɢɫɦɵɫɥɨɜɨɣ ɊɇɄ, ɢɧɝɢɛɢɪɭɸɳɟɣ ɫɢɧɬɟɡ M-CSF, ɦɵɲɚɦ ɫ ɨɩɭɯɨɥɶɸ ɫɧɢɠɚɟɬ ɤɨɥɢɱɟɫɬɜɨ ɦɚɤɪɨɮɚɝɨɜ ɜ ɨɩɭɯɨɥɢ, ɬɨɪɦɨɡɢɬ ɚɧɝɢɨɝɟɧɟɡ ɢ ɪɨɫɬ ɨɩɭɯɨɥɢ [8, 19]. Ɇɚɤɪɨɮɚɝɢ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɨɩɭɯɨɥɶɸ, ɦɨɝɭɬ ɨɤɚɡɵɜɚɬɶ ɨɩɨɫɪɟɞɨɜɚɧɧɨɟ ɜɥɢɹɧɢɟ ɧɚ ɩɪɨɰɟɫɫ ɢɧɜɚɡɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɨɩɭɯɨɥɟɣ. Ɉɧɢ ɷɤɫɩɪɟɫɫɢɪɭɸɬ ɜ ɜɵɫɨɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ ɪɚɡɥɢɱɧɵɟ ɬɢɩɵ ɜɵɫɨɤɨɚɤɬɢɜɧɵɯ ɩɪɨɬɟɚɡ (ɫɟɪɢɧɨɜɵɟ, ɚɫɩɚɪɬɢɥɶɧɵɟ, ɰɢɫɬɟɢɧɨɜɵɟ, ɦɟɬɚɥɥɨɩɪɨɬɟɚɡɵ), ɫɟɤɪɟɰɢɹ ɤɨɬɨɪɵɯ ɩɪɢɜɨɞɢɬ ɤ ɞɟɫɬɪɭɤɰɢɢ ɤɨɦɩɨɧɟɧɬɨɜ ɷɤɫɬɪɚɰɟɥɥɸɥɹɪɧɨɝɨ ɦɚɬɪɢɤɫɚ ɢ ɷɧɞɨɬɟɥɢɚɥɶɧɵɯ ɛɚɪɶɟɪɨɜ ɢ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɛɥɟɝɱɚɸɬ ɩɪɟɨɞɨɥɟɧɢɟ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ ɬɤɚɧɟɜɵɯ ɛɚɪɶɟɪɨɜ [8, 21]. Ʉɪɨɦɟ ɬɨɝɨ, ɜɡɚɢɦɨɞɟɣɫɬɜɭɹ ɫ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ, ɦɚɤɪɨɮɚɝɢ ɭɫɢɥɢɜɚɸɬ ɫɢɧɬɟɡ ɢ ɫɟɤɪɟɰɢɸ ɜ ɧɢɯ ɧɟɤɨɬɨɪɵɯ ɩɪɨɬɟɚɡ. Ɍɚɤ, Grimshaw et al (2002) ɩɨɤɚɡɚɥɢ, ɱɬɨ ɫɨɜɦɟɫɬɧɨɟ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɦɚɤɪɨɮɚɝɨɜ ɫ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɷɧɞɨɬɟɥɢɧɨɜ 1 ɢ 2 — ɰɢɬɨɤɢɧɨɜ, ɜɵɪɚɛɚɬɵɜɚɟɦɵɯ ɦɚɤɪɨɮɚɝɚɦɢ ɜ ɭɫɥɨɜɢɹɯ ɝɢɩɨɤɫɢɢ, ɩɨɜɵɲɚɟɬ ɫɟɤɪɟɰɢɸ ɨɩɭɯɨɥɟɜɵɦɢ ɤɥɟɬɤɚɦɢ ɦɟɬɚɥɥɨɩɪɨɬɟɚɡ 2 ɢ 9 [16]. ȼɵɹɜɥɟɧɚ ɫɩɨɫɨɛɧɨɫɬɶ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ ɤ ɫɥɢɹɧɢɸ ɫ ɦɚɤɪɨɮɚɝɚɦɢ ɢ ɮɨɪɦɢɪɨɜɚɧɢɸ ɝɢɛɪɢɞɧɵɯ ɤɥɟɬɨɤ in vivo ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „. ɢ in vitro [20]. Ɇɚɤɪɨɮɚɝɢ, ɨɛɥɚɞɚɹ ɩɨɞɜɢɠɧɨɫɬɶɸ ɢ ɛɨɥɶɲɢɦ ɩɪɨɬɟɨɥɢɬɢɱɟɫɤɢɦ ɩɨɬɟɧɰɢɚɥɨɦ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɦɨɝɭɬ ɭɫɢɥɢɜɚɬɶ ɥɨɤɨɦɨɰɢɸ ɢ ɢɧɜɚɡɢɜɧɵɣ ɢ ɦɟɬɚɫɬɚɬɢɱɟɫɤɢɣ ɩɨɬɟɧɰɢɚɥ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ [20]. Ⱦɜɨɣɫɬɜɟɧɧɨɫɬɶɸ ɜɡɚɢɦɨɨɬɧɨɲɟɧɢɣ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɵ, ɜ ɱɚɫɬɧɨɫɬɢ, ɟɟ ɤɥɟɬɨɱɧɨɝɨ ɧɟɫɩɟɰɢɮɢɱɟɫɤɨɝɨ ɡɜɟɧɚ ɢ ɨɩɭɯɨɥɢ ɦɨɠɧɨ ɨɛɴɹɫɧɢɬɶ ɩɪɨɬɢɜɨɪɟɱɢɜɵɟ ɞɚɧɧɵɟ ɨɬɧɨɫɢɬɟɥɶɧɨ ɜɥɢɹɧɢɹ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɧɚ ɪɨɫɬ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɟɪɟɜɢɜɚɟɦɵɯ, ɢɧɞɭɰɢɪɨɜɚɧɧɵɯ ɤɚɧɰɟɪɨɝɟɧɚɦɢ ɢ ɫɩɨɧɬɚɧɧɵɯ ɨɩɭɯɨɥɟɣ [4, 6, 8, 11, 22]. Ɍɚɤ, ɟɳɟ ɜ 1962 ɝ. ɜ ɪɚɛɨɬɚɯ E.R. Fisher ɢ B. Fisher ɩɨɤɚɡɚɧɨ, ɚ ɩɨɡɠɟ ɩɨɞɬɜɟɪɠɞɟɧɨ ɞɪɭɝɢɦɢ ɚɜɬɨɪɚɦɢ, ɱɬɨ ɜɜɟɞɟɧɢɟ ɪɚɡɥɢɱɧɵɯ ɫɬɢɦɭɥɹɬɨɪɨɜ ɦɚɤɪɨɮɚɝɨɜ ɧɟ ɜɫɟɝɞɚ ɨɤɚɡɵɜɚɟɬ ɢɧɝɢɛɢɪɭɸɳɢɣ ɷɮɮɟɤɬ ɧɚ ɪɚɡɜɢɬɢɟ ɫɩɨɧɬɚɧɧɵɯ ɢ ɩɟɪɟɜɢɜɚɟɦɵɯ ɨɩɭɯɨɥɟɣ ɢ, ɧɚɩɪɨɬɢɜ, ɦɨɠɟɬ ɭɫɢɥɢɜɚɬɶ ɢɯ ɪɨɫɬ [4, 6, 8, 11]. Ɉɬɧɨɫɢɬɟɥɶɧɨ ɜɥɢɹɧɢɹ ɧɚ ɩɪɨɰɟɫɫ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɞɚɧɧɵɟ ɬɚɤɠɟ ɩɪɨɬɢɜɨɪɟɱɢɜɵ: ɧɚɪɹɞɭ ɫ ɫɨɨɛɳɟɧɢɹɦɢ ɨ ɬɨɦ, ɱɬɨ ɫɬɢɦɭɥɹɰɢɹ ɦɚɤɪɨɮɚɝɨɜ ɩɨɞɚɜɥɹɟɬ ɪɚɡɜɢɬɢɟ ɦɟɬɚɫɬɚɡɨɜ [10, 23, 24, 25, 26, 27], ɨɩɭɛɥɢɤɨɜɚɧɨ ɧɟɦɚɥɨ ɫɨɨɛɳɟɧɢɣ, ɩɨɤɚɡɵɜɚɸɳɢɯ, ɱɬɨ ɨɧɚ ɦɨɠɟɬ ɩɪɢɜɨɞɢɬɶ ɤ ɢɧɬɟɧɫɢɮɢɤɚɰɢɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ — ɭɜɟɥɢɱɟɧɢɸ ɤɨɥɢɱɟɫɬɜɚ ɦɟɬɚɫɬɚɬɢɱɟɫɤɢɯ ɭɡɥɨɜ ɢ ɫɤɨɪɨɫɬɢ ɢɯ ɪɨɫɬɚ [4, 8, 11, 28, 29]. Ⱦɟɩɪɟɫɫɢɹ ɦɚɤɪɨɮɚɝɨɜ ɬɚɤɠɟ ɜɥɢɹɟɬ ɧɚ ɪɨɫɬ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɨɩɭɯɨɥɟɣ ɧɟɨɞɧɨɡɧɚɱɧɨ [4, 8, 11, 28, 29]. ɇɟɤɨɬɨɪɵɟ ɪɟɝɭɥɹɬɨɪɵ ɮɭɧɤɰɢɨɧɚɥɶɧɨɣ ɚɤɬɢɜɧɨɫɬɢ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɮɚɝɨɰɢɬɨɜ ɨɤɚɡɵɜɚɸɬ ɩɪɨɬɢɜɨɩɨɥɨɠɧɵɣ ɷɮɮɟɤɬ ɧɚ ɪɨɫɬ ɩɟɪɜɢɱɧɨɣ ɨɩɭɯɨɥɢ ɢ ɮɨɪɦɢɪɨɜɚɧɢɟ ɦɟɬɚɫɬɚɡɨɜ [4, 11]. ɋɨɝɥɚɫɧɨ ɞɚɧɧɵɦ ɦɧɨɝɨɱɢɫɥɟɧɧɵɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɫɨɟɞɢɧɟɧɢɹ, ɜɵɡɵɜɚɸɳɢɟ ɫɬɢɦɭɥɹɰɢɸ ɋɆɎ, ɜ ɪɟɞɤɢɯ ɫɥɭɱɚɹɯ ɩɪɨɹɜɥɹɸɬ ɩɪɹɦɨɟ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɟ ɢ ɚɧɬɢɦɟɬɚɫɬɚɬɢɱɟɫɤɨɟ ɞɟɣɫɬɜɢɟ, ɤɚɤ ɩɪɚɜɢɥɨ, ɨɧɢ ɭɫɢɥɢɜɚɸɬ ɞɟɣɫɬɜɢɟ ɞɪɭɝɢɯ ɛɢɨɬɟɪɚɩɟɜɬɢɱɟɫɤɢɯ ɢ ɰɢɬɨɫɬɚɬɢɱɟɫɤɢɯ ɩɪɟɩɚɪɚɬɨɜ [2, 4, 6, 30]. Ɉɩɵɬ ɩɪɢɦɟɧɟɧɢɹ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɯ ɢɦɦɭɧɨɫɬɢɦɭɥɹɬɨɪɨɜ ɜ ɤɥɢɧɢɤɟ ɩɨɤɚɡɚɥ, ɱɬɨ ɧɟɤɨɬɨɪɵɟ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɟ ɢɦɦɭɧɨɫɬɢɦɭɥɹɬɨɪɵ ɷɮɮɟɤɬɢɜɧɵ ɬɨɥɶɤɨ ɩɪɢ ɨɩɪɟɞɟɥɟɧɧɵɯ ɜɢɞɚɯ ɪɚɤɚ, ɞɪɭɝɢɟ ɧɟ ɨɛɥɚɞɚɸɬ ɬɟɪɚɩɟɜɬɢɱɟɫɤɢɦ ɷɮɮɟɤɬɨɦ [2, 4, 6, 30]. ȼ ɧɚɲɢɯ ɪɚɧɟɟ ɩɪɨɜɟɞɟɧɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɯɢɦɢɱɟɫɤɢ ɦɨɞɢɮɢɰɢɪɨɜɚɧɧɵɟ ɤɚɪɛɨɤɫɢɦɟɬɢɥɢɪɨɜɚɧɧɵɣ (KMG) ɢ ɫɭɥɶɮɚɬɢɪɨɜɚɧɧɵɣ (SEG) ȕ-(1ĺ3)-ɝɥɢɤɚɧɵ, ɨɛɥɚɞɚɸɳɢɟ ɫɩɨɫɨɛɧɨɫɬɶɸ ɤ ɧɟɫɩɟɰɢɮɢɱɟɫɤɨɣ ɫɬɢɦɭɥɹɰɢɢ ɦɚɤɪɨɮɚɝɨɜ, ɩɨɬɟɧɰɢɪɨɜɚɥɢ ɞɟɣɫɬ123 ɀɚɧɚɟɜɚ ɋ.ə. Ɋɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɨɩɭɯɨɥɟɣ / ɫ. 121-126 ɜɢɟ ɰɢɬɨɫɬɚɬɢɱɟɫɤɨɝɨ ɩɪɟɩɚɪɚɬɚ ɰɢɤɥɨɮɨɫɮɚɧɚ (ɐɎ) ɩɪɢ ɥɟɱɟɧɢɢ ɪɚɡɥɢɱɧɵɯ ɜɢɞɨɜ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɟɪɟɜɢɜɚɟɦɵɯ ɨɩɭɯɨɥɟɣ ɭ ɦɵɲɟɣ. KMG ɢ SEG ɛɵɥɢ ɩɨɥɭɱɟɧɵ ɩɭɬɟɦ ɫɨɨɬɜɟɬɫɬɜɟɧɧɨ ɤɚɪɛɨɤɫɢɥɢɪɨɜɚɧɢɹ ɢɥɢ ɫɭɥɶɮɚɬɢɪɨɜɚɧɢɹ ɝɥɢɤɚɧɨɜ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɤɥɟɬɨɱɧɵɯ ɫɬɟɧɨɤ ɩɟɤɚɪɫɤɢɯ ɞɪɨɠɠɟɣ Saccharomyces cerevisiae [26]. KMG ɭɫɢɥɢɜɚɥ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɟ ɢ ɚɧɬɢɦɟɬɚɫɬɚɬɢɱɟɫɤɨɟ ɞɟɣɫɬɜɢɟ ɐɎ ɩɪɢ ɫɨɜɦɟɫɬɧɨɦ ɩɪɢɦɟɧɟɧɢɢ ɭ ɦɵɲɟɣ ɫ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɣ ɚɞɟɧɨɤɚɪɰɢɧɨɦɨɣ ɥɟɝɤɢɯ Ʌɶɸɢɫ (ȺɅɅ) [23, 26, 27]. SEG ɩɨɬɟɧɰɢɪɨɜɚɥ ɷɮɮɟɤɬ ɐɎ ɩɪɢ ɫɨɜɦɟɫɬɧɨɦ ɩɪɢɦɟɧɟɧɢɢ ɭ ɦɵɲɟɣ ɫ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɦ ɥɟɣɤɨɡɨɦ L 12/10 [25], ɚ ɬɚɤɠɟ ɭ ɦɵɲɟɣ ɫ ɱɭɜɫɬɜɢɬɟɥɶɧɨɣ (LS) ɢ ɪɟɡɢɫɬɟɧɬɧɨɣ (RLS) ɤ ɐɎ ɥɢɦɮɨɫɚɪɤɨɦɨɣ [24]. SEG ɨɤɚɡɵɜɚɥ ɭɦɟɪɟɧɧɨɟ ɫɚɦɨɫɬɨɹɬɟɥɶɧɨɟ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɟ ɞɟɣɫɬɜɢɟ ɜ ɨɬɧɨɲɟɧɢɢ ɥɟɣɤɨɡɚ ɦɵɲɟɣ L 12/10 [25]. ɏɢɬɨɤɚɪɛɨɤɫɢɦɟɬɢɥɢɪɨɜɚɧɧɵɣ (chitoKMG) ȕ(1ĺ3)-ɝɥɢɤɚɧ ɧɟɫɦɨɬɪɹ ɧɚ ɬɨ, ɱɬɨ ɨɧ ɨɛɥɚɞɚɥ ɫɯɨɞɧɨɣ ɫ KMG ɦɚɤɪɨɮɚɝ-ɫɬɢɦɭɥɢɪɭɸɳɟɣ ɚɤɬɢɜɧɨɫɬɶɸ [27] ɜ ɨɬɥɢɱɢɟ ɨɬ KMG ɢ SEG ɩɪɢ ɫɨɜɦɟɫɬɧɨɦ ɩɪɢɦɟɧɟɧɢɢ ɫ ɐɎ ɢɥɢ ɩɥɚɬɢɧɧɨɦ ɭ ɦɵɲɟɣ ɫ ȺɅɅ ɧɟ ɨɤɚɡɵɜɚɥ ɧɢ ɫɚɦɨɫɬɨɹɬɟɥɶɧɨɣ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɣ, ɧɢ ɩɨɬɟɧɰɢɪɭɸɳɟɣ ɞɟɣɫɬɜɢɟ ɰɢɬɨɫɬɚɬɢɤɨɜ ɚɤɬɢɜɧɨɫɬɢ. Ȼɨɥɟɟ ɬɨɝɨ, ɩɪɢ ɩɪɟɞɜɚɪɢɬɟɥɶɧɨɦ ɢɥɢ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɦ ɜɜɟɞɟɧɢɢ (ɡɚ ɱɟɬɜɟɪɨ ɫɭɬɨɤ ɢɥɢ ɱɟɪɟɡ ɱɟɬɜɟɪɨ ɫɭɬɨɤ ɩɨɫɥɟ ɜɜɟɞɟɧɢɹ ɐɎ) chitoKMG ɫɬɢɦɭɥɢɪɨɜɚɥ ɪɨɫɬ ɨɩɭɯɨɥɢ ɢ ɭɦɟɧɶɲɚɥ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɵɣ ɷɮɮɟɤɬ ɐɎ. ȼɫɟ ɬɪɢ ɝɥɸɤɚɧɚ ɧɚ ɦɨɞɟɥɢ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɣ ɩɟɪɟɜɢɜɚɟɦɨɣ ȺɅɅ ɩɪɨɹɜɥɹɥɢ ɭɦɟɪɟɧɧɭɸ ɫɚɦɨɫɬɨɹɬɟɥɶɧɭɸ ɚɧɬɢɦɟɬɚɫɬɚɬɢɱɟɫɤɭɸ ɚɤɬɢɜɧɨɫɬɶ ɢ ɩɨɬɟɧɰɢɪɨɜɚɥɢ ɚɧɬɢɦɟɬɚɫɬɚɬɢɱɟɫɤɢɣ ɷɮɮɟɤɬ ɐɎ, chitoKMG, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɤɚɡɵɜɚɥ ɩɪɨɬɢɜɨɩɨɥɨɠɧɵɣ ɷɮɮɟɤɬ ɧɚ ɪɨɫɬ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɨɩɭɯɨɥɢ ȺɅɅ [27]. Ɋɚɡɧɨɧɚɩɪɚɜɥɟɧɧɨɟ ɜɥɢɹɧɢɟ ɝɥɢɤɚɧɨɜ ɫ ɛɥɢɡɤɨɪɨɞɫɬɜɟɧɧɨɣ ɫɬɪɭɤɬɭɪɨɣ, ɯɢɦɢɱɟɫɤɢɦɢ ɢ ɛɢɨɥɨɝɢɱɟɫɤɢɦɢ ɫɜɨɣɫɬɜɚɦɢ ɦɨɠɟɬ ɡɚɜɢɫɟɬɶ ɨɬ ɬɚɤɢɯ ɮɚɤɬɨɪɨɜ ɤɚɤ ɬɪɟɬɢɱɧɚɹ ɫɬɪɭɤɬɭɪɚ ɩɨɥɢɫɚɯɚɪɢɞɨɜ, ɪɚɫɬɜɨɪɢɦɨɫɬɶ ɜ ɜɨɞɟ, ɚ ɬɚɤɠɟ ɨɬ ɫɩɨɫɨɛɚ ɢ ɦɟɫɬɚ ɜɜɟɞɟɧɢɹ. Ɉɛɥɚɞɚɹ ɫɜɨɣɫɬɜɚɦɢ ɚɬɬɪɚɤɬɚɧɬɨɜ ɦɚɤɪɨɮɚɝɨɜ, ɩɨɥɢɝɥɢɤɚɧɵ ɩɪɢ ɜɧɭɬɪɢɛɪɸɲɢɧɧɨɦ ɢɥɢ ɜɧɭɬɪɢɦɵɲɟɱɧɨɦ ɜɜɟɞɟɧɢɢ ɜ ɦɵɲɰɵ ɤɨɥɥɚɬɟɪɚɥɶɧɨɝɨ ɛɟɞɪɚ (ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɪɚɫɩɨɥɨɠɟɧɢɟɦ ɨɩɭɯɨɥɢ) ɨɬɜɥɟɤɚɸɬ ɦɚɤɪɨɮɚɝɢ ɢɡ ɨɩɭɯɨɥɢ, ɢ ɨɩɭɯɨɥɶ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɥɭɱɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɪɚɫɬɢ ɜ ɛɨɥɟɟ ɩɪɢɜɢɥɟɝɢɪɨɜɚɧɧɵɯ ɭɫɥɨɜɢɹɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɶɧɵɦɢ ɠɢɜɨɬɧɵɦɢ. ɇɚ ɦɨɞɟɥɢ ɢɫɤɭɫɫɬɜɟɧɧɨɝɨ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɨɩɭɯɨɥɟɣ ɇȺ-1 ɝɟɩɚɬɨɦɵ ɢ ɚɞɟɧɨɤɚɪɰɢɧɨɦɵ ɥɟɝɤɢɯ (ȺɅ) ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɫɬɢɦɭɥɹɰɢɹ 124 ɬɤɚɧɟɜɵɯ ɦɚɤɪɨɮɚɝɨɜ ɤɚɪɛɨɤɫɢɦɟɬɢɥɢɪɨɜɚɧɧɵɦ ȕ-(1ĺ3)-D-ɝɥɢɤɚɧɨɦ ɡɚ ɫɭɬɤɢ ɞɨ ɜɧɭɬɪɢɜɟɧɧɨɝɨ ɜɜɟɞɟɧɢɹ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɥɚ ɤ ɭɜɟɥɢɱɟɧɢɸ ɦɚɫɫɵ ɢɦɩɥɚɧɬɚɬɨɜ (ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɦɟɬɚɫɬɚɡɨɜ) ɨɩɭɯɨɥɢ ɇȺ-1 ɜ ɩɟɱɟɧɢ ɢ ɭɫɢɥɢɜɚɥɚ ɱɚɫɬɨɬɭ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɨɩɭɯɨɥɢ ȺɅ ɜ ɥɟɝɤɢɟ ɦɵɲɟɣ [29]. Ⱦɟɩɪɟɫɫɢɹ ɦɚɤɪɨɮɚɝɨɜ ɫɨɥɶɸ ɪɟɞɤɨɡɟɦɟɥɶɧɨɝɨ ɦɟɬɚɥɥɚ ɝɚɞɨɥɢɧɢɹ — GdCl3 ɡɚ ɫɭɬɤɢ ɞɨ ɜ/ɜ ɩɟɪɟɜɢɜɤɢ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ, ɢɥɢ ɢɯ ɨɬɜɥɟɱɟɧɢɟ ɚɬɬɪɚɤɬɚɧɬɚɦɢ (ɠɟɥɚɬɢɧ ɢɥɢ ɤɪɚɯɦɚɥ) ɜ ɛɪɸɲɧɭɸ ɩɨɥɨɫɬɶ, ɧɚɩɪɨɬɢɜ, ɫɩɨɫɨɛɫɬɜɨɜɚɥɢ ɩɨɞɚɜɥɟɧɢɸ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɨɩɭɯɨɥɢ ɇȺ-1 ɜ ɩɟɱɟɧɶ ɢ ɨɩɭɯɨɥɢ ȺɅ ɜ ɥɟɝɤɢɟ, ɜ ɩɨɫɥɟɞɧɟɦ ɫɥɭɱɚɟ ɭɜɟɥɢɱɢɜɚɥɚɫɶ ɩɪɨɞɨɥɠɢɬɟɥɶɧɨɫɬɶ ɠɢɡɧɢ ɠɢɜɨɬɧɵɯ [29]. Ɇɨɪɮɨɦɟɬɪɢɱɟɫɤɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɫɪɟɡɨɜ ɩɟɱɟɧɢ ɦɵɲɟɣ ɩɨɤɚɡɚɥɢ, ɱɬɨ ɩɪɟɞɜɚɪɢɬɟɥɶɧɚɹ ɞɟɩɪɟɫɫɢɹ ɦɚɤɪɨɮɚɝɨɜ ɩɟɱɟɧɢ GdCl3 ɭɦɟɧɶɲɚɥɚ ɨɛɴɟɦɧɭɸ ɩɥɨɬɧɨɫɬɶ ɞɟɫɬɪɭɤɬɢɜɧɵɯ ɩɨɪɚɠɟɧɢɣ ɭ ɦɵɲɟɣ-ɨɩɭɯɨɥɟɧɨɫɢɬɟɥɟɣ, ɚ ɬɚɤɠɟ ɫɧɢɠɚɥɚ ɨɛɴɟɦɧɭɸ ɩɥɨɬɧɨɫɬɶ ɢɦɩɥɚɧɬɚɬɨɜ ɨɩɭɯɨɥɢ ɜ ɩɟɱɟɧɢ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɶɧɵɦɢ ɠɢɜɨɬɧɵɦɢ [28]. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɧɚɦɢ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɧɚ ɨɩɪɟɞɟɥɟɧɧɵɯ ɷɬɚɩɚɯ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɹ ɚɤɬɢɜɚɰɢɹ ɤɥɟɬɨɤ ɫɢɫɬɟɦɵ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɮɚɝɨɰɢɬɨɜ ɦɨɠɟɬ ɨɤɚɡɚɬɶɫɹ ɜɪɟɞɧɨɣ, ɫɬɢɦɭɥɹɰɢɹ ɬɤɚɧɟɜɵɯ ɦɚɤɪɨɮɚɝɨɜ ɦɨɠɟɬ ɩɪɢɜɨɞɢɬɶ ɤ ɭɜɟɥɢɱɟɧɢɸ ɤɨɥɢɱɟɫɬɜɚ ɢɦɩɥɚɧɬɢɪɭɸɳɢɯɫɹ ɜ ɨɪɝɚɧɟ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ, ɬɨɝɞɚ ɤɚɤ ɩɨɞɚɜɥɟɧɢɟ ɢɯ ɮɭɧɤɰɢɢ — ɤ ɟɝɨ ɭɦɟɧɶɲɟɧɢɸ. ȼ ɫɥɭɱɚɟ ɩɪɢɦɟɧɟɧɢɹ GdCl3 ɝɚɞɨɥɢɧɢɣ, ɧɚɤɚɩɥɢɜɚɹɫɶ ɜ ɥɢɡɨɫɨɦɚɯ, ɩɨɞɚɜɥɹɟɬ ɫɩɨɫɨɛɧɨɫɬɶ ɦɚɤɪɨɮɚɝɨɜ ɤ ɪɟɰɟɩɬɨɪɧɨ-ɨɩɨɫɪɟɞɨɜɚɧɧɨɦɭ ɮɚɝɨɰɢɬɨɡɭ [28, 29], ɱɬɨ, ɩɨ-ɜɢɞɢɦɨɦɭ, ɢ ɩɪɢɜɨɞɢɬ ɤ ɫɧɢɠɟɧɢɸ ɡɚɯɜɚɬɚ ɢɦɢ ɰɢɪɤɭɥɢɪɭɸɳɢɯ ɜ ɤɪɨɜɢ ɨɩɭɯɨɥɟɜɵɯ ɤɥɟɬɨɤ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɪɢɜɟɞɟɧɧɵɟ ɜɵɲɟ ɮɚɤɬɵ ɝɨɜɨɪɹɬ ɨ ɬɨɦ, ɱɬɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɨɩɭɯɨɥɢ ɢ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɵ ɧɟ ɜɫɟɝɞɚ ɧɨɫɢɬ ɚɧɬɚɝɨɧɢɫɬɢɱɟɫɤɢɣ ɯɚɪɚɤɬɟɪ. Ɋɚɧɟɟ ɫɮɨɪɦɢɪɨɜɚɧɧɵɟ ɩɨɫɬɭɥɚɬɵ ɩɪɨɬɢɜɨɨɩɭɯɨɥɟɜɨɝɨ ɢɦɦɭɧɢɬɟɬɚ, ɫɨɝɥɚɫɧɨ ɤɨɬɨɪɵɦ ɢɦɦɭɧɧɵɟ ɪɟɚɤɰɢɢ ɨɪɝɚɧɢɡɦɚ ɧɚɩɪɚɜɥɟɧɵ ɧɚ ɭɧɢɱɬɨɠɟɧɢɟ ɨɩɭɯɨɥɢ, ɚ ɪɚɡɜɢɬɢɟ ɢ ɩɪɨɝɪɟɫɫɢɪɨɜɚɧɢɟ ɨɩɭɯɨɥɟɣ ɹɜɥɹɟɬɫɹ ɫɥɟɞɫɬɜɢɟɦ ɢɦɦɭɧɨɞɟɮɢɰɢɬɚ, ɜ ɧɚɫɬɨɹɳɟɟ ɜɪɟɦɹ ɩɪɟɞɫɬɚɜɥɹɸɬɫɹ ɭɩɪɨɳɟɧɧɵɦɢ. ɂɦɦɭɧɧɚɹ ɫɢɫɬɟɦɚ ɦɨɠɟɬ ɧɟ ɬɨɥɶɤɨ ɨɬɬɨɪɝɚɬɶ ɨɩɭɯɨɥɶ, ɧɨ ɢ ɚɤɬɢɜɧɨ ɩɨɦɨɝɚɬɶ ɨɩɭɯɨɥɟɜɨɣ ɩɪɨɝɪɟɫɫɢɢ [8, 11]. ȼɵɫɤɚɡɵɜɚɟɬɫɹ ɦɧɟɧɢɟ, ɱɬɨ ɩɪɢɦɟɧɟɧɢɟ ɧɟɫɩɟɰɢɮɢɱɟɫɤɢɯ ɢɦɦɭɧɨɬɟɪɚɩɟɜɬɢɱɟɫɤɢɯ ɫɪɟɞɫɬɜ ɦɨɠɟɬ ɛɵɬɶ ɷɮɮɟɤɬɢɜɧɨ ɥɢɲɶ ɩɪɢ ɨɩɪɟɞɟɥɟɧɧɵɯ ɭɫɥɨɜɢɹɯ — ɧɚ ɪɚɧɧɢɯ ɷɬɚɩɚɯ ɪɚɡɜɢɬɢɹ ɨɩɭɯɨɥɢ ɢ ɟɫɥɢ ɢɦɦɭɧɧɚɹ ɫɢɫɬɟɦɚ ɜ ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „. ɀɚɧɚɟɜɚ ɋ.ə. Ɋɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɨɩɭɯɨɥɟɣ / ɫ. 121-126 ɦɨɦɟɧɬ ɢɦɦɭɧɢɡɚɰɢɢ ɫɨɯɪɚɧɹɟɬ ɫɜɨɸ ɤɨɦɩɟɬɟɧɬɧɨɫɬɶ [8, 11]. ɉɨ ɞɚɧɧɵɦ Prehn (2004) ɩɪɢɦɟɧɟɧɢɟ ɢɦɦɭɧɨɫɬɢɦɭɥɢɪɭɸɳɢɯ ɫɪɟɞɫɬɜ ɜ ɭɫɥɨɜɢɹɯ ɞɢɫɮɭɧɤɰɢɢ ɢɦɦɭɧɢɬɟɬɚ ɩɪɢ ɝɟɧɟɪɚɥɢɡɚɰɢɢ ɨɧɤɨɥɨɝɢɱɟɫɤɨɝɨ ɡɚɛɨɥɟɜɚɧɢɹ ɦɨɠɟɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɩɪɨɝɪɟɫɫɢɢ ɢ ɭɫɢɥɢɜɚɬɶ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɨɩɭɯɨɥɟɣ [11]. ȼ ɫɜɹɡɢ ɫ ɷɬɢɦ ɪɚɡɪɚɛɚɬɵɜɚɸɬɫɹ ɧɨɜɵɟ ɩɨɞɯɨɞɵ, ɧɚɩɪɚɜɥɟɧɧɵɟ ɧɚ ɩɨɜɵɲɟɧɢɟ ɬɭɦɨɪɢɰɢɞɧɵɯ ɫɜɨɣɫɬɜ ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɯ ɫ ɨɩɭɯɨɥɶɸ ɦɚɤɪɨɮɚɝɨɜ, ɩɨɢɫɤ ɢ ɩɪɢɦɟɧɟɧɢɟ ɢɦɦɭɧɨɦɨɞɭɥɹɬɨɪɨɜ, ɜɵɡɵɜɚɸɳɢɯ ɞɥɢɬɟɥɶɧɭɸ ɫɬɚɛɢɥɢɡɚɰɢɸ ɦɚɤɪɨɮɚɝɨɜ ɜ ɰɢɬɨɬɨɤɫɢɱɟɫɤɨɣ ɮɚɡɟ [4, 8, 11, 18, 22]. THE ROLE OF STIMULATION AND DEPRESSION OF MACROPHAGES IN TUMOR GROWTH AND METASTASES S.Ya. Zhanaeva, T.V. Alekseenko, T.A. Korolenko The modern data about the relationship of tumors and macrophages are presented in the current review. The own and literature data on interaction (of antagonistic and “collaborative” character) between tumor and immune system are presented. In some conditions macrophage was shown to promote tumor progression. The dual interaction of nonspecific cellular part of immune system and tumor and the role of stimulation and depression of macrophages in tumor growth and metastases is discussed. Ʌɢɬɟɪɚɬɭɪɚ 1. Ƚɟɨɪɝɢɟɜ Ƚ.ɉ. Ɇɨɥɟɤɭɥɹɪɧɨ–ɝɟɧɟɬɢɱɟɫɤɢɟ ɦɟɯɚɧɢɡɦ ɩɪɨɝɪɟɫɫɢɢ ɨɩɭɯɨɥɟɣ / Ƚ.ɉ. Ƚɟɨɪɝɢɟɜ // ɋɨɪɨɫ. ɨɛɪ. ɠɭɪɧɚɥ. – 2000. – Ɍ.6. – ʋ11. – ɋ.2-7. 2. Ȼɚɪɵɲɧɢɤɨɜ Ⱥ.ɘ. ɉɪɢɧɰɢɩɵ ɢ ɩɪɚɤɬɢɤɚ ɜɚɤɰɢɧɨɬɟɪɚɩɢɢ ɪɚɤɚ / Ⱥ.ɘ. Ȼɚɪɵɲɧɢɤɨɜ // Ȼɸɥ. ɋɈ ɊȺɆɇ. – 2004. – ʋ 2. – ɋ. 61-67. 3. Ʉɨɡɥɨɜ ȼ.Ⱥ. ɋɨɜɪɟɦɟɧɧɵɟ ɩɪɨɛɥɟɦɵ ɢɦɦɭɧɨɬɟɪɚɩɢɢ ɜ ɨɧɤɨɥɨɝɢɢ / ȼ.Ⱥ. Ʉɨɡɥɨɜ, ȿ.Ɋ. ɑɟɪɧɵɯ // Ȼɸɥ. ɋɈ ɊȺɆɇ – 2004. – ʋ 2. – ɋ. 12-19. 4. Ɇɨɪɬɨɧ Ⱦ.Ʌ. Ȼɢɨɥɨɝɢɱɟɫɤɢɟ ɦɟɬɨɞɵ ɥɟɱɟɧɢɹ ɨɧɤɨɥɨɝɢɱɟɫɤɢɯ ɡɚɛɨɥɟɜɚɧɢɣ. / Ⱦ.Ʌ. Ɇɨɪɬɨɧ, Ⱥ. Ȼɚɪɬ. – Ɇ., 2002. – ɋ. 710-724. 5. ɉɨɩɨɜɚ ɇ.Ⱥ. ɂɦɦɭɧɢɬɟɬ ɩɪɨɬɢɜ ɨɩɭɯɨɥɟɣ. Ɇɢɮ ɢɥɢ ɪɟɚɥɶɧɨɫɬɶ? / ɇ.Ⱥ. ɉɨɩɨɜɚ // ɋɨɪɨɫ. ɨɛɪ. ɠɭɪɧɚɥ. – 2001. – Ɍ. 7. – ʋ 3. – ɋ.12-17. 6. Borchers A.T. Mushrooms, tumors and immunity: an update / A.T. Borchers, C.L. Keen, M.E. Gershwin // Exp. Biol. Med. – 2004. – Vol. 229. – P. 393-406. 7. Mechanism by with orally administered ȕ-1,3glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumours models / F. Hong, J.T. Baran, D.J. Allendorf, et al. // J. Immunol. – 2004. – Vol. 173. – P. 797-806. 8. Lewis C. Macrophage responses to hypoxia / C. Lewis, C. Murdoch // Am. J. Ɋathol. – 2005. – Vol. 167. – ʋ 3. – P. 627-634. 9. Murdoch C. Mechanisms regulating the recruitment ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „. of macrophages into hypoxic areas of tumors and other ischemic tissues / C. Murdoch, A. Giannoudis, C.E. Lewis // Blood. – 2004. – Vol. 104. – P. 2224-2234. 10. Identification of tumor-infiltrating macrophages as the killers of tumor cells after immunization in a rat model system / B. Bonnotte, N. Larmonier, N. Favre, et al. // J. Immunol. – 2001. – Vol. 167. – P. 5077-5083. 11. Prehn T. An immune reaction may be necessary for cancer development / T. Prehn // Theor. Biol. and Med. Modeling. – 2006. – Vol. 3. – ʋ 6. – P. 10-21. 12. Eerola A-K. A high number of tumor–infiltrating lymphocytes are associated with a small tumor size, low tumor stage, and a favorable prognosis in operated small cell lung carcinoma1 / A-K. Eerola, Y. Soini, P. Paakko // Clin. Cancer Res. – 2000. – Vol. 6. – P. 1875-1881. 13. Tumoricidal response of liver macrophages isolated from rats bearing liver metastases of colon adenocarcinoma. / C. Thomas, A.M. Nijenhuis, B. Dontje, et al. // J. Leukocyte Biol. –1995. – Vol. 57. – ʋ 4. – P. 617-623. 14. Leek R.D. Tumor associated macrophages in breast cancer / R.D. Leek, A.L. Harris // J. Mamm. Gland. Biol. Neoplasia. – 2002. – Vol. 7. – P. 177-189. 15. Vascular endothelial growth factor secretion by tumor–infiltrating macrophages essentially supports tumor angiogenesis IgG immune complexes potentiate the process / E. Barbera-Guillem, J.K. Nyhus, C.C. Wolford, et al. // Cancer Res. – 2002. – Vol. 62. – P. 7042-7049. 16. Grimshaw M.J. Endothelin-2 is a macrophage chemoattractant : implication for macrophage distribution in tumors / M.J. Grimshaw, J.L. Wilson, F.R. Balkwill // Eur. J. Immunol. – 2002. – Vol. 32. – P. 2393-2400. 17. Bingle L. The role of tumor-associated macrophages in tumor progression: implications for new anticancer therapies / L. Bingle, N.J. Brown, C.E. Lewis // J. Pathol. – 2002. – Vol. 196. – P. 254-265. 18. Macrophage polarization: tumor associated macrophages as a paradigm for polarized M2 mononuclear phagocytes / A. Mantovani, S. Sozzani, M. Lacati, et al. // Trends Immunol. – 2002. – Vol. 23. – P. 549-555. 19. Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice / S. Aharinejad, P. Paulus, M. Sioud, et al. // Cancer Res. – 2004. – Vol. 64. – P. 5378-5384. 20. Fusion hybrids with macrophage and melanoma cells up-regulate N-acetylglucosaminyltransferase V, ȕ1-6 branching and metastasis / A.K. Chakraborty, J. Pawelek, Y. Ikeda, et al. // Cell Growth and Diff. – 2001. – Vol. 12. – P. 623-630. 21. Enhansed invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha depended up-regulation of matrix metalloproteases / T. Hagemann, S.C. Robinson, M. Schulz, et al. // Carcinogenesis. – 2004. – Vol. 25. – P. 1543-1549. 22. Ɉɤɭɥɨɜ ȼ.Ȼ. Ⱥɤɬɭɚɥɶɧɵɟ ɩɪɨɛɥɟɦɵ ɢɦɦɭɧɨɬɟɪɚɩɢɢ ɨɩɭɯɨɥɟɣ ɜ ɤɨɧɬɟɤɫɬɟ ɷɜɨɥɸɰɢɨɧɧɨ ɡɚɤɪɟɩɥɟɧɧɨɣ ɪɟɚɤɰɢɢ ɦɚɤɪɨɮɚɝɚ ɧɚ ɩɨɜɪɟɠɞɟɧɢɟ ɬɤɚɧɟɣ / ȼ.Ȼ. Ɉɤɭɥɨɜ // ȼɨɩɪ. ɨɧɤɨɥ. – 1998. – Ɍ. 43. – ʋ 1. – ɋ. 102-106. 23. ɍɜɟɥɢɱɟɧɢɟ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɯɢɦɢɨɬɟɪɚɩɢɢ ɤɚɪɰɢɧɨɦɵ ɥɟɝɤɢɯ ɫɬɢɦɭɥɹɬɨɪɨɦ ɦɚɤɪɨɮɚɝɨɜ ɤɚɪɛɨɤɫɢɦɟɬɢɥɢɪɨɜɚɧɧɵɦ (1ĺ3)-ȕ-D-ɝɥɸɤɚɧɨɦ / Ɉ.ȼ. Ɏɚɥɚɦɟɟɜɚ, Ɉ.ɇ. ɉɨɬɟɪɹɟɜɚ, ɋ.ə. ɀɚɧɚɟɜɚ ɢ ɞɪ. // Ȼɸɥ. ɷɤɫɩɟɪ. ɛɢɨɥ. ɦɟɞɢɰɢɧɵ. – 2001. – ʋ 8. – ɋ. 205-208. 24. Regulation of activity of cathepsin B, L and D in murine lymphosarcoma model at combined treatment with cyclophosphamide and yeast polysaccharide / T.A. Khalikova, 125 ɀɚɧɚɟɜɚ ɋ.ə. Ɋɨɥɶ ɫɬɢɦɭɥɹɰɢɢ ɢ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɜ ɪɚɡɜɢɬɢɢ ɢ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɢ ɨɩɭɯɨɥɟɣ / ɫ. 121-126 S.Ya. Zhanaeva, T.A. Korolenko, et al. // Cancer Lett. – 2005. – Vol. 2. – P. 1-7 25. Enhancing effect of new biological response modifier sulphoethylated (1ĺ3)-ȕ-D-glucan on untitumor activity of cyclophosphamide in the treatment of experimental murine leukoses / T.A. Khalikova, S.Ya. Zhanaeva, T.A. Korolenko, et al. // Exper. Oncol. – 2007. – Vol. 28. – ʋ 4. – P. 308-313. 26. Increased efficiency of Lewis lung carcinoma chemotherapy with a macrophage stimulators — yeast carboxymethyl glucan / G. Kogan, J. Sandula, T.A. Korolenko, et al. // Intern. Immunopharmacol. – 2002. –Vol. 2. – P. 775-781. 27. Effect of different biological response modifiers on growth and metastasizing of murine Lewis lung adenocarcinoma. / S.Ya. Zhanaeva, O.V. Falameeva, T.G. Filatova, et al. // 126 Int. J. Immunotherapy. – 2003. – Vol. 19 (2-4). – P. 141-150. 28. ȼɥɢɹɧɢɟ ɞɟɩɪɟɫɫɢɢ ɦɚɤɪɨɮɚɝɨɜ ɩɟɱɟɧɢ ɧɚ ɪɚɡɜɢɬɢɟ ɜɧɭɬɪɢɩɟɱɟɧɨɱɧɵɯ ɦɟɬɚɫɬɚɡɨɜ ɨɩɭɯɨɥɢ ɇȺ-1 ɭ ɦɵɲɟɣ / ɋ.ə. ɀɚɧɚɟɜɚ, Ɍ.Ⱥ. Ʉɨɪɨɥɟɧɤɨ, ȿ.ȼ. ɇɢɤɢɬɟɧɤɨ ɢ ɞɪ. // Ȼɸɥ. ɷɤɫɩɟɪ. ɛɢɨɥ. ɦɟɞ. – 2004. – Ɍ. 137. – ʋ 6. – ɋ. 660-663. 29. ɋɬɢɦɭɥɹɰɢɹ ɦɚɤɪɨɮɚɝɨɜ ɭɫɢɥɢɜɚɟɬ, ɚ ɞɟɩɪɟɫɫɢɹ ɬɨɪɦɨɡɢɬ ɦɟɬɚɫɬɚɡɢɪɨɜɚɧɢɟ ɞɜɭɯ ɩɟɪɟɜɢɜɚɟɦɵɯ ɨɩɭɯɨɥɟɣ ɦɵɲɟɣ ɜ ɥɟɝɤɢɟ ɢ ɩɟɱɟɧɶ / ɋ.ə. ɀɚɧɚɟɜɚ, Ɍ.Ⱥ. Ʉɨɪɨɥɟɧɤɨ, Ȼ.Ƚ. ɇɟɤɪɚɫɨɜ ɢ ɞɪ. // Ȼɸɥ. ɷɤɫɩɟɪ. ɛɢɨɥ. ɦɟɞ. – 2005. – Ɍ. 140. – ʋ 4. – ɋ. 450-452. 30. McCarty M.F. Toward a core nutraceutical program for cancer management / M.F. McCarty, K.I. Block // Integr. Cancer Therapies. – 2006. – Vol. 5. – ʋ 2. – P. 150-171. ¡fiÀÀ“Õ‹ –Œ —¿ÃÕ, ʋ 3 (125), 2007 „.
