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ụbọchị 25 gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Oke ibu na nsogbu metabolic metụtara ya aghọwo ihe gbasara ahụike ọha na eze zuru ụwa ọnụ, na-eme ka ịchọọ enyemaka dị mma ma dị irè dị oke egwu. Ọ bụ ezie na homonụ na-eto mmadụ (hGH) na-egosi ikike ịgwọ oke ibu, nchegbu nchekwa na-egbochi iji ya ogologo oge. AOD9604, mpempe peptide sitere na mpaghara C-terminal nke hGH (Tyr-hGH177-191), achọpụtala na ọ nwere ọrụ na-ebelata abụba nke hGH na-enweghị mmetụta ọjọọ ya. Ọmụmụ ihe na-adịbeghị anya agbasawanyela na ọrụ ya, yana antioxidant na mmetụta nkwado metabolic na-apụta dị ka ebe nyocha isi.
Ọgụgụ 1 Oke oke ibu na ndị okenye US (afọ 20-74).
1. Mmetụta antioxidant nke AOD9604
Njikọ dị n'etiti nrụgide oxidative na ọrịa
Nchegbu oxidative na-ezo aka na ọnọdụ ebe, n'okpuru mkpali dị iche iche na-emerụ ahụ, ahụ na-emepụta oke ikuku oxygen na-emeghachi omume (ROS) na ụdị nitrogen reactive (RNS), na-eduga ná mmebi oxidative karịa ikike ahụ nwere ikpochapụ ụdị ndị a. Enweghị ahaghị nhata n'etiti sistemu oxidative na antioxidant na-ebute mmebi anụ ahụ. Ọtụtụ ọrịa, gụnyere ọrịa obi, ọrịa shuga, ọrịa neurodegenerative, na ọrịa imeju na-adịghị egbu egbu (NAFLD), jikọtara ya na nrụgide oxidative. Na steeti ọrịa ndị a, ọkwa ROS intracellular dị elu na-awakpo biomolecules dị ka lipids, proteins, na DNA, na-eduga na arụrụ ọrụ cellular na ọnwụ.
AOD9604 Antioxidant Mechanism of Action
AOD9604 na-arụ ọrụ ya site na ịhazi sistemu enzyme antioxidant intracellular. Superoxide dismutase (SOD), glutathione peroxidase (GPx), na catalase (CAT) bụ ihe dị mkpa enzymes antioxidant intracellular nke nwere ike imebi ROS ma nọgide na-enwe nguzozi redox intracellular. AOD9604 nwere ike meziwanye okwu ma ọ bụ ọrụ nke enzymes antioxidant ndị a, si otú a na-eme ka ikike nchekwa nchekwa sel dị elu. N'aka nke ọzọ, AOD9604 nwere ike isonye ozugbo na mkpochapụ nke radicals efu. Ụfọdụ otu dị n'ụdị molekụla ya nwere ike ịnwe ike ijide ROS na RNS, si otú ahụ belata mmebi ha na sel.
N'ime ọmụmụ ihe na-eji ụdị òké nke ọrịa imeju abụba na-adịghị egbu egbu, ọgwụgwọ na AOD9604 mere ka mbelata malondialdehyde (MDA) dị ukwuu na anụ ahụ imeju. MDA bụ ngwaahịa nke peroxidation lipid, yana mbelata ọkwa ya na-egosi mbelata nke nrụgide oxidative. Ọrụ SOD na GPx na imeju mụbara, na-atụ aro na AOD9604 nwere ike ibelata mmebi nrụgide oxidative site n'ịkwalite ọrụ nke enzymes antioxidant. Nke a na-egosi na AOD9604 nwere mmetụta dị mma n'ịkwalite ọnọdụ nrụgide oxidative nke imeju, na-enye ihe akaebe nnwale maka ngwa ya na ọgwụgwọ ọrịa ndị metụtara ya.
2. Mmetụta Nkwado Metabolic nke AOD9604
Mmetụta na Lipid Metabolism
AOD9604 na-egosipụta mmetụta nchịkwa dị mkpa na metabolism lipid. N'ụdị òké buru ibu, ịgba ọgwụ intraperitoneal ogologo oge nke AOD9604 butere mbelata ibu ahụ na abụba anụ ahụ. Mmetụta a nwere ike jikọta ya na ụzọ β-adrenergic, karịsịa β (3) -adrenergic receptor (β (3) -AR), onye na-anabata lipolytic bụ isi na adipocytes. Mgbe ụbọchị 14 nke nchịkwa AOD9604 na oke oke ibu, ọkwa ọkwa nke β (3) -AR RNA mụbara, na-eweghachi ọkwa β (3) AR RNA na oke oke oke na ọkwa yiri nke ụmụ oke na-adabere na ya, si otú ahụ na-akwalite lipolysis na ịkwalite mmetụta lipolytic. Na β (3) - AR knockout ụmụ oke, iji ogologo oge nke AOD9604 emeghị ka mgbanwe mgbanwe dị arọ na mmetụta lipolysis dị ka ụmụ oke nchịkwa anụ ọhịa, na-egosi na β (3) -AR na-arụ ọrụ dị mkpa na nhazi nke AOD9604 nke metabolism lipid. N'ime nnwale siri ike, AOD9604 ka na-abawanye mmefu ike yana oxidation abụba na ụmụ oke β (3) -AR gene knockout ụmụ oke, na-atụ aro na AOD9604 nwekwara ike imetụta metabolism lipid site na ụzọ ndị ọzọ.
Ọnụ ọgụgụ 2 Mmetụta nke otu intraperitoneal (ip) kwa ụbọchị nke saline, AOD9604, ma ọ bụ hormone na-eto eto (hGH) na ịdị arọ ahụ na-agbanwe na nwoke C57BL / 6J (A) ma ọ bụ oke (ob / ob) ụmụ oke (B) karịa ụbọchị 14.
Mmetụta na carbohydrate metabolism
N'ihe gbasara carbohydrate metabolism, AOD9604 dị iche na hGH. Nnwale ụlọ ọgwụ na-egosi na AOD9604 enweghị mmetụta na ọkwa IGF-1 serum, na-akwado echiche na ọ naghị eme site na IGF-1. Nsonaazụ sitere na nnwale nnabata glucose ọnụ gosiri na, n'adịghị ka hGH, AOD9604 anaghị emetụta metabolism carbohydrate na-adịghị mma. Nke a pụtara na AOD9604 nwere ike ịhazi metabolism lipid na-enweghị itinye aka na metabolism carbohydrate nkịtị, na-enye uru pụrụ iche n'ịkwalite ọkwa metabolic.
Mmetụta na imeju metabolism
N'ime ọmụmụ banyere ụmụ oke nwere ọrịa imeju na-adịghị egbu egbu, AOD9604 ọ bụghị naanị na-emetụta metabolism lipid kamakwa na-achịkwa ọnọdụ metabolic zuru oke nke imeju. Na mgbakwunye na ibelata nrụgide oxidative, AOD9604 nwere ike melite steatosis imeju site na ịhazi okwu nke mkpụrụ ndụ ihe nketa metụtara njikọ lipid, njem, na metabolism na imeju. Ọ nwere ike imetụta ngosipụta nke enzymes isi dị ka fatty acid synthase (FAS) na acetyl-CoA carboxylase (ACC), na-ebelata njikọ abụba abụba n'ime imeju, na-akwalite fatty acid β-oxidation, ma si otú a na-ebelata mkpokọta abụba imeju.
3. Ngwa nwere ike nke AOD9604's Dual Action
Ngwa dị na oke ibu na Ọrịa Metabolic emetụtara
Nyere AOD9604's antioxidant and metabolic support effects, ọ na-ejide uru ngwa na ọgwụgwọ oke ibu na ọrịa metabolic metụtara ya dị ka ụdị ọrịa shuga 2 na ọrịa imeju na-adịghị egbu egbu. Maka ndị ọrịa buru oke ibu, AOD9604 nwere ike ịkwalite metabolism lipid, belata abụba anụ ahụ, ma melite mmetụta insulin, si otú a na-enyere aka ịchịkwa glucose ọbara. Maka ndị ọrịa na-arịa ọrịa imeju na-adịghị egbu egbu, ọ nwere ike belata mmebi imeju oxidative ma mezie metabolism lipid imeju, nke nwere ike na-eje ozi dị ka atụmatụ ọhụrụ iji melite ọrụ imeju na ngwa ngwa ọrịa.
Ngwa na Egwuregwu Nutrition
N'ihe gbasara nri egwuregwu, AOD9604's antioxidant and metabolic support properties na-adọrọkwa mma. N'oge ọzụzụ dị elu, ndị na-eme egwuregwu na-emepụta ROS buru ibu, na-eduga ná mmebi nrụgide oxidative, ebe ike metabolism na-achọ ịbawanye ụba. AOD9604 nwere ike inye aka kpochapụ ROS, belata ike ọgwụgwụ na mmebi ahụ, ebe ọ na-akwalite oxidation abụba maka ume, si otú ahụ na-eme ka ntachi obi na-agbake na ike mgbake. Ọ bụ ezie na AOD9604 na-egosipụta ezigbo antioxidant na mmetụta nkwado metabolic, nchekwa ya dị oke mkpa. Ọtụtụ ọmụmụ enyochala nchekwa nke AOD9604. Na isii randomized, abụọ-ìsì, placebo-controlled tests, AOD9604 enweghị mmetụta na serum IGF-1 ọkwa, ọ dịghị mmetụta ọjọọ na carbohydrate metabolism, na ọ dịghị anti-AOD9604 mgbochi achọpụtara. Enweghị mgbaama mwepu ma ọ bụ ihe omume ọjọọ metụtara nri AOD9604 ka akọọrọ. N'ime ọmụmụ toxicology na-adịghị ala ala na oke na anụ cynomolgus, nchịkwa ọnụ ogologo oge nke AOD9604 gosipụtara nchekwa ya n'ozuzu ya, na-enweghị ihe ịrịba ama nke genotoxicity.
Ọgụgụ 3 In vitro mmebi nke AOD9604 na plasma oke na okpomọkụ ụlọ. Mgbe nkeji 56 gachara, a na-ewepụ peptide kpamkpam. Ọkara ndụ dị ihe dịka nkeji 4. Mpụta nke AOD9604 amino-terminal truncated iberibe (-xaa) ka egosiri.
4. Nkwubi okwu
AOD9604, dị ka iberibe peptide nwere omume abụọ pụrụ iche, na-enyere aka na antioxidant na nkwado metabolic. Ọrụ antioxidant ya na-enyere aka ibelata mmebi anụ ahụ metụtara nrụgide oxidative, ebe ọrụ nkwado metabolic ya na-achịkwa nke ọma lipid, carbohydrate na metabolism imeju. Nke a na-eme ka ọ dị ịrịba ama na ọgwụgwọ oke ibu na ọrịa metabolic metụtara ya, yana nri nri egwuregwu.
Isi mmalite
[1] Dehbashi M, Fathie M, Hosseini SRA, et al. اثر هشت هفته تمرین استقامتی و تزریق قطعه لیپولیتیک هورمون رشد (AOD9604) بر آنزیمهای کبد و CK18 مشاهور. Ụlọ akwụkwọ sekọndrị, 2021[C]. https://api.semanticscholar.org/CorpusID:236556287
[2] EMIM, Kenley DL Safety and Metabolism nke AOD9604, Ihe Nri Nri Maka Ahụ Ike Metabolic [J]. Akwụkwọ akụkọ nke Endocrinology na Metabolism, 2014,4:64-77. https://api.semanticscholar.org/CorpusID:67761634
[3] Stier H, Vos E, Kenley DL Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans[J]. Akwụkwọ akụkọ nke Endocrinology na Metabolism, 2013,3:7-15. https://api.semanticscholar.org/CorpusID:56559133
[4] Melnikova I, Ụgwọ ọrụ D. Ọgwụ mgbochi oke ibu [J]. Nature Nyochaa Nchọpụta ọgwụ ọjọọ, 2006,5 (5):369-370.DOI:10.1038/nrd2037.
[5] Heffernan M, Summers RJ, Thorburn A, et al. Mmetụta nke GH mmadụ na iberibe lipolytic ya (AOD9604) na metabolism lipid na-eso ọgwụgwọ na-adịghị ala ala na oke oke na beta (3) - AR kụrụ aka. Endocrinology, 2001,142 (12):5182-5189.DOI:10.1210/endo.142.12.8522.
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