ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vitro ΠΈ in vivo
Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΡΠΆΠ΅ΡΠΎΠ΄Π½ΠΎΠΉ ΠΠΠ Π² ΡΡΠΊΠ°ΡΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ (Yang, 1992; Desnick and Schuchman, 1998). Π ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΡΡΡΡ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΎΠ±Π»Π°ΡΡΠΈ ΡΠΈΡΡΠ΅ΠΌ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΠΠΠ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ , Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ — ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ. Π Π΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ Π΄ΠΎΡΡΠ°Π²ΠΊΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠΎΡΠ΅ΡΠ°Π΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- Π‘ΠΏΠΈΡΠΎΠΊ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΠΉ
- ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- 1. Π Π΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ
- 1. 1. ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΠ΅ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Π΄Π»Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ
- 1. 1. 1. ΠΠΠ
- 1. 1. 2. ΠΠΈΠ³Π°Π½Π΄Ρ
- 1. 1. 3. ΠΠΎΠ»ΠΈΠΊΠ°ΡΠΈΠΎΠ½Ρ
- 1. 1. 4. ΠΠΎΠΌΠΏΠ°ΠΊΡΠΈΠ·Π°ΡΠΈΡ ΠΠΠ ΠΈ ΡΠ°Π·ΠΌΠ΅ΡΡ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΡΡΡΡΠΈΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ²
- 1. 2. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ
ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ
- 1. 2. 1. ΠΠ½Π΄ΠΎΡΠΈΡΠΎΠ·
- 1. 2. 2. ΠΠ½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΡΡΠ°Π½ΡΠΏΠΎΡΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ
- 1. 2. 2. 1. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ ΡΠ΅ΡΠ΅Π· ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ ΡΠ½Π΄ΠΎΡΠΎΠΌ
- 1. 2. 2. 2. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ Π² ΡΠ΄ΡΠΎ
- 1. 1. ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΠ΅ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Π΄Π»Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ
- 2. 1. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ²
- 2. 2. ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² Π½Π° ΡΡΠ°Π½ΡΠΏΠΎΡΡ ΠΌΠ°ΠΊΡΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ» Π² ΠΊΠ»Π΅ΡΠΊΠΈ
- 2. 3. Π£ΡΠΈΠ»Π΅Π½ΠΈΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π°
- 2. 4. ΠΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² Π² ΡΠΈΡΡΠ΅ΠΌΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΠΠΠ
- 2. 5. ΠΠ΅ΠΉΡΡΠ²ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² Π½Π° Π΄ΡΡΠ³ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ
- 3. 1. Π‘ΠΏΠΎΡΠΎΠ±Ρ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ in vivo
- 3. 2. ΠΠ΅ΠΊΠΎΡΠΎΡΡΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ Ρ vivo
- 3. 2. 1. ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅
- 3. 2. 2. ΠΡΡΠΈ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΡΠ°Π½ΡΠ³Π΅Π½Π°
- 3. 2. 2. 1. Π§Π°ΡΡΠΈΡΠ½Π°Ρ Π³Π΅ΠΏΠ°ΡΡΠΊΡΠΎΠΌΠΈΡ
- 3. 2. 2. 2. ΠΠΏΡΠΈΠΌΠ°Π»ΡΠ½Π°Ρ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΡ ΠΠΠ
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vitro ΠΈ in vivo (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
14. ΠΠ½Π°Π»ΠΈΠ· Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Ρ.44.
14.1. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ ΠΈ ΡΠΊΠ°Π½Π΅Π²ΡΡ Π»ΠΈΠ·Π°ΡΠΎΠ².44.
14.2 ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ Π±Π΅Π»ΠΊΠ° Π² ΠΏΡΠΎΠ±Π°Ρ .45.
14.3. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Ρ.45.
15. ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡ Π°Π½Π°Π»ΠΈΠ·.45.
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ.46.
1. Π‘Π±ΠΎΡΠΊΠ° ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ.46.
1.1. Π‘ΠΈΠ½ΡΠ΅Π· ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ.46.
1.2. ΠΡΠ΅Π½ΠΊΠ° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΠΠ Ρ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠΎΠΌ ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½.46.
1.3. Π‘Π±ΠΎΡΠΊΠ° ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ.48.
2. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ Π² ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ ΠΠ‘-11 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π²ΠΈΠ΄Π΅ΠΎΠΈΠ½ΡΠ΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΠΈ.49.
2.1. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠ° ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½.49.
2.2. Π’ΡΠ°Π½ΡΠΏΠΎΡΡ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎ-ΠΌΠ΅ΡΠ΅Π½Π½ΠΎΠΉ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠ΅ΠΉ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Π² ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ ΠΠ‘-11.51.
2.3. ΠΠ½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ.53.
3. ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² Π½Π° ΠΏΡΠΎΠ½ΠΈΡΠ°Π΅ΠΌΠΎΡΡΡ ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠΈΠ΄Π½ΠΎΠΉ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ.54.
3.1. ΠΡΡ ΠΎΠ΄ ΡΠΎΠ΄Π΅ΡΠΆΠΈΠΌΠΎΠ³ΠΎ Π»ΠΈΠΏΠΎΡΠΎΠΌ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ².54.
3.2. ΠΠ΅ΠΌΠ±ΡΠ°Π½ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠ°, Π²ΠΊΠ»ΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ Π² ΡΠΎΡΡΠ°Π² ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠ΅ΠΉ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ.56.
4. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΌΡΡΠΈ in vitro.59.
4.1. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΌΡΡΠΈ Π»ΠΈΠ½ΠΈΠΈ ΠΠ‘-11 ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠ΅ΠΉ ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½-ΠΠΠ.59.
4.2. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² Π΄Π»Ρ ΡΡΠΈΠ»Π΅Π½ΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ.60.
4.2.1. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΡΠ²ΠΎΠ±ΠΎΠ΄Π½ΡΡ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ².60.
4.2.2. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΡΠΌΠΈ (ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½)-ΠΠΠ-(ΡΡΡΠ΅ΠΏΡΠ°Π²ΠΈΠ΄ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½)-Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡ.61.
4.2.3. ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ Π²ΠΈΡΡΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ.64.
5. Π Π΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· in vivo.66.
5.1. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· ΠΌΡΡΠΈ.66.
5.2. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· ΠΎΠ²Π΅Ρ.69.
6. Π‘Π΅ΠΊΡΠ΅ΡΠΈΡ ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Ρ Π² ΠΌΠΎΠ»ΠΎΠΊΠΎ ΠΏΠΎΡΠ»Π΅ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vivo.71.
6.1. Π‘Π΅ΠΊΡΠ΅ΡΠΎΡΠ½ΡΠ΅ ΡΠΎΡΠΌΡ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Ρ.71.
6.2. ΠΠ½Π°Π»ΠΈΠ· Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Ρ Π² ΠΌΠΎΠ»ΠΎΠΊΠ΅ ΡΡΠ°Π½ΡΠ³Π΅Π½Π½ΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ .72.
ΠΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ².75.
ΠΡΠ²ΠΎΠ΄Ρ.83.
Π‘ΠΏΠΈΡΠΎΠΊ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
84.
ΠΠ»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΠΈ.100.
Π‘ΠΏΠΈΡΠΎΠΊ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΠΉ.
Ad2 — Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΡΠ΅ΡΠΎΡΠΈΠΏ 2 Ad5 — Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΡΠ΅ΡΠΎΡΠΈΠΏ 5.
BES — Π, Π-Π±ΠΈΡ (2-ΠΎΠΊΡΠΈΡΡΠΈΠ»)-2-Π°ΠΌΠΈΠ½ΠΎΡΡΠ°Π½ΡΡΠ»ΡΡΠΎΠ½ΠΎΠ²Π°Ρ ΠΊΠΈΡΠ»ΠΎΡΠ° CELO — Chicken Embryo Lethal Orphan CMV — ΡΠΈΡΠΎΠΌΠ΅Π³Π°Π»ΠΎΠ²ΠΈΡΡΡ.
EDS-76 — Egg Drop Syndrome-76 Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΉΡΠ΅Π½ΠΎΡΠΊΠΎΡΡΠΈ EGF — ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΡΠΉ ΡΠ°ΠΊΡΠΎΡ ΡΠΎΡΡΠ° HBS — 25 ΠΌΠ HEPES, ΡΠ 7,5, 150 ΠΌΠ NaCl.
HEPES — Π-(2-ΠΎΠΊΡΠΈΡΡΠΈΠ»)ΠΏΠΈΠΏΠ΅ΡΠ°Π·ΠΈΠ½-ΠΡΠ'-(2-ΡΡΠ°Π½ΡΡΠ»ΡΡΠΎΠ½ΠΎΠ²Π°Ρ ΠΊΠΈΡΠ»ΠΎΡΠ°) LA — Π°-Π»Π°ΠΊΡΠ°Π»ΡΠ±ΡΠΌΠΈΠ½ Luc — Π»ΡΡΠΈΡΠ΅ΡΠ°Π·Π°.
NHS-AC-Π±ΠΈΠΎΡΠΈΠ½ — N-ΠΎΠΊΡΠΈΡΡΠΊΡΠΈΠ½ΠΈΠΌΠΈΠ΄Π½ΡΠΉ ΡΡΠΈΡ Π±ΠΈΠΎΡΠΈΠ½Π°ΠΌΠΈΠ΄ΠΎΠΊΠ°ΠΏΡΠΎΠ°ΡΠ° RSY — Π²ΠΈΡΡΡ ΡΠ°ΡΠΊΠΎΠΌΡ Π Π°ΡΡΠ° SDS — Π΄ΠΎΠ΄Π΅ΡΠΈΠ»ΡΡΠ»ΡΡΠ°Ρ Π½Π°ΡΡΠΈΡ.
SpBLG — ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΉ ΠΏΠ΅ΠΏΡΠΈΠ΄ ΠΎΠ²Π΅ΡΡΠ΅Π³ΠΎ Π -Π»Π°ΠΊΡΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½Π°.
SPDP — N-ΡΡΠΊΡΠΈΠ½ΠΈΠΌΠΈΠ΄ΠΈΠ» 3-(2-ΠΏΠΈΡΠΈΠ΄ΠΈΠ»Π΄ΠΈΡΠΈΠΎ)ΠΏΡΠΎΠΏΠΈΠΎΠ½Π°Ρ.
ΠΠ‘Π — Π±ΡΡΠΈΠΉ ΡΡΠ²ΠΎΡΠΎΡΠΎΡΠ½ΡΠΉ Π°Π»ΡΠ±ΡΠΌΠΈΠ½ Π².Ρ. — Π²ΠΈΡΡΡΠ½ΡΠ΅ ΡΠ°ΡΡΠΈΡΡ.
ΠΠ’Π’ — Π΄ΠΈΡΠΈΠΎΡΡΠ΅ΠΈΡΠΎΠ» ΠΎ.Π΅. — ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΡΠ²Π΅ΡΠΎΠ²ΡΠ΅ Π΅Π΄ΠΈΠ½ΠΈΡΡ Ρ.ΠΏ.Π½. — ΡΡΡΡΡΠ° ΠΏΠ°Ρ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ΠΎΠ².
Π€ΠΠ’Π¦ — ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅ΠΈΠ½ΠΈΠ·ΠΎΡΠΈΠΎΡΠΈΠ°Π½Π°Ρ.
ΠΠΠ’Π — ΡΡΠΈΠ»Π΅Π½Π³Π»ΠΈΠΊΠΎΠ»Ρ, Π±ΠΈΡ (2-Π°ΠΌΠΈΠ½ΠΎΡΡΠΈΠ»ΠΎΠ²ΡΠΉ ΡΡ ΠΈΡ)-Π«, N, N ', N ' -ΡΠ΅ΡΡΠ°Π°ΡΠ΅ΡΠ°Ρ ΠΠΠ’Π — ΡΡΠΈΠ»Π΅Π½Π΄ΠΈΠ°ΠΌΠΈΠ½ΡΠ΅ΡΡΠ°Π°ΡΠ΅ΡΠ°Ρ.
Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²Π°Π½Ρ ΠΈ ΠΎΡ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½Ρ ΡΠΎΡΠ½ΠΈ Π³Π΅Π½ΠΎΠ², ΠΊΠΎΠ΄ΠΈΡΡΡΡΠΈΡ Π±Π΅Π»ΠΊΠΈ, ΠΈΠΌΠ΅ΡΡΠΈΠ΅ Π±ΠΎΠ»ΡΡΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄Π»Ρ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Ρ ΠΈ Π΄ΡΡΠ³ΠΈΡ ΠΏΠΎΡΡΠ΅Π±Π½ΠΎΡΡΠ΅ΠΉ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ°ΠΊΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Π² Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΡΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π°Ρ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· Π²Π°ΠΆΠ½ΡΡ Π·Π°Π΄Π°Ρ Π±ΠΈΠΎΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΈ ΠΎΡΠΈΡΡΠΊΠ° Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈΠ· ΠΊΡΠΎΠ²ΠΈ ΠΈΠ»ΠΈ ΡΠΊΠ°Π½Π΅ΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ Π΄ΠΎΡΠΎΠ³ΠΎΡΡΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π΄ΡΡΠΎΠΉ, ΡΠΎΠΏΡΡΠΆΠ΅Π½Π½ΠΎΠΉ Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ°ΠΌΠΈΠ½Π°ΡΠΈΠ΅ΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΡΠΌΠΈ Π°Π³Π΅Π½ΡΠ°ΠΌΠΈ. Π Π°Π·Π²ΠΈΡΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π³Π΅Π½Π½ΠΎΠΉ ΠΈΠ½ΠΆΠ΅Π½Π΅ΡΠΈΠΈ ΠΏΡΠΈΠ²Π΅Π»ΠΎ ΠΊ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ ΡΠΈΡΡΠ΅ΠΌ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΡΠ΅Π±ΡΠ΅ΠΌΡΡ Π±Π΅Π»ΠΊΠΎΠ². ΠΠ΄Π½Π°ΠΊΠΎ, Π² Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ ΡΠΈΡΡΠ΅ΠΌΠ°Ρ Π½Π΅ Π²ΡΠ΅Π³Π΄Π° ΡΠ΄Π°Π΅ΡΡΡ ΠΎΡΡΡΠ΅ΡΡΠ²ΠΈΡΡ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΡΠΊΠ°ΡΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ Π±Π΅Π»ΠΊΠΎΠ², ΡΠ°ΠΊΠΈΠ΅ ΠΊΠ°ΠΊ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅, Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈ Π°ΠΌΠΈΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅. Π‘ ΡΡΠΎΠΉ ΠΆΠ΅ ΡΠ΅Π»ΡΡ ΠΌΠΎΠ³ΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡΡΡ ΡΡΠΊΠ°ΡΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΈΡΡΠ΅ΠΌΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ — ΠΌΠ°ΡΡΡΠ°Π±Π½ΠΎΠ΅ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ . ΠΠ΅Π΄ΠΎΡΡΠ°ΡΠΊΠΎΠΌ ΡΡΠΊΠ°ΡΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠΈΡΡΠ΅ΠΌ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡ Π½ΠΈΠ·ΠΊΠ°Ρ ΡΠ΅Π½ΡΠ°Π±Π΅Π»ΡΠ½ΠΎΡΡΡ, Ρ.ΠΊ. Π΄Π»Ρ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ΅Π±ΡΡΡΡΡ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π±ΠΎΠ»ΡΡΠΈΠ΅ Π·Π°ΡΡΠ°ΡΡ, Π° Π²ΡΡ ΠΎΠ΄ ΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Π½Π΅ Π²Π΅Π»ΠΈΠΊΠΈ. ΠΡΡΠ³ΠΎΠ΅ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΎ Π½Π° ΡΠΎΠ·Π΄Π°Π½ΠΈΠΈ ΡΡΠ°Π½ΡΠ³Π΅Π½Π½ΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ -Π±ΠΈΠΎΡΠ΅Π°ΠΊΡΠΎΡΠΎΠ², ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ ΠΏΡΠΎΠ΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠ΅Π»Π΅Π²ΡΠ΅ Π±Π΅Π»ΠΊΠΈ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠΈΡΠΎΠ²Π°ΡΡ ΠΈΡ Π²ΠΎ Π²Π½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ ΠΆΠΈΠ΄ΠΊΠΎΡΡΠΈ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°.
Π ΡΡΠΎΠΉ ΡΠ²ΡΠ·ΠΈ ΠΌΠΎΠ»ΠΎΡΠ½Π°Ρ ΠΆΠ΅Π»Π΅Π·Π° ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΌ Π±ΠΈΠΎΡΠ΅Π°ΠΊΡΠΎΡΠΎΠΌ Π΄Π»Ρ ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΡΠ΅ΠΊΡΠ΅ΡΠΈΠΈ ΠΈΡ Ρ ΠΌΠΎΠ»ΠΎΠΊΠΎΠΌ. ΠΠΎΠ»ΠΎΡΠ½Π°Ρ ΠΆΠ΅Π»Π΅Π·Π° ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ ΠΎΠ³ΡΠΎΠΌΠ½ΡΠΌ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΠΎΠΌ, ΡΠ°ΠΊ ΠΊΠ°ΠΊ ΠΈΡΡ ΠΎΠ΄Π½ΠΎ ΠΏΡΠ΅Π΄Π½Π°Π·Π½Π°ΡΠ΅Π½Π° Π΄Π»Ρ ΡΠΈΠ½ΡΠ΅Π·Π° ΠΈ ΠΈΠ·Π²Π»Π΅ΡΠ΅Π½ΠΈΡ Π±ΠΎΠ»ΡΡΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° Π±Π΅Π»ΠΊΠ°. ΠΠΎΠ½ΡΠ΅ΠΏΡΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΊΠ°ΠΊ Π±ΠΈΠΎΡΠ΅Π°ΠΊΡΠΎΡΠ° ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΠΈΠΌΠ΅Π΅Ρ ΡΡΠ΄ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ² Ρ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ Π±ΠΈΠΎΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ: ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π½Π°ΡΠΈΠ²Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ², Π±ΠΎΠ»ΡΡΠΎΠΉ Π²ΡΡ ΠΎΠ΄, ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠΎΠΊΡΠΈΡΠ½ΡΡ ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ.
Π ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈΠ· ΠΏΡΡΠ΅ΠΉ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΡΠ°Π½ΡΠ³Π΅Π½Π° Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ -Π±ΠΈΠΎΡΠ΅Π°ΠΊΡΠΎΡΠΎΠ² ΠΏΡΠ΅Π΄Π»Π°Π³Π°Π΅ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ. Π’ΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΌΠΎΠΆΠ΅Ρ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΡΡΡΡ ΠΏΡΡΠ΅ΠΌ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠ΅ΡΠ΅Π· ΠΌΠΎΠ»ΠΎΡΠ½ΡΠΉ ΠΏΡΠΎΡΠΎΠΊ. ΠΠ΅ΡΡΠ½ΠΎΠ΅ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π½Π΅ΡΠ»ΠΎΠΆΠ½ΠΎΠΉ ΠΈ ΠΌΠ°Π»ΠΎΡΡΠ°Π²ΠΌΠ°ΡΠΈΡΠ½ΠΎΠΉ ΠΏΡΠΎΡΠ΅Π΄ΡΡΠΎΠΉ, ΠΊΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΠΎΠ½ΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠΎΠ·Π΄Π°ΡΡ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΡΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΠΈ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ ΠΏΠΎΡΠ΅ΡΠΈ, Π½Π΅ΠΈΠ·Π±Π΅ΠΆΠ½ΡΠ΅ ΠΏΡΠΈ ΡΠΈΡΡΠ΅ΠΌΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ.
Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΡΠΆΠ΅ΡΠΎΠ΄Π½ΠΎΠΉ ΠΠΠ Π² ΡΡΠΊΠ°ΡΠΈΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ (Yang, 1992; Desnick and Schuchman, 1998). Π ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΡΡΡΡ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΎΠ±Π»Π°ΡΡΠΈ ΡΠΈΡΡΠ΅ΠΌ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΠΠΠ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ , Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ — ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ. Π Π΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ Π΄ΠΎΡΡΠ°Π²ΠΊΠ° Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠΎΡΠ΅ΡΠ°Π΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π΄Π»Ρ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° ΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ, ΡΡΠΎ, Π² ΠΏΡΠΈΠ½ΡΠΈΠΏΠ΅, ΠΌΠΎΠΆΠ΅Ρ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΡΠΎΠ²Π°ΡΡ Π»ΡΠ±ΠΎΠΉ Π²ΡΠ±ΡΠ°Π½Π½ΡΠΉ ΡΠΈΠΏ ΠΊΠ»Π΅ΡΠΎΠΊ (Michael and Curiel, 1994; Guy et al. 1995). ΠΡΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ Π΄Π°Π΅Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠ°ΠΊΠΆΠ΅ Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΠΈ Π½Π΅Π΄Π΅Π»ΡΡΠΈΠ΅ΡΡ ΠΊΠ»Π΅ΡΠΊΠΈ. ΠΠ½ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π΄Π»Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ in vitro ΠΈ in vivo. ΠΠ°Π½Π½ΡΠΉ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π»Π΅Π³ΠΊΠΎ Π²Π°ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΠΈ Π·Π°ΠΌΠ΅Π½ΡΡΡ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π΄ΠΎΡΡΠ°Π²Π»ΡΠ΅ΠΌΡΠΉ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ Π°Π΄ΡΠ΅ΡΠ½ΡΠΉ Π»ΠΈΠ³Π°Π½Π΄. ΠΠ΅ΡΠΎΠ΄ Π½Π΅ Π½Π°ΠΊΠ»Π°Π΄ΡΠ²Π°Π΅Ρ ΡΡΡΠΎΠ³ΠΈΡ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½ΠΈΠΉ ΠΏΠΎ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ ΠΈ ΡΠ°Π·ΠΌΠ΅ΡΠ°ΠΌ ΠΌΠΎΠ»Π΅ΠΊΡΠ» ΠΠΠ. ΠΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΡ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ Π²ΡΠ΄Π΅Π»Π΅Π½Ρ (ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Ρ) ΠΈΠ»ΠΈ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ (Π±ΠΈΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΠ΅ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΡ) Π² Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅. ΠΠ»Ρ Π²Π½Π΅Π΄ΡΠ΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄Π° Π² Π±ΠΈΠΎΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π²Π°ΠΆΠ½ΡΠΌ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π·Π°ΠΊΠΎΠ½ΠΎΠΌΠ΅ΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΈ Π΅Π΅ ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ, ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ Π΄Π»Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ in vivo.
ΠΠΎΠ΄ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ²ΠΎΠΌ A.C. Π‘ΠΎΠ±ΠΎΠ»Π΅Π²Π° Π±ΡΠ»Π° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΡΠΈΡΡΠ΅ΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° Ρ ΠΈΠ½ΡΡΠ»ΠΈΠ½ΠΎΠΌ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π»ΠΈΠ³Π°Π½Π΄Π° (Π‘ΠΎΠ±ΠΎΠ»Π΅Π², 1988). ΠΡΠΎΡ ΠΏΠΎΠ΄Ρ ΠΎΠ΄ ΡΡΠΏΠ΅ΡΠ½ΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΡΡ ΠΏΡΠΈ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π³Π΅ΠΏΠ°ΡΠΎΠΌΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Π² ΠΊΡΠ»ΡΡΡΡΠ΅ (Π ΠΎΠ·Π΅Π½ΠΊΡΠ°Π½Ρ ΠΈ Π΄Ρ. 1990; Rosenkranz et al. 1992). ΠΡΡ ΠΎΠ΄Ρ ΠΈΠ· ΡΠΎΠ³ΠΎ, ΡΡΠΎ ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΎΠ±Π»Π°Π΄Π°ΡΡ ΠΈΠ½ΡΡΠ»ΠΈΠ½ΠΎΠ²ΡΠΌΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ (Burnol et al. 1990), ΠΈΠ½ΡΡΠ»ΠΈΠ½ Π±ΡΠ» Π²ΡΠ±ΡΠ°Π½ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π»ΠΈΠ³Π°Π½Π΄Π° Π΄Π»Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠΌΠ΅ΡΡΠ΅ΠΉΡΡ Π½Π° ΡΠ΅Π³ΠΎΠ΄Π½Ρ ΡΠΎΠ²ΠΎΠΊΡΠΏΠ½ΠΎΡΡΠΈ Π΄Π°Π½Π½ΡΡ Π½Π°ΠΌΠΈ Π±ΡΠ»Π° ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π° ΠΈΠ΄Π΅Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΠΆΠΈΠ²ΠΎΡΠ½ΠΎΠ³ΠΎ-Π±ΠΈΠΎΡΠ΅Π°ΠΊΡΠΎΡΠ° ΠΏΡΡΠ΅ΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ. Π ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΡΠΎΠΉ ΠΈΠ΄Π΅ΠΈ ΠΈ Π²ΡΠΏΠΎΠ»Π½ΡΠ»Π°ΡΡ Π΄Π°Π½Π½Π°Ρ ΡΠ°Π±ΠΎΡΠ°. 7.
Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ:
Π¦Π΅Π»ΡΡ Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ Π±ΡΠ»ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ΅Π»Π΅Π²ΡΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΌΠΎΠ»ΠΎΠΊΠΎΠΌ ΡΠ΅Π»ΡΡΠΊΠΎΡ ΠΎΠ·ΡΠΉΡΡΠ²Π΅Π½Π½ΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ .
ΠΠ»Ρ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠΊΠ°Π·Π°Π½Π½ΠΎΠΉ ΡΠ΅Π»ΠΈ Π±ΡΠ»ΠΈ ΠΏΠΎΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ»Π΅Π΄ΡΡΡΠΈΠ΅ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π·Π°Π΄Π°ΡΠΈ:
1. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΠΉ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ· ΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΉ ΡΡΠ°Π½ΡΠΏΠΎΡΡ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠ° ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½ ΠΈ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ Π΄Π°Π½Π½ΡΠΉ ΠΊΠΎΠ½ΡΡΠ³Π°Ρ, Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² ΠΊΡΠ»ΡΡΡΡΠ΅.
2. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΡ ΠΈ ΠΎΠΏΡΠΈΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ ΡΠΎΡΡΠ°Π² ΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π³ΠΎ ΡΡΠΎΠ²Π½Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π² ΠΊΡΠ»ΡΡΡΡΠ΅.
3. ΠΡΡΡΠ΅ΡΡΠ²ΠΈΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ Π΄ΠΎΡΡΠ°Π²ΠΊΡ ΡΠ΅ΠΏΠΎΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vivo.
4. ΠΡΠ΅Π½ΠΈΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½Π°, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅Π³ΠΎ ΡΠ΅ΠΊΡΠ΅ΡΠΈΡΡΠ΅ΠΌΡΠΉ Ρ ΠΌΠΎΠ»ΠΎΠΊΠΎΠΌ Π±Π΅Π»ΠΎΠΊ, Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vivo.
ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ.
Π§Π΅Π»ΠΎΠ²Π΅ΡΠ΅ΡΠΊΠΎΠ΅ Π·Π½Π°Π½ΠΈΠ΅ Π½Π΅ΠΈΠ·ΠΌΠ΅ΡΠΈΠΌΠΎ Π²ΠΎ Π²ΡΠ΅ ΡΡΠΎΡΠΎΠ½Ρ, ΠΈ ΠΈΠ· ΡΠΎΠ³ΠΎ, ΡΡΠΎ Π΄ΠΎΡΡΠΎΠΉΠ½ΠΎ Π·Π½Π°Π½ΠΈΡ, Π½ΠΈΠΊΡΠΎ Π² ΠΎΠ΄ΠΈΠ½ΠΎΡΠΊΡ Π½Π΅ ΠΌΠΎΠΆΠ΅Ρ Π·Π½Π°ΡΡ Π΄Π°ΠΆΠ΅ ΠΈ ΡΡΡΡΡΠ½ΠΎΠΉ Π΄ΠΎΠ»ΠΈ.
ΠΡΡΡΡ Π¨ΠΎΠΏΠ΅Π½Π³Π°ΡΡΡ «ΠΡΠΎΡΠΈΠ·ΠΌΡ ΠΈ ΠΌΠ°ΠΊΡΠΈΠΌΡ «.
Π ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π΄Π΅ΡΡΡΠΈΠ»Π΅ΡΠΈΡ ΠΏΠΎΠ»ΡΡΠΈΠ»ΠΈ ΡΠΈΡΠΎΠΊΠΎΠ΅ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΠΠΠ, Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΠΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡΠ°ΡΡΠΈΡ in vitro ΠΈ in vivo, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ Π²Π²Π΅Π΄Π΅Π½Π½ΡΡ Π³Π΅Π½ΠΎΠ². ΠΡΠΈ ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΠΏΡΠΈΠ²Π΅Π»ΠΈ ΠΊ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² Π±ΠΈΠΎΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ — Π΄Π»Ρ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠ²Π° Π±Π΅Π»ΠΊΠΎΠ² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π²Π°ΠΆΠ½ΠΎΡΡΠΈ, ΡΠ°Π½Π΅Π΅ ΠΏΠΎΠ»ΡΡΠ°Π΅ΠΌΡΡ ΠΈΠ· ΠΏΡΠΈΡΠΎΠ΄Π½ΡΡ ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², ΠΈ Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π΅ — Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΏΡΡΠ΅ΠΌ ΠΈΠ½ΡΡΠΎΠ΄ΡΠΊΡΠΈΠΈ Π½ΠΎΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠ΅ ΠΊΠ»Π΅ΡΠΊΠΈ Π±ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ° (Π³Π΅Π½Π½Π°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ).
ΠΠ΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΠΎ, ΡΡΠΎ ΠΊ Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½ΠΎ Π±ΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΡΠΆΠ΅ΡΠΎΠ΄Π½ΠΎΠΉ ΠΠΠ, ΠΏΡΠΎΠ±Π»Π΅ΠΌΠ° ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° ΠΠΠ in vivo ΠΎΡΡΠ°Π΅ΡΡΡ Π½Π΅ΡΠ΅ΡΠ΅Π½Π½ΠΎΠΉ (Yang, 1992; Desnick and Schuchman, 1998). Π‘ΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ ΡΡΠ΄ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ in vivo ΡΠ΅Ρ ΠΈΠ»ΠΈ ΠΈΠ½ΡΡ ΡΠΈΡΡΠ΅ΠΌ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ: 1) Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ — ΠΏΠΎΡΡΡΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΠΠ Π² ΠΈΠ·Π±ΡΠ°Π½Π½ΡΠΉ ΡΠΈΠΏ ΠΊΠ»Π΅ΡΠΎΠΊ/ΡΠΊΠ°Π½Π΅ΠΉ, 2) ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ, 3) ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΈ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΡ Π΄Π»Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°, 4) ΡΡΡΠΎΠΉΡΠΈΠ²ΠΎΡΡΡ ΠΏΡΠΈ Ρ ΡΠ°Π½Π΅Π½ΠΈΠΈ ΠΈ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌ, 5) ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ½ΠΎΡΡΡ ΠΈ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½Π°Ρ Π΄Π΅ΡΠ΅Π²ΠΈΠ·Π½Π° ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΠΈΠΊΠΎΠ² ΠΠΠ, 6) ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½ΠΈΠΉ ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠΈΠΌΠΎΠΉ ΠΠΠ. ΠΠ΅ΡΠΎΠ΄ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΎΠΌ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΠ΅Ρ ΡΡΠΈΠΌ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡΠΌ (Michael and Curiel, 1994; Guy et al. 1995). ΠΡΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ ΡΠΎΡΠ΅ΡΠ°Π΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π΅ΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π΄Π»Ρ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° ΠΈ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ, ΡΡΠΎ, Π² ΠΏΡΠΈΠ½ΡΠΈΠΏΠ΅, ΠΌΠΎΠΆΠ΅Ρ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΡΡΠ°Π½ΡΡΠ΅ΡΠΈΡΠΎΠ²Π°ΡΡ Π»ΡΠ±ΠΎΠΉ Π²ΡΠ±ΡΠ°Π½Π½ΡΠΉ ΡΠΈΠΏ ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠ½ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π΄Π»Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ in vitro ΠΈ in vivo. Π Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ Π²ΠΎ ΠΌΠ½ΠΎΠ³ΠΈΡ Π½Π°ΡΡΠ½ΡΡ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΡΡ ΠΈΠ΄Π΅Ρ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½Π°Ρ ΡΠ°Π±ΠΎΡΠ° ΠΏΠΎ ΠΏΡΠ΅Π²ΡΠ°ΡΠ΅Π½ΠΈΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠ΅ΠΉ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° Π² ΡΠ΅Π°Π»ΡΠ½ΡΠΉ Π²ΡΡΠΎΠΊΠΎΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΡΠΏΠΎΡΠΎΠ± Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π³Π΅Π½ΠΎΠ² in vivo.
ΠΡΠ²ΠΎΠ΄Ρ.
1. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΠ΅ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠ΅ ΠΈΠ½ΡΡΠ»ΠΈΠ½-ΠΏΠΎΠ»ΠΈΠ»ΠΈΠ·ΠΈΠ½, ΠΎΠ±Π΅ΡΠΏΠ΅ΡΠΈΠ²Π°ΡΡ ΡΡΠ°Π½ΡΠΏΠΎΡΡ ΠΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠΈ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΌΡΡΠΈ Π»ΠΈΠ½ΠΈΠΈ ΠΠ‘-11 ΡΠ΅ΡΠ΅Π· ΠΈΠ½ΡΡΠ»ΠΈΠ½ΠΎΠ²ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ. Π£ΡΠΏΠ΅ΡΠ½ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² ΠΊΡΠ»ΡΡΡΡΠ΅.
2. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅ Π°Π΄Π΅Π½ΠΎΠ²ΠΈΡΡΡΠΎΠ² ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΈ ΠΏΡΠΈΡ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² Π² ΡΠΎΡΡΠ°Π² ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΠΈ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ°Ρ ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΠ°ΠΊΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ Π»ΠΈΠ½ΠΈΠΈ ΠΠ‘-11 Π±ΠΎΠ»Π΅Π΅ ΡΠ΅ΠΌ Π½Π° 3 ΠΏΠΎΡΡΠ΄ΠΊΠ°. ΠΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½Π°Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΠΏΠΎΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° Π½Π°Π±Π»ΡΠ΄Π°Π΅ΡΡΡ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΡΠΌΠΈ Ρ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ΠΌ Π»ΠΈΠ·ΠΈΠ½/Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ ΠΎΡ 2 Π΄ΠΎ 4, ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π°/Π²ΠΈΡΡΡ ΠΎΡ 4 Π΄ΠΎ 10.
3. ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½Π°Ρ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΡ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ in vivo ΠΏΡΡΠ΅ΠΌ ΠΌΠ΅ΡΡΠ½ΠΎΠ³ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ. ΠΠΎΠ»ΡΡΠ΅Π½Ρ Π΄Π°Π½Π½ΡΠ΅ ΠΎΠ± ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΠΠΠ in vitro ΠΈ in vivo.
4. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π° Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΅ΠΏΠΎΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠΏΠΈΡΠ΅Π»ΠΈΡ ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ Π² ΠΊΡΠ»ΡΡΡΡΠ΅, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· ΠΌΡΡΠ΅ΠΉ ΠΈ ΠΎΠ²Π΅Ρ.
5. ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π½Π° ΠΏΡΠΈΠ½ΡΠΈΠΏΠΈΠ°Π»ΡΠ½Π°Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΊΡΠ΅ΡΠΈΡΡΠ΅ΠΌΡΡ Π±Π΅Π»ΠΊΠΎΠ² Ρ ΠΌΠΎΠ»ΠΎΠΊΠΎΠΌ ΡΠ΅Π»ΡΡΠΊΠΎΡ ΠΎΠ·ΡΠΉΡΡΠ²Π΅Π½Π½ΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΡΡΠ΅ΠΊΡΠΈΠΈ ΠΌΠΎΠ»ΠΎΡΠ½ΡΡ ΠΆΠ΅Π»Π΅Π· ΠΏΡΠΈ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΠΠ-ΠΏΠ΅ΡΠ΅Π½ΠΎΡΡΡΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ ΡΠ΅ΡΠ΅Π· ΠΌΠΎΠ»ΠΎΡΠ½ΡΠΉ ΠΏΡΠΎΡΠΎΠΊ.
Π‘ΠΏΠΈΡΠΎΠΊ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
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- ΠΡΡΠ°ΠΆΠ°Ρ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΡ Π½Π°ΡΡΠ½ΠΎΠΌΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ — ΠΏΡΠΎΡΠ΅ΡΡΠΎΡΡ, Π΄ΠΎΠΊΡΠΎΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π½Π°ΡΠΊ ΠΠ»Π΅ΠΊΡΠ°Π½Π΄ΡΡ Π‘Π΅ΡΠ³Π΅Π΅Π²ΠΈΡΡ Π‘ΠΎΠ±ΠΎΠ»Π΅Π²Ρ Π·Π° ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ°Π±ΠΎΡΠ°ΡΡ Π½Π°Π΄ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ΅ΠΌΠΎΠΉ Π² Π±ΠΈΠΎΡΠΈΠ·ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΈ ΠΏΠΎΠ΄ Π΅Π³ΠΎ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ²ΠΎΠΌ.
- Π’Π°ΠΊΠΆΠ΅ Π²ΡΡΠ°ΠΆΠ°Ρ Π±Π»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΡ Π²ΡΠΎΡΠΎΠΌΡ Π½Π°ΡΡΠ½ΠΎΠΌΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π½Π°ΡΠΊ ΠΠ½Π΄ΡΠ΅Ρ ΠΠ»Π΅ΠΊΡΠ°Π½Π΄ΡΠΎΠ²ΠΈΡΡ Π ΠΎΠ·Π΅Π½ΠΊΡΠ°Π½ΡΡ Π·Π° ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΡΡ ΡΠ°Π±ΠΎΡΡ, Π·Π° Π½Π΅ΠΎΡΠ΅Π½ΠΈΠΌΡΡ ΠΏΠΎΠΌΠΎΡΡ Π² ΠΏΠ»Π°Π½ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠΎΠ² ΠΈ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ.
- ΠΡΠ΅Π½Ρ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π»ΡΠ½Π° ΠΠ»Π°Π΄ΠΈΠΌΠΈΡΡ ΠΡΠ°Π½Π°ΡΡΠ΅Π²ΠΈΡΡ ΠΠΈΠΊΠΈΡΠΈΠ½Ρ Π·Π° ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΡΡ ΡΠ°Π±ΠΎΡΡ Ρ ΠΆΠΈΠ²ΠΎΡΠ½ΡΠΌΠΈ ΠΈ Π’Π°ΡΡΡΠ½Π΅ ΠΡΠΈΠ³ΠΎΡΡΠ΅Π²Π½Π΅ ΠΠΈΡΠ΅Π»Π΅Π²ΠΎΠΉ Π·Π° Π²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΊΡΠ»ΡΡΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ, Π° ΡΠ°ΠΊΠΆΠ΅ Π²ΡΠ΅ΠΌ ΡΠΎΡΡΡΠ΄Π½ΠΈΠΊΠ°ΠΌ Π±ΠΈΠΎΡΠΈΠ·ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ Π·Π° ΠΏΠΎΠΌΠΎΡΡ ΠΈ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΡ.