Kusanthula kwamiyala yam'madzi (kuwunika kwa CSF) ndi kukhazikika kwa matrix: Kuthetsa mabotolo aluso a matracy mu CNS mankhwala a Bioanalysis

1 Iphase Zinthu

2 Zakuthupi Zam'mimba zamadzimadzi: Bionalysis of Hubongo

Ubongo umagawidwa m'magawo anayi, kuphatikizapo TVAnphalon, dientphalon, cerebellum, ndi brainstem. Zingwezo m'magawo osiyanasiyana a ubongo zimatchedwa mancricles, omwe amadzazidwa ndiufa (CSF). Mafuta a minyewa amaphatikizidwa makamaka pakugawidwa ndi kagayidwe ka mankhwala mu ubongo ndi dongosolo lamanjenje lamphamvu (CNS).

Pharmacondynamics imawerengera mphamvu zoyaka mankhwala osokoneza bongo, kugawa, komanso mawu m'thupi kudzera pakuwunika kwa kuchuluka, kuwonetsera kuchuluka kwa mankhwala osokoneza bongo, poyang'ana magazi. Mwazi - chotchinga cha ubongo (BBB) ​​ndi mawonekedwe osinthana ndi kusankha, zomwe zimalepheretsa kugawa zinthu zoyipa ndi magazi mu Morestyma. Kusintha kwa BBB Kungogwiritsa ntchito mankhwala osokoneza bongo ngati chizindikiro choloweza kwa mankhwala osokoneza bongo a mankhwalawa kungayambitse kuchuluka kwa zinthuzo, ndipo pamakhala chiopsezo chosokoneza zinthu zomwe sizimachitika chifukwa cha zomwe sizimachitika chifukwa cha vuto la ubongo. Chifukwa chake, pamlingo wa macro, bongo la ubongo homogenization kapena njira zamadzimadzi zimagwiritsidwa ntchito makamaka pamagawo a pharmacokinetic.

3 Kutanthauza kwa Madzi a Timerbrospinal Kusanthula Kupanga Mankhwala

Mapuloteni omwe ali csf ali otsika kwambiri, ndipo ndende yake yosiyanasiyana imagwiritsidwa ntchito ngati chizindikiro choloweza kwa ma cn free mankhwala. Komabe, kugwira ntchito kwa CSF kumachepetsa kwambiri kuposa kufalikira kwa magazi, zomwe zimapangitsa kusakaniza kosakwanira kwa zomwe zili mu CSF. Kutengera ndi malo a Sampling / Nthawi ndi nthawi ndi oyang'anira, mankhwalawa ku CSF akhoza kukhala osiyanasiyana.Madzi a Mlanduwo (opanga csf, ACSF) ndi njira yothetsera kapangidwe kake ndi ntchito yamadzimadzi, ndipo imatha kuwunika molondola CNS Fevermacokinetic deta mu vitro adme. Kuphatikiza apo, nsomba zamadzi zongopeka zimatha kugwiritsidwanso ntchito poyesa zotsatira zake za edema ndi mapuloteni apadera.

4 Zovuta Za Mutuping Strarksination ndi kufunika kwa matrix opanda kanthu

4.1 Makhalidwe / Zofooka Zachipatala Zopezera Madzi Achilengedwe

Kupeza kwa madzi amtundu wachilengedwe amayang'anizana ndi mabotolo amphamvu. Anthu athanzi amafunika kupeza madzi amchere kudzera mu khwangwala kapena ngalande yamagetsi, zomwe zimapangitsa kuti zikhale zovuta kuchita zodzipereka. Kugwiritsa ntchito madzi am'madzi am'madzi /Mafuta a ChiedrosPal(opanga csf /Zoyeserera CSF)) Matrix m'malo mwa zitsanzo zachilengedwe za kukhathamiritsa, kupewa nkhani zamakhalidwe, ndikuwonetsetsa kusanthula kotheratu ndikusunga matrin mivi (monga ma elekitirolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte ndi electrolyte

4.2 zotsatira za matrix zomwe zimachitika chifukwa chosiyana

Mitunduyo / kusiyana pakati pa mapuloteni (15 - 100 mg / dl), phospholipos, ndi zinthu zam'madzi zomwe zimapangitsa ion incrostery / MS / MS / MS / MS Mwa kusintha mapangidwe a nsomba zamadzimadzi / zowoneka bwino zamadzimadzi / miyala yamitundu yosiyanasiyana, LC - MS Technology ya MS / MS / MS / MS / MS / MS Trawalogy imagwiritsidwa ntchito kukhazikitsa kusiyana. Ndikothekanso kusintha gawo lam'manja (monga hilic chromatography) kapena kuwonjezera nthawi yosungirako kuti idule zinthu zomwe matrix zimasokoneza.

4.3 Kusintha kwa kusintha kwa matrix zachilengedwe pa kusanthula pansi pa matenda

Matenda a strabrospinal amakhoza kukhala ndi mapuloteni achilendo (monga kuchepa kwa Taun), magazi - zotchinga zotchinga (Il - 6), ms / ms.

5 Cross Center Strabrospinal Dybrinal

5.1 Madzi a Celbrospinal(CSF yamunthu)

Madzi amtundu waumunthundi matrabspinal agolide am'madzi am'madzi, koma malire olakwika amatsogolera ku kuchepa kwachilengedwe; Mapuloteni otsika (15 - 45 mg / dl), maselo otsika a cell, amafunikira LC - Ms / MS, a β, Tau).

5.2 Cynomolgus Monkey Strabrossinal Madzi (Monkey CSF / NHP CSF)

Nsomba za cynomolgusndi omwe ali - mtundu wa anthu oyandikira kwambiri kwa anthu, okhala ndi kusiyana kochepa, ndikoyenera kuwunika kwa PK / PD ndi chitetezo chamankhwala osokoneza bongo, ndipo ndi mtundu womwe umakonda kuwerengera kafukufuku wa mankhwala ambiri a CNS.

5.3 Ruthes Monkey Strabylospinal flebrossinal madzi (Monkey CSF / NHP CSF)

Madzi a Monkes Monkeyikuyerekezeredwa ndi nyani ya cynomolgus, ili ndi mawonekedwe a neuroimmune a neuroimmune ndipo ndioyenera kwambiri matenda ofananira ndi matenda a neurophicemfphintim minoinfphintim minofu kapena mankhwala owongolera.

5.4 Ku Beagle Gagle Sterbrospinal flebrospinal madzi (Begagle galu csf)

Mlandu wa BegralNdilokha mtundu wa protecan wamkulu, womwe ndi woyenera kuwunika magazi - chotchinga cha ubongo komanso kuphunzira zamankhwala zamankhwala zamankhwala.

5.5 SD JAT STRBROWINA DZIKO (Rat csf)

Sd cut cellbrospinal madziNdi ya madzi ang'onoang'ono a strabrospinal madzi osinthika - Kupuma kwapamwamba - mtengo wotsika komanso kuchuluka kwa maji, omwe amagwiritsidwa ntchito kwambiri pophunzira zamankhwala a mitsempha.

5.6 mbewa yopanda madzi (Mbewa csf)

Mbewa zamadzimadzindichinthu chofunikira kwambiri pakufufuza za neuroscios, makamaka kugwiritsidwa ntchito kwambiri mwa gene kusinthidwa mitundu mitundu (monga matenda a Alzheimer, matenda a Parminson) ndi Center.

5.7 minipig cellbrospinal madzi (Minipig csf)

Mimba madzi a minipig 'Katundu wa onatomical amalola kusamba mobwerezabwereza, ndikupangitsa kukhala koyenera kwa nthawi yayitali - Kafukufuku wamakampani. Komabe, kapangidwe kake kwa phospholipids kumasiyana kwambiri ndi kwa anthu, ndipo kusankhidwa kwa njirayi ayenera kutsimikiziridwa.

5.8 kalulu wa kalulu wa kalulu (Kalulu CSF)

Kalulu CSF Ndi imodzi mwazomwe zimagwiritsidwa ntchito kawirikawiri m'mafufuzidwe a neuroscience, makamaka mankhwala opha ophthalmi, makamaka masheya (a CLB), zotchinga za BBB)

Mapeto

Kusanthula kwamadzimadzi madzi (CSF) kumasewera gawo lofunika kwambiri dongosolo (CNS) Kukula kwa mankhwala (CN) Kukula kwa mankhwala osokoneza bongo, zotchinga zaubongo (Bbb) mu chapakati mantha dongosolo. Komabe, kugwiritsa ntchito ma csf zachilengedwe kumakumana ndi zovuta zazikulu, kuphatikizapo zovuta zamakhalidwe osonkhanitsidwa, kuphatikiza mitundu ndi pakati pazinthu za matrix, ndikusintha mbiri zamakono m'magazi. Zofooka izi zimatsimikizira kufunika kwa matricts acf, omwe amathandizira pakusintha kwa bioanalytical pomwe akusintha mapangidwe a zinthu komanso aluso.

LC - MS / MS yatulukira ngati chida chofunikira kwambiri cha maphunziro a CSF, kupereka chidwi kwambiri ndi kuchuluka kwa mankhwala osokoneza bongo ndipo biomarkers pamalo otsika. Komabe, matrix zotsatira-zoyendetsedwa ndi kusiyana kwa mapuloteni, lipid, ndi electrolyte zomwe zilimo, zimafunikira kukhathamiritsa mosamala kwa kukonzekera kwa zitsanzo. Ma metric Materi a CSF, ogwirizana ndi mizimu yathanzi komanso yathanzi (mwachitsanzo.

Pakati pa mitundu ya zinyama, cynomolgus csf amafanana kwambiri ndi CSF ndipo amakonda kwambiri kafukufuku wa PK / PD. Modent Models (E.g., SD Makoswe) Mtengo Wokwera - Zothandiza - Zowonjezera - Mimba CSF imalola kuti mubwereze mobwerezabwereza - Maphunziro a mawu.

Pomaliza, kuphatikiza kwa mitundu - Materi a CSF ojambula omwe ali ndi LC / MS Memologies amalankhula mabotolo a mankhwala osokoneza bongo a CNS Kukula kwa mtsogolo kuyenera kuyang'ana kwambiri pa mitundu yoyenga kwa matenda a CSF ndikukonzanso ma bionalytical kuti mulosere bwino zotsatira zamankhwala.

Mawu ofunikira: Mafuta am'madzi, ma cellbrospinal madzimadzi, ma csf, omangika a csf, csf crebrosgus madzimadzi (csfs csf, agalu a Beagle) Mafuta am'madzi, galugle galu csf, st crebrospinal madzi, mbewa csf, minipig csft, kalulu csbrospinal madzimadzi, chiwonetsero cha CSF

Cite: Ban Wei - Kang, Yang Zhi - Hong. Njira Zofufuzira ndi Tekisirier Templeoloje akupita ku ma entracerreral amachiritso. Chinese phalacactin, 2023, 39 (9): 1607 - 1612.