Na Cocer Peptides 
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INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake
Thymosine Alpha-1 (Tα1) ni peptide ifite imikorere ikomeye yubudahangarwa bw'umubiri. Yabanje kwitandukanya na thymus tissue kandi igizwe na acide 28 amine, hamwe na N-terminal acetylation. Tα1 igira uruhare runini mukubungabunga ubudahangarwa bw'umubiri no guhangana n'indwara z'umubiri. Nukongera ubudahangarwa bw'umubiri, byerekana imbaraga zikomeye zo gukoreshwa mukuvura no gukumira indwara zitandukanye.
Igishushanyo 1 Thymosine alpha 1 ifite ibikorwa byinshi byibinyabuzima. IL: Interleukin; IFN: Interferon; TLR: Kwakira bisa.
Mugihe cyimiterere yumubiri, Tα1 igira uruhare mukiterambere risanzwe no kubungabunga imikorere yubudahangarwa bw'umubiri, bigira uruhare runini mu gutandukanya, gukura, no gukora ingirabuzimafatizo. Mu bihe by’indwara, nk'indwara ziterwa na virusi, tumorigenez, hamwe n’ubudahangarwa bw'umubiri, Tα1 irashobora gufasha umubiri kurwanya indwara mu kugenzura ubudahangarwa bw'umubiri.
Mu rwego rw'indwara zandura virusi, Tα1 ikunze gukoreshwa mu kuvura virusi ya hepatite B (HBV) na virusi ya hepatite C (HCV). Irashobora kugenga imikorere yubudahangarwa, gufasha umubiri mugukuraho virusi, no kunoza imiterere yabarwayi.
Uburyo bwo gukingira indwara
(1) Imikoranire hamwe na Toll-imeze nk'iyakira (TLR)
Inzira imwe y'ingenzi inyuramo Tα1 ikoresha ingaruka zayo zo kwirinda indwara ni uguhuza na Toll-reseptors (TLRs). TLRs ni icyiciro cyo kumenyekanisha imiterere yerekana imiterere ya molekile ifitanye isano na virusi (PAMPs) hamwe na molekuline yangiza (DAMPs), bityo igakora selile yumubiri kandi igatangiza ibisubizo byubudahangarwa.
Tα1 irashobora guhuza TLR nyinshi, nka TLR3, TLR4, na TLR9. Iyo uhambiriye kubakira, Tα1 ikora inzira yerekana ibimenyetso byerekana inzira, harimo na interferon igenga ibintu 3 (IRF3) hamwe nibintu bya kirimbuzi κB (NF-κB) byerekana inzira. Dufashe urugero rwa TLR3, nyuma yuko Tα1 ihujwe na TLR3, iteza imbere fosifora ya IRF3, hanyuma igahinduka muri nucleus selile, bigatuma habaho imvugo ya virusi ya virusi na immunite igenga ubwoko bwa I interferon (IFN-I). IFN-I ifite ibikorwa byinshi bya virusi na immunite-bigenga, byongera umubiri kurwanya virusi.
Kuri TLR4, guhuza Tα1 bisa nkibikorwa bya NF-κB byerekana inzira, bikagaragaza imvugo ya cytokine ikongora nka tumor necrosis factor-α (TNF-α) na interleukin-6 (IL-6). Iyi cytokine igira uruhare runini mugihe cyambere cyo gukingira indwara, kwinjiza ingirabuzimafatizo aho zanduye no kongera ubushobozi bwo kwirinda umubiri.
Byongeye kandi, TLR2 na TLR7 nabyo bifitanye isano na Tα1. Tα1 irashobora gukora TLR2 / NF-κB, TLR2 / p38 mitogen-ikora protein kinase (p38MAPK), cyangwa TLR7 / myeloid itandukanya ibintu 88 (MyD88) byerekana inzira, bigateza imbere umusaruro wa cytokine zitandukanye nka IL-1 na IL-12, bityo bikarushaho kongera imbaraga zo gukingira indwara.
(2) Ingaruka zigenga ingirabuzimafatizo
T selile
Tα1 igira uruhare mu iterambere, gutandukanya, no gukora selile T. Muri thymus, Tα1 yihutisha kuzura no gukura kwa thymocytes. Ubushakashatsi bwerekanye ko nyuma yo guhagarika umusaruro wa T-selile yunganirwa na antibody mu mbeba ukoresheje 5-fluorouracil (5-FU), TIM1 ikomatanya imiti ishobora kugarura ubwo bushobozi bwo gukora antibody, kandi ikerekana ibikorwa ndetse no ku kigero gito cya 30 μg / kg.
Isesengura rya cytometrie ryerekanye ko iyi dose ya Tα1 yihutisha kuzura no gukura kwa thymocytes; icyakora, ntabwo bigira ingaruka kumvugo ya Smoothened (Smo), urufunguzo rwingenzi rutunganya inzitiramubu (Hh) yerekana inzira muri CD4⁻CD8⁻ thymocytes. Ibi birerekana ko Tα1 ishobora guteza imbere T selile ikuze binyuze munzira zerekana ibimenyetso byambukiranya cyangwa bigenga inzira ya Smo.
Kubireba T selile ikuze, Tα1 irashobora kugenga uburinganire bwa T selile. Muri microen ibidukikije yibibyimba, Tα1 irashobora guhindura igipimo cya selile CD8⁺ T hamwe na selile T igenga (Tregs) muguhindura itandukaniro rya selile dendritic (DC) no kwerekana imiterere ya chemokine, bityo bikongerera umubiri imbaraga zo kwirinda indwara.
Igishushanyo 2 Thymosine α1 (Tα1) irinda kwangirika kwa epiteliyale muri DSS hiyongereyeho na kolite irwanya CTLA-4 - iterwa na kolite.
Ingirabuzimafatizo B.
Nubwo ubushakashatsi butaziguye ku ngaruka za Tα1 kuri selile B ari gake cyane, ubushakashatsi buriho bwerekana ko bushobora kugira uruhare rutaziguye imikorere ya selile B igenga selile T. Kubera ko T selile igira uruhare runini mubikorwa byingirabuzimafatizo ya B, guhinduranya ibyiciro bya antibody, no gukura kwa affinity, amabwiriza ya Tα1 agenga imikorere ya T selile arashobora kugira uruhare rutaziguye ku musemburo wa antibody B, bityo bikongerera umubiri imbaraga zo gukingira umubiri.
Makrophage
Tα1 ifite kandi ingaruka zingenzi zigenga imikorere ya macrophage. Ukoresheje ubushakashatsi bwa MTT, byagaragaye ko Tα1 igaragaza ingaruka za cytotoxic kuri macrophage ya RAW 264.7, hamwe na kimwe cya kabiri ntarengwa cyo guhagarika (IC50) cya 368.105 μg / ml. Mugihe intumbero ya Tα1 yiyongera, ingaruka za cytotoxic kuri selile RAW 264.7 zirakomera, bigatuma kugabanuka kwingirabuzimafatizo.
Tα1 irerekana kandi ingaruka zo kurwanya inflammatory, zapimwe no gusesengura umusaruro wa nitric oxyde (OYA) muri selile RAW 264.7. Ibisubizo byerekanye ko murwego rwo hagati ya 7.813–31.25 μg / ml, NTA musaruro mu itsinda ryavuwe na Tα1 wagabanutse muburyo buterwa na dose ugereranije nitsinda rishinzwe kugenzura, byerekana ko Tα1 ishobora kugira ingaruka zayo zo kurwanya inflammatory ibuza NTA musaruro muri macrophage, bityo bikagenga ibisubizo byubudahangarwa bw'umubiri.
Ingirabuzimafatizo zica (selile NK)
Tα1 iteza imbere ikwirakwizwa rya selile ya NK no gukora, byongera ibikorwa bya cytotoxic. Ingirabuzimafatizo za NK ni kimwe mu bintu by'ingenzi bigize ubudahangarwa bw'umubiri, bushobora kudashobora kwica udukoko twanduye virusi na selile. Tα1 yongerera ubushobozi bwo kumenya no kwica ingirabuzimafatizo muguhuza imvugo yakira reseptor yibikorwa hejuru ya selile NK, bityo ikagira uruhare runini mukwandura virusi ndetse nubudahangarwa bwa antitumor.
(3) Amabwiriza y'urusobe rwa cytokine
Tα1 ikora imirimo yayo yo gukingira igenga urusobe rwa cytokine. Cytokine ni urwego rwa poroteyine ntoya ziva mu ngirabuzimafatizo hamwe na selile zimwe na zimwe zidafite ubudahangarwa, zitanga amakuru hagati ya selile kandi zikagenga imikorere y’uturemangingo ndetse n’uburemere nubwoko bwibisubizo by’ubudahangarwa.
Tα1 irashobora guteza imbere umusaruro wa cytokine zitandukanye, nka interleukin-2 (IL-2), interleukin-3 (IL-3), na interferon-γ (IFN-γ). IL-2 ni ikintu cyingenzi cyo gukura kwa T giteza imbere gukwirakwiza T selile no gukora, kongerera imbaraga ingirabuzimafatizo za NK na cytotoxic T lymphocytes T (CTLs), bityo bikazamura ubushobozi bwo kwirinda umubiri. IL-3 iteza imbere no gutandukanya ingirabuzimafatizo zitandukanye za hematopoietic stem selile na progenitor, zifasha kugumana ingirabuzimafatizo n'imikorere ya sisitemu y'umubiri. IFN-γ ifite imirimo myinshi, harimo antiviral, antitumor, hamwe ningaruka zogukingira indwara, kuzamura ubushobozi bwa fagocytic na cytotoxic ya macrophage, guteza imbere itandukaniro rya selile Th1, no kugenzura ubudahangarwa bw'umubiri bugana ku cyerekezo cy’ubudahangarwa bw'umubiri.
Byongeye kandi, Tα1 irashobora kugenga uburinganire hagati ya porotokore na anti-inflammatory cytokine. Mugihe cyo gusubiza umuriro, Tα1 irashobora guhagarika umusaruro mwinshi wa cytokine itera inflammatory nka TNF-α na IL-1, mugihe iteza imbere umusaruro wa cytokine anti-inflammatory nka interleukin-10 (IL-10), bityo bikagabanya ibyangiritse biterwa numubiri utera umubiri no gukomeza kuringaniza umubiri.
Ingaruka zongera ubudahangarwa
(1) Indwara ya virusi
Indwara ya Hepatite B na Hepatite C.
Tα1 igira uruhare runini mu kuvura indwara ya hepatite B na hepatite C. Ku ndwara ya virusi ya hepatite B idakira (HBV), Tα1 irashobora kugenzura imikorere y’umubiri kandi ikongerera ubushobozi bwo gukuraho HBV. Tα1 ikora ingirabuzimafatizo nka selile T na selile NK, ibafasha kumenya neza no kurandura selile zumwijima zanduye HBV. Tα1 irashobora kugenga urusobe rwa cytokine, igateza imbere umusaruro wa cytokine ya virusi nka IFN-γ no kubuza kwigana HBV.
Mu kuvura virusi ya hepatite C (HCV), Tα1 nayo igaragaza ingaruka nziza. Irashobora kongera ubudahangarwa bw'umubiri, gufasha mukurandura HCV, no kwerekana ingaruka zoguhuza iyo ikoreshejwe hamwe nindi miti igabanya ubukana bwa virusi, bityo igatera imbere intsinzi.
Izindi ndwara zandura
Usibye HBV na HCV, Tα1 irashobora no kugira uruhare mu zindi ndwara zandura virusi. Tα1 irashobora gufasha kunoza imenyekanisha ryabarwayi barembye cyane bafite COVID-19. Mugukosora ibyangiritse biterwa na lymphocyte immunite ikabije no kwirinda gukora T-selile ikabije, Tα1 irashobora kugabanya ibimenyetso byumurwayi no kuzamura imibereho.
(2) Amabwiriza yubudahangarwa no kurwanya umuriro
Kugena Impirimbanyi
Tα1 igira uruhare runini mugukomeza kuringaniza umubiri. Muri leta zidafite ubudahangarwa bw'umubiri, Tα1 irashobora guteza imbere ikwirakwizwa no gutandukanya ingirabuzimafatizo, bigarura imikorere yumubiri. Kurugero, mu ndwara zimwe na zimwe ziterwa no kubura ubudahangarwa bw'umubiri cyangwa leta zandujwe n'ubudahangarwa ziterwa na chimiotherapie cyangwa imiti ivura imirasire, Tα1 irashobora gufasha umubiri kugarura ubudahangarwa bw'umubiri mu kugenzura iterambere n'imikorere by'uturemangingo.
Mu ndwara ziterwa na autoimmune, Tα1 irashobora guhagarika ubudahangarwa bukabije bwumubiri kandi ikagabanya kwangirika kwa autoimmune muguhindura ibikorwa byingirabuzimafatizo hamwe numuyoboro wa cytokine.
Ingaruka zo kurwanya inflammatory
Tα1 ifite ingaruka zo kurwanya inflammatory. Mugihe cyo gusubiza, Tα1 irashobora kugenga imvugo ya cytokine iterwa no gutwika kandi ikabuza gukabya gukabije. Nkuko byavuzwe haruguru, Tα1 irashobora kubuza NTA musaruro muri macrophage, kugabanya imvugo ya cytokine itera inflammatory nka TNF-α na IL-1, kandi icyarimwe igateza imbere umusaruro wa cytokine irwanya inflammatory nka IL-10.
Igishushanyo cya 3 Nitric oxyde irekuwe nyuma yo kuvurwa hamwe na LPS hamwe nubushuhe butandukanye bwa Tα-1 muri selile RAW 264.7.
Muburyo bwububabare bukabije, Tα1 igabanya ubukana bwa allodynia na hyperalgesia iterwa na progaramu ya Freund yuzuye (CFA), ikanagabanya igenzura ryabunzi batera nka IFN-γ, TNF-α, hamwe nubwonko bukomoka mu bwonko (BDNF) buterwa na CFA. Byongeye kandi, Tα1 irashobora kugenga inzira ya Wnt3a / β-catenin yerekana inzira yinzira yumugongo, ikora mugihe cyo kubabara, kandi Tα1 irashobora guhindura imikorere yayo, bityo bikagabanya ububabare bukabije.
Amavuriro
(1) Kuvura Hepatite ya virusi
Mu kuvura kwa hepatite ya virusi, Tα1 yakoreshejwe cyane. Ku barwayi barwaye hepatite B idakira, ubushakashatsi bwinshi bw’amavuriro bwerekanye ko Tα1 ihujwe na nucleoside (aside) igereranya cyangwa ivura interferon igera ku kigero cyo hejuru cya HBV ADN ya serokonversion, HBeAg seroconversion, na ALT isanzwe ugereranije na monotherapy. Mu bigeragezo bimwe na bimwe by’amavuriro, guhuza Tα1 na entecavir mu kuvura abarwayi ba hepatite B idakira byaviriyemo umuvuduko mwinshi wa serokonversion ya ADN ya HBV nyuma y’ibyumweru 48 bivurwa ugereranije n’itsinda rivuwe na entecavir yonyine, kandi igipimo cya seroconversion ya HBeAg nacyo cyateye imbere.
Mu kuvura indwara ya hepatite C, Tα1 ihujwe n’imiti igabanya ubukana bwa virusi itera SIDA (DAAs) irashobora kongera imbaraga za virusi, cyane cyane ku barwayi ba hepatite C idashobora kwivuza, bishobora kuzamura igipimo cy’ubuvuzi.
(2) Kuvura indwara ziterwa na immunodeficiency
Ku ndwara zimwe na zimwe zambere zo gukingira indwara, nka hypoplasia ivuka, Tα1 irashobora gukoreshwa murwego rwo kuvura ubundi buryo. Nubwo Tα1 idashobora gukiza burundu izo ndwara, irashobora kugenga imikorere yubudahangarwa, kongera ubudahangarwa bw’abarwayi, kugabanya inshuro n’uburemere bw’indwara, no kuzamura imibereho y’abarwayi.
Indwara zabuze ubudahangarwa bw'umubiri, nka VIH / SIDA, Tα1 zifatanije no kuvura virusi itera SIDA (ART) zirashobora kongera imbaraga mu kongera ubudahangarwa bw'umubiri, kongera umubare w'uturemangingo twa CD4⁺ T, kunoza imikorere y’umubiri, no kugabanya ubwandu bw’amahirwe.
(3) Ibindi Porogaramu
Ubuvuzi bwa Adjuvant kuburwayi bwanduye
Mu kuvura indwara zikomeye nka sepsis, Tα1 irashobora gukoreshwa nkumuti wongeyeho. Abarwayi ba Sepsis bakunze kugira imikorere mibi. Tα1 igenga imikorere yimikorere yumubiri hamwe numuyoboro wa cytokine, ifasha kugarura uburinganire bwumubiri, kugabanya ibisubizo byumuriro, no kuzamura imibereho yabarwayi.
Mu kuvura indwara zandura zidakira nk'igituntu, Tα1 ifatanije n'imiti igabanya ubukana irashobora kongera ubushobozi bw'umubiri bwo kurwanya indwara y'igituntu cya Mycobacterium no kunoza uburyo bwo kuvura.
Indwara ziterwa no gutwika
Mu kuvura indwara ziterwa no gutwika nka rubagimpande ya rubagimpande nindwara zifata amara, ingaruka za Tα1 zo kurwanya no gukingira indwara zishobora kugira agaciro gakoreshwa. Nubwo gukoresha amavuriro ari bike, ubushakashatsi bwibanze hamwe n’ibigereranyo bito by’amavuriro byagaragaje ko Tα1 ishobora kugabanya ibisubizo by’umuriro no kunoza imiterere y’abarwayi igenga ingirabuzimafatizo na cytokine.
Umwanzuro
Thymosine α1 (Tα1), nka peptide ifite imiterere yongera ubudahangarwa bw'umubiri, yerekanye ingaruka nini kandi zimbitse mu rwego rwo kugenzura ubudahangarwa bw'umubiri. Uhereye ku buryo bukoreshwa, Tα1 ikorana na Toll-imeze nk'iyakirwa kugira ngo ikore inzira nyinshi zerekana inzira zerekana inzira, bityo bigenga imikorere y'uturemangingo tw’umubiri hamwe n’imiyoboro ya cytokine, kandi bigere ku kugenzura neza imikorere y’umubiri y’umubiri.
Ku bijyanye n'ingaruka zongera ubudahangarwa bw'umubiri, Tα1 igira uruhare runini mu kwandura virusi, ibikorwa bya antitumor, kugenzura imiterere y’umubiri, hamwe n’ingaruka zo kurwanya indwara. Mu murima wa virusi, Tα1 yerekana amahirwe menshi yo gukoreshwa, haba ku ndwara zandura virusi nka hepatite B na C, cyangwa ku ndwara zandura virusi nka COVID-19. Uruhare rwa Tα1 mu ndwara zo kubura ubudahangarwa n'indwara ziterwa no gutwika byerekana ko bishobora gufasha kugarura ubudahangarwa bw'umubiri no kugabanya ibyangiritse. Muri rusange, Tα1 igira uruhare runini nko kongera ubudahangarwa bw'umubiri.
Inkomoko
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[6] Li CL, Zhang T, Saibara T, n'abandi. Thymosine alpha1 yihutisha kugarura T selile-yunganirwa itabuza antibody igisubizo mubakira badafite ubudahangarwa [J]. Immunopharmacology mpuzamahanga, 2002,2 (1): 39-46.DOI: 10.1016 / s1567-5769 (01) 00136-9.
Ibicuruzwa biboneka mubushakashatsi bukoreshwa gusa:
