By Cocer Peptides 
kwanaki 25 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da kowane yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Bayani na AOD9604
AOD9604 shine peptide wanda aka samo daga guntun C-terminal na hormone girma na mutum (hGH). Ya ƙunshi amino acid 177-191 na hGH, tare da ƙarin ragowar tyrosine (Tyr) da aka ƙara a ƙarshen N-terminal na peptide, watau, Tyr-hGH 177-191. Jerin amino acid na AOD9604 yana ƙayyade daidaitattun sararin samaniya, wanda hakan ke rinjayar mu'amalarsa da masu karɓa da ƙwayoyin cuta daban-daban a cikin jiki. Ragowar tyrosine da aka ƙara a N-terminus na iya shafar kwanciyar hankali na peptide a cikin jiki, haɓakar ɗaukar kwayar halitta, da haɗin kai tare da takamaiman masu karɓa. AOD9604 na cikin nau'in mahadi na peptide, wanda ke shiga cikin tsarin tsarin ilimin lissafi daban-daban a cikin jiki, kamar siginar siginar da tsarin rayuwa. Saboda ƙayyadadden asali da tsarin sa, AOD9604 yana da ayyuka na musamman na ilimin lissafi, musamman yana nuna tasiri mai mahimmanci a cikin ƙa'idodin metabolism na lipid.
Hanyar AOD9604 a cikin Gudanar da Metabolism na Lipid
(1) Haɗin kai tare da hanyar β-adrenergic
Tsarin maganganun β-adrenergic mai karɓa: AOD9604 na iya rinjayar metabolism na lipid ta hanyar hulɗa tare da hanyar β-adrenergic, musamman ta hanyar tsarin β (3) -adrenergic receptor (β (3) -AR). A cikin ƙirar linzamin kwamfuta mai kiba, bayan kwanaki 14 a jere na allurar intraperitoneal na AOD9604, matakin magana na β (3) -AR RNA a cikin adipocytes ya karu. β (3) -AR shine mai karɓar lipolytic na farko a cikin adipocytes, kuma ƙara yawan maganganunsa yana inganta lipolysis. AOD9604 na iya haɓaka maganganun β (3) -AR ta hanyar kunna hanyoyin siginar da ke da alaƙa, don haka ƙara bayyanar da yanayinta a cikin sel. Yana iya yin tasiri akan ɗaurin wasu abubuwan rubutu zuwa yankin mai talla na β(3) -AR gene, don haka haɓaka haɓakar ƙaddamar da rubutun kwayoyin halitta.
Halayen cascading na kunna hanyar β-adrenergic: Lokacin da β(3) -AR magana ta ƙaru, yana ɗaure ga ligands don kunna hanyoyin sigina na ƙasa. Kunna β (3) - AR ma'aurata tare da sunadaran G, wanda ke haifar da kunna adenylate cyclase, wanda hakan yana ƙara matakan intracellular na manzo na biyu cyclic adenosine monophosphate (cAMP). cAMP yana kunna furotin kinase A (PKA), wanda ke kunna phosphorylates kuma yana kunna lipase na hormone-sensitive (HSL), babban enzyme a cikin lipolysis wanda ke haifar da hydrolysis na triglycerides a cikin fatty acids da glycerol, don haka inganta lipolysis da daidaita metabolism na lipid.
(2) Tasiri kai tsaye mai zaman kansa na β (3) -AR
Binciken gwaji mai tsanani: A cikin gwaje-gwaje masu tsanani tare da β (3) -AR gene-knockout mice, AOD9604 har yanzu yana ƙara yawan kashe kuzari da kuma iskar oxygen. Wannan yana nuna cewa tasirin tsarin AOD9604 akan metabolism na lipid bai dogara gaba ɗaya akan β (3) -AR ba. Ko da yake har yanzu ba a fahimce takamaiman hanyar ba, za a iya kasancewa madadin hanyoyin ko makasudin aiki kai tsaye. AOD9604 na iya yin aiki kai tsaye akan mitochondria, yana tasiri aikin mitochondrial da haɓaka β-oxidation na fatty acids. Mitochondria sune tsakiyar cibiyar makamashin salula, kuma fatty acid β-oxidation yana faruwa a cikin mitochondria. AOD9604 na iya haɓaka shigar da fatty acid zuwa cikin mitochondria da sauƙaƙe lalatawar iskar oxygen ta hanyar daidaita ayyukan sunadaran sufuri ko enzymes masu alaƙa akan membrane na mitochondrial, don haka ƙara kashe kuzari da iskar oxygen mai fatty acid.
Ƙarin ƙarin hanyoyin sigina: AOD9604 kuma yana da hannu wajen daidaita sauran hanyoyin sigina. Zai iya rinjayar aikin dangin mai karɓar mai karɓa (PPAR) na peroxisome proliferator. PPARs rukuni ne na masu karɓar makaman nukiliya waɗanda ke taka muhimmiyar rawa ta tsari a cikin metabolism na lipid, ma'aunin makamashi, da martanin kumburi. AOD9604 na iya yin hulɗa tare da PPARs don daidaita maganganun kwayoyin halittar da suka yi niyya, ta yadda za su shafi rubutun da fassarar kwayoyin halittar da ke da alaƙa da lipid metabolism, ta haka ne ke daidaita metabolism na lipid. Hakanan yana iya shiga cikin tsarin tsarin siginar insulin. Ko da yake AOD9604 ba shi da illa masu haifar da ciwon sukari da ke da alaƙa da hGH, yana iya yin tasiri a kaikaice ta hanyar daidaita tsarin siginar insulin.
Tasirin AOD9604
(1) Tasirin Nauyin Jiki da Kiba
Shaidar gwaji na dabba: A cikin ƙirar linzamin kwamfuta mai kiba, allurar intraperitoneal na AOD9604 na dogon lokaci (kwanakin 14 na gudanarwa na yau da kullun) ya rage girman nauyin jiki da kitsen jiki. Wannan raguwa a cikin nauyin jiki da mai yana da alaƙa da haɓakar β (3) -AR RNA matakan magana, yana nuna cewa AOD9604 yana inganta lipolysis ta hanyar daidaita maganganun β (3) - AR, don haka samun raguwa a cikin nauyin jiki da kitsen jiki. Musamman, an sami raguwar nauyin kitse na subcutaneous da visceral mai nauyi, tare da asarar nauyi gabaɗaya. A lokacin gwajin, ma'auni na yau da kullun na nauyin linzamin kwamfuta da daidaitattun ma'auni na bayan-mutuwar kitse na kitse sun nuna cewa berayen da aka yi wa magani na AOD9604 sun nuna raguwar nauyin jiki da kitse sosai idan aka kwatanta da ƙungiyar kulawa, tare da wannan raguwa yana nuna yanayin dogaro da kashi.
Hoto na 2 Yanzu da Manufofin Magunguna na gaba a cikin Gudanar da Nauyi
Don kula da kiba na ɗan adam, tasirin AOD9604 yana riƙe yuwuwar ƙimar aikace-aikacen. Kiba abu ne mai mahimmancin haɗari ga yawancin cututtuka na yau da kullum kamar cututtukan zuciya da ciwon sukari, kuma rage nauyin jiki da mai yana da mahimmanci don inganta yanayin lafiyar marasa lafiya.
(2) Tasiri kan Metabolism na Makamashi
Ƙara yawan Kudaden Makamashi: AOD9604 yana ƙara yawan kashe kuzari a cikin mice na al'ada da β (3) -AR gene knockout mice. A cikin berayen al'ada, an yi amfani da calorimetry kai tsaye don auna yawan iskar oxygen da samar da carbon dioxide, yana nuna cewa AOD9604 yana haɓaka ƙimar kuzarin kuzari sosai. Ana danganta wannan tasirin ga AOD9604 mai haɓaka lipolysis, tare da fatty acid da aka saki suna aiki azaman makamashin makamashi don iskar oxygen da amfani, don haka ƙara kashe kuzarin kuzari. A cikin β (3) -AR ƙwanƙwasa mice, kodayake tsarin aikinta bai dogara da β (3) -AR ba, ana lura da haɓakar kashe kuzarin kuzari, yana ƙara nuna cewa AOD9604 yana da hanyar ka'idar metabolism makamashi mai zaman kanta ta β (3) -AR.
Ka'idojin hadawan abu da iskar shaka: AOD9604 yana haɓaka tsarin iskar shaka mai mai. A cikin gwaje-gwajen salula, ta yin amfani da acid fatty acid mai raɗaɗi don bin diddigin metabolism na oxidative, an gano cewa ƙimar fatty acid oxidation an haɓaka cikin sel waɗanda aka yi da AOD9604. Wannan ba wai kawai yana taimakawa rage ajiyar kitse ba amma har ma yana ba da jiki da ƙarin kuzari. AOD9604 na iya haɓaka ingancin iskar oxygen da fatty acid ta hanyar daidaita aikin mitochondrial, haɓaka biogenesis na mitochondrial da aiki. Yana haɓaka magana da aiki na enzymes da ke da alaƙa da fatty acid oxidation a cikin mitochondria, gami da carnitine palmitoyltransferase I (CPT-I), wanda shine maɓalli mai iyakance ƙimar enzyme don fatty acid shiga mitochondria don iskar shaka. AOD9604 na iya haɓaka shigarwar fatty acid zuwa cikin mitochondria don bazuwar oxidative ta haɓaka maganganun CPT-I.
(3) Tasiri kan hanta lipid metabolism
Nazarin gwajin gwajin dabbobi na hanta: A cikin samfurin hanta mai kitse, an bincika tasirin AOD9604 akan metabolism na hanta. An raba mice zuwa ƙungiyar kulawa, ƙungiyar motsa jiki, motsa jiki + AOD9604 kungiyar, da kuma ƙungiyar kulawa ta AOD9604 kadai. Sakamakon ya nuna cewa matakan alanine aminotransferase (ALT) a cikin ƙungiyar AOD9604 kadai da kuma motsa jiki + AOD9604 sun kasance mafi ƙanƙanta fiye da waɗanda ke cikin ƙungiyar kulawa, yana nuna cewa AOD9604 yana da wani tasiri mai kariya akan lalacewar hanta. Ana iya dangana wannan ga AOD9604 yana daidaita metabolism na lipid a cikin hanta, yana rage yawan kitse a cikin hanta, ta haka yana rage steatosis na hanta da martani mai kumburi.
Tasiri akan enzymes hanta da cytokeratin-18 (CK18): Cytokeratin-18 alama ce ta biomarker da ke nuna apoptosis na hanta. A cikin gwajin, kodayake ƙungiyar monotherapy AOD9604 ba ta rage matakan CK18 sosai ba, kuma bai haifar da mummunan sakamako ba. Wannan yana nuna cewa AOD9604 na iya yin tasiri a kaikaice tsarin apoptosis na ƙwayoyin hanta ta hanyar daidaita metabolism na lipid na hanta, ta haka ne ke kare ƙwayoyin hanta daga lalacewa zuwa ɗan lokaci. AOD9604 na iya kula da ma'auni na hanta lipid metabolism ta hanyar daidaita maganganun kwayoyin halittar da ke da alaƙa da haɗin lipid, jigilar kaya, da lalacewa a cikin hanta, don haka rage yawan kitsen mai a cikin hanta.
Bayanan Bayani na AOD9604
(1) Aikace-aikace masu yuwuwa a cikin Maganin Kiba
Abũbuwan amfãni da Halaye: Idan aka kwatanta da magungunan asarar nauyi na gargajiya, AOD9604 yana da fa'idodi da yawa. Ba shi da illa masu alaƙa da ciwon sukari da ke hade da hGH. hGH na iya haifar da mummunan halayen kamar juriya na insulin da haɓaka matakan glucose na jini lokacin amfani da su don magance kiba. AOD9604 yana guje wa waɗannan illolin ta hanyar ƙirar tsarin sa na musamman. AOD9604 na iya daidaita tsarin metabolism na lipid musamman, inganta rushewar kitse, da haɓaka kashe kuzari, yana ba da kyakkyawan fata na jiyya ga marasa lafiya tare da kiba mai sauƙi. Tsarin aikinsa ya ƙunshi matakan da yawa, ba kawai ta hanyar daidaita hanyar β-adrenergic ba har ma ta hanyar wani tsari mai zaman kansa na β (3) -AR, yana ba da cikakkiyar hanyar shiga tsakani don maganin kiba.
(2) Aikace-aikace masu yuwuwa a cikin maganin cututtukan hanta
Mai yuwuwa don magance cututtukan hanta maras giya (NAFLD): NAFLD cuta ce ta hanta ta gama gari wacce ke da tarin kitse mai yawa a cikin hanta. A cikin samfurin linzamin kwamfuta na cututtukan hanta mai kitse, AOD9604 na iya daidaita metabolism na lipid na hanta, rage kitsen hanta, da haɓaka alamun aikin hanta. AOD9604 yana da takamaiman ƙimar aikace-aikacen don kula da NAFLD. Yana iya rage yawan kitse a cikin hanta ta hanyar haɓaka raguwa da jigilar mai a cikin hanta, ta haka yana rage ciwon hanta da martani mai kumburi. AOD9604 kuma na iya daidaita matsalolin oxidative da hanyoyin sigina masu kumburi a cikin hanta, ƙara kare ƙwayoyin hanta daga lalacewa.
Kammalawa
A matsayin peptide da aka samo daga yankin C-terminal na hormone girma na mutum, tsarin aikin AOD9604 a cikin daidaita tsarin metabolism na lipid ya haɗa da hulɗa tare da hanyar β-adrenergic da tasirin kai tsaye daga β (3) -AR. Ta hanyar waɗannan hanyoyin, AOD9604 yadda ya kamata yana rage nauyin jiki da kitsen jiki, yana ƙara yawan kashe kuzari, yana daidaita yawan iskar shaka, kuma yana inganta haɓakar hanta. Dangane da aikace-aikace, AOD9604 yana da babban alƙawari a cikin maganin kiba, maganin wasanni, da cutar hanta.
Sources
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[2] Cox HD, Smeal SJ, Hughes CM, et al. Ganewa da in vitro metabolism na AOD9604[J]. Gwajin Magunguna da Bincike, 2015,7 (1): 31-38.DOI: 10.1002/dta.1715.
[3] Stier H, Vos E, Kenley DL Tsaro da Haƙuri na Hexadecapeptide AOD9604 a cikin Mutane [J]. Jaridar Endocrinology da Metabolism, 2013,3:7-15.
https://api.semanticscholar.org/CorpusID:56559133
[4] Witkamp R F. Manufofin Magunguna na yanzu da na gaba a cikin Gudanar da Weight[J]. Binciken Magunguna, 2011,28 (8): 1792-1818.DOI: 10.1007 / s11095-010-0341-1.
Samfura akwai don amfani da bincike kawai:
