Methylene blue da hanta mai kitse: abin da binciken gwaji ya gano

Hanta mai kitse suna ne guda da ake amfani da shi ga matsaloli daban-daban. Ga wani, abin da ke jawo ta shi ne yawan shan barasa na dogon lokaci. Ga wani kuma, shi ne samun sinadaran abinci fiye da buƙata tare da ƙarancin amsawa ga insulin da ƙarin kitse da ke isa hanta. Madubin ƙara girma na iya nuna taruwar kitse kawai a duka yanayin biyu, amma tushen abubuwan da ke jawo su ya bambanta. Wannan bambanci ne ke ƙayyade abin da kowane gwaji zai iya tabbatarwa.

Binciken da aka wallafa kan methylene blue da hanta mai kitse kaɗan ne, kuma dukkan binciken wannan batu an yi shi ne kafin matakin gwaji a mutane. Bincike uku kan beraye da ƙananan beraye ne aka fi ambata, kuma ba dukkansu suke nuna abu ɗaya ba. Wani binciken ciyarwa da ethanol ya gyara sauyin redox amma bai canza kitsen hanta ba. Wani binciken abinci mai yawan kitse ya rage kitsen hanta tare da sauyin sigina. Wani binciken dabbobi masu lafiya ya gano sakamakon peroxidation na lipid da ya saɓa tsakanin hanta da ƙoda. Idan aka karanta su tare, suna nuna dalilin da ya sa dole a bambanta ma'aunan sakamako guda uku: sauyin redox, kunna sigina, da taruwar kitse a nama.

Ma'aunan sakamako guda uku da sauƙin gaurayawa

Ma'aunin redox yana bayyana yadda ake sarrafa electron. Rabon NAD+ da NADH a hanta yana nuna ko yanayin cikin sel ya fi karkata ga oxidation ko reduction. Oxidation na ethanol yana sauya NAD+ zuwa NADH, don haka shan barasa na dogon lokaci yana rage wannan rabo. Wani sinadarin rini da ke karɓar electron na iya sake ɗaga shi. Wannan aikin sinadarai ne, ba hujjar cewa kitsen da aka tara ya ragu ba.

Ma'aunin sigina yana bayyana tsarin sarrafawa. SIRT1 enzyme ne mai sarrafawa wanda ya dogara da NAD+ kuma yake sauya furotin da ke da hannu a aikin mitochondria da sarrafa lipid. AMPK yana aiki a matsayin mai gane ƙarancin makamashi; idan an kunna shi, yana ƙarfafa oxidation na sinadaran da ke samar da makamashi kuma yana takaita ƙera lipid. Idan wata takardar bincike ta bayyana cewa methylene blue ya kunna SIRT1 a hanta, tana bayyana sauyin sarrafawa ne. Har yanzu ba ta bayyana sakamako a majiyyaci ba.

Ma'aunin nazarin nama da madubin ƙara girma ko na sinadaran halittu yana bayyana hantar kanta. Misalan da aka saba amfani da su sun haɗa da adadin triglyceride a kowace gram ta nama, rinin Oil Red O don nuna kitse mai tsaka-tsaki, tantance kumburin sel da lahani ta hematoxylin da eosin, da aikin ALT a plasma. Wannan rukuni na uku kaɗai ne ke amsa ko methylene blue ya inganta taruwar kitse a hanta a wannan gwajin.

Bambanta waɗannan rukunai yana hana kuskuren fassara da aka fi yi: kyakkyawan sakamakon redox ko sigina ba yana nufin raguwar kitse a hanta ba ne.

Samfurin ethanol: an gyara redox, kitse bai canza ba

Mafi bayyananniyar shaida ta rashin raguwar kitse ta fito daga wani binciken ciyarwa da ethanol na dogon lokaci a berayen Wistar maza. Dabbobin sun samu ethanol a matsayin wani ɓangare na abinci na ruwa, wanda ya ƙaru har ya kai 36 bisa ɗari na jimillar makamashi. Rukunin kwatanci ya samu abinci da aka daidaita adadinsa da na rukunin ethanol, tare da glucose a maimakon makamashin ethanol. Rukuni ɗaya da ke samun ethanol da rukuni ɗaya na kwatanci sun kuma samu methylene blue a 130 mg a kowace liter ta abinci, kusan 42 mg a kowace kg a kowace rana, daga rana ta 5 zuwa rana ta 30.

An ƙiyasta yanayin redox ta amfani da sanannun nau'i-nau'i na sinadaran metabolism: lactate da pyruvate don cytosol, da 3-hydroxybutyrate da acetoacetate don mitochondria. A farkon ciyarwa da ethanol mai yawa, rukunin ethanol sun nuna manyan sauye-sauye: rabon NAD+ da NADH a cytosol ya ragu da kusan 62 bisa ɗari, na mitochondria kuma da kusan 71 bisa ɗari, tare da ƙarin glycerol 3-phosphate. Methylene blue ya juya yawancin waɗannan sauye-sauye kuma ya mayar da glycerol 3-phosphate kusa da ƙimar rukunin kwatanci, ba tare da canza adadin ethanol da aka sha, ƙaruwar nauyin jiki, ko ethanol a serum ba.

Kitsen hanta ya nuna wani sakamako daban. A rana ta 12, kafin babban taruwar kitse, triglyceride bai bambanta tsakanin rukunai ba. A rana ta 27, rukunin ethanol sun samu babban ƙaruwa a triglyceride ko sun samu methylene blue ko ba su samu ba. A rana ta 30, jimillar lipid ta ƙaru da kusan 89 bisa ɗari, triglyceride kuma da kusan 196 bisa ɗari a dabbobin da aka ciyar da ethanol; a nan ma rinin bai sauya sakamakon ba. Taruwar kitse a yankin tsakiyar ƙananan sassan hanta ta yi kama iri ɗaya, ko an yi maganin gwajin ko ba a yi ba. Marubutan sun kammala da cewa sauyin redox da ethanol ya jawo ba shi ne babban dalilin hanta mai kitse bayan ciyarwa na dogon lokaci a wannan samfurin ba. Fahimtar yadda sakamakon dabbobi da sel yake da alaƙa da haɗari ga mutane yana taimakawa a nan: wata hanyar aiki na iya zama ta gaske amma duk da haka ba ita ce ke sarrafa sakamakon ba.

Wannan shi ne binciken da za a ambata idan wani ya yi iƙirarin cewa duk wani gyaran redox dole ne ya kawar da kitsen hanta. A wannan tsarin gwajin, bai yi haka ba.

Samfurin matsalar metabolism: sigina tare da ƙarancin kitse, a ƙananan beraye

Wani sakamako daban ya fito daga binciken sel na hanta da ƙananan berayen da aka ciyar da abinci mai yawan kitse wanda ya mayar da hankali kan SIRT1 da AMPK. A sel na HepG2, sel na AML-12, da sel na hanta da aka ɗauko kai tsaye daga beraye, methylene blue ya ɗaga rabon NAD+ da NADH, ya ƙara furotin na SIRT1, ya rage acetylation na sinadarin sarrafawa PGC-1alpha, ya ƙara adadin DNA na mitochondria da amfani da oxygen, kuma ya kunna AMPK tare da ƙarin CPT-1 da PPARalpha da ya biyo baya. Lokacin da aka rage samar da SIRT1, kunna AMPK ya daina faruwa, wanda ya danganta wannan jerin matakai da SIRT1 a wannan tsarin sel. Rinin ya kuma yi adawa da siginar ƙera kitse daga sinadarin kunna LXR, wato T0901317, da kuma daga fallasa sel ga palmitate, ciki har da ƙarin samar da SREBP-1c, FAS, da ACC.

Sashen dabbobi ya yi amfani da ƙananan berayen C57BL/6 maza da aka ciyar da abinci mai kitse 60 bisa ɗari na tsawon makonni 8. An ba su methylene blue ta baki sau huɗu a mako a cikin makonni 4 na ƙarshe, a 3 ko 10 mg a kowace kg a kowace rana. Ƙananan berayen da suka samu maganin gwajin sun nuna ƙarancin rinin Oil Red O, ƙarancin triglyceride a hanta, ƙarancin kumburin sel da lalacewa mai alaƙa da kitse a nazarin nama, da ƙarancin ALT a plasma idan aka kwatanta da waɗanda aka ciyar da abinci mai yawan kitse amma ba su samu maganin gwajin ba. Binciken yadda sinadarin ke shiga da motsawa cikin jiki a wannan takarda ya gano cewa kusan 31 zuwa 35 bisa ɗari ne ke samuwa ga jiki bayan bayarwa ta baki. Hanji ya sha kusan duka sinadarin, amma metabolism ya sarrafa babban ɓangarensa. An kuma samu mafi girman rabon sinadarin a nama idan aka kwatanta da plasma a hanta, abin da aƙalla ya sa tasiri a hanta ya zama mai yiwuwa ta fuskar yadda sinadarin ke rarrabuwa a jiki.

Wannan shaida ce ta gaske ta raguwar taruwar kitse, amma iyakokinta ƙuntatattu ne. Gwaji ne na ɗan gajeren lokaci a ƙananan beraye, da dabbobi 9 zuwa 10 a kowane rukuni, abinci iri ɗaya, adadin sinadari biyu, da makonni huɗu na bayar da maganin gwaji. Yana gwada taruwar kitse da ke da alaƙa da metabolism da alamomin kumburin hanta mai kitse, ba cutar da ke da alaƙa da barasa ba. Kuma ba ya gwada cirrhosis, juyar da tabon nama, ko wani sakamako a mutane. Matsayin ma'aunan mitochondria da redox wajen fassara irin waɗannan sakamakon shi ne nuna cewa suna goyon bayan hasashen bincike, ba wai suna nuna adadin magani ko tsarin amfani ba.

Hoton yanayin nama mai lafiya: adadi ɗaya, sakamako masu saɓani a gaɓoɓi

Ana yawan haɗa bincike na uku cikin iƙirarin da suka shafi hanta, alhali bai dace a yi haka ba. A wani gwajin kwanaki 30 a berayen Wistar mata masu lafiya, dabbobi biyar sun samu methylene blue 1 mM a ruwan sha, wasu biyar kuma sun zama rukunin kwatanci. Superoxide dismutase, catalase, da glutathione a yanayin reduction ba su canza a hanta ko ƙoda ba. Peroxidation na lipid ya ɗan ƙaru a hanta kuma ya ragu a ƙoda. ALT da creatinine a serum sun ragu, ba tare da sauyi a nitrogen na urea a jini ba.

Fassara ta gaskiya ita ce cewa tasirin ya bambanta da nau'in nama a dabbobi masu lafiya, ba wai an magance wata cuta ba. Wannan fallasa ɗaya ta nuna ɗan ƙarfafa oxidation bisa wani ma'auni a hanta, da ɗan kariya bisa wannan ma'aunin a ƙoda, yayin da hanyoyin kariya na yau da kullum daga oxidation suka kasance ba tare da canji ba. Da dabbobi biyar a kowane rukuni kuma ba tare da samfurin cuta ba, wannan takarda tana gargaɗi game da kiran methylene blue sinadarin kariya daga oxidation na hanta gaba ɗaya. Tana kuma nuna dalilin da ya sa sauye-sauyen enzymes na hanta ke buƙatar a san takamaiman yanayin cutar kafin a ɗauke su a matsayin ingantawa.

Kwatanta gwaje-gwajen hanta guda uku

Teburin yana bayyana babban batu. Rini shuɗi mai kama, amma tsarin halitta daban-daban. Binciken ethanol yana bambanta nasarar redox da rashin nasarar rage kitse. Binciken abinci yana haɗa sigina da ingantawar kitse a samfurin gwaji ɗaya. Binciken dabbobi masu lafiya yana nuna cewa alamomin redox na iya sauyawa ta hanyoyi masu saɓani bisa ga gaɓar jiki.

Dalilin da ya sa ba za a yi iƙirarin magani daga wannan ba

Babu ɗaya daga cikin waɗannan binciken da ya haɗa mutane masu hanta mai kitse. Adadin sinadari, hanyoyin bayarwa, da tsawon lokaci sun bambanta tsakanin takardun binciken, kuma ba za a mayar da su tsarin amfani ga mutane ta hanyar sauƙaƙƙen lissafin daidaita girman jiki ba. Ƙananan rukunin dabbobi, musamman dabbobi uku a kowane lokacin auna redox a binciken ethanol da biyar a kowane rukuni a binciken dabbobi masu lafiya, suna barin rashin tabbas mai yawa. Jinsi, nau'in halitta, abubuwan da ke cikin abinci, da lokacin fara maganin gwaji dangane da lokacin lahani duk sun bambanta. Haka kuma, samfuran cuta guda biyu suna wakiltar tushen dalilai daban-daban, don haka kyakkyawan sakamakon abinci ba zai gyara sakamakon ethanol da bai nuna raguwar kitse ba, ko akasin haka ba.

Ga duk wanda aka tabbatar yana da cutar hanta, abin da ya fi gaggawa shi ne karanta bayanai game da taka tsantsan, ba game da magani ba. Bayanin gaba ɗaya na matakan taka tsantsan ga ƙoda da hanta game da methylene blue yana bayyana dalilin da ya sa raunin aikin gaɓa yake sauya tambayoyin aminci ko da takardar binciken dabbobi ta nuna sakamako mai kyau. Kai bayanin cutar da aka gano, sakamakon gwaje-gwajen baya-bayan nan, takamaiman samfurin da hanyar amfani da shi, da cikakken jerin magunguna zuwa ga ƙwararren likita. Tambayi wace shaida ce ke goyon bayan amfani da wannan samfurin don wannan manufa ga wanda yake da wannan matakin raunin aikin gaɓa.

A taƙaice: methylene blue ya sauya yanayin redox na hanta a samfurin ethanol ɗaya ba tare da rage kitsen da aka tara ba, ya kunna SIRT1 da AMPK tare da rage kitse a samfurin matsalar metabolism ɗaya na ƙananan beraye, kuma ya nuna tasirin redox da ya bambanta bisa ga gaɓa a beraye masu lafiya. Waɗannan alamu ne da za su jagoranci ƙarin bincike, ba ingantaccen maganin hanta mai kitse da aka tabbatar ba.