▎ ʻImi Dermorphin
He aha ke kumu noiʻi o Dermorphin?
Ka ʻimi ʻana i nā mea bioactive: Mai ka 1970s, ua hoʻolaʻa ʻia nā ʻepekema i ka ʻimi ʻana i nā mea me nā hana physiological kūikawā mai nā mea ola. Ua hoʻomaopopo mālie ka poʻe i ka wā lōʻihi o ka hoʻomohala ʻana, e hana nā holoholona i nā biomolecules kūʻokoʻa e hoʻololi i ke kaiapuni a mālama i nā hana ola, a he mau waiwai lāʻau koʻikoʻi kēia mau molekala.
ʻO ka ʻokoʻa o ka ʻili Amphibian: He nui nā hana o ka ʻili o nā amphibians, e like me ka hanu, pale, a me ka huna. Hiki i nā ʻili ʻili o nā amphibians ke hūnā i ka nui o nā mea bioactive, kahi mea nui i ka pale ʻana i nā ʻenemi kūlohelohe a me ka hoʻololi ʻana i ke kaiapuni. Aia i loko o ka ʻili huna o nā amphibians nā mea waiwai peptide waiwai, nona nā ʻano hana like ʻole a me nā hana olaola like ʻole, e huki ana i ka manaʻo o nā ʻepekema he nui.
ʻO ka ʻike ʻana o Dermorphin: I ka makahiki 1981, ua hoʻokaʻawale mua nā kānaka ʻepekema ʻItalia iā Dermorphin mai nā ʻili huna o ka rana lāʻau ʻAmelika Hema (Phyllomedusa sauvagii). Ma o ka nānā ʻana i nā ʻāpana o ka ʻili huna o ka rana lāʻau a me ka ʻike ʻana i nā hana biological, ua ʻike ʻia ʻo Dermorphin i loko o ia mea he hopena analgesic potent a me kahi pilina kiʻekiʻe no nā mea hoʻokipa opioid. Ua wehe kēia ʻike i kahi kuhikuhi noiʻi hou ma ke kahua o ka mālama ʻana i ka ʻeha.
He aha ke ʻano o ka hana a Dermorphin?
1. Hoʻopaʻa i nā mea hoʻokipa Opioid
ʻO Dermorphin kahi peptide like-opioid ikaika e hiki ke hoʻopaʻa paʻa i nā μ-opioid receptors. Hoʻopili kēia hoʻopaʻa ʻana i nā mea loaʻa, ka hopena i ke ʻano o nā hopena physiological [1, 2] . Eia kekahi laʻana, i nā hoʻokolohua holoholona, ua hōʻike i ka hopena analgesic ikaika [1, 2] . Hiki ke hoʻokō ʻia kona hopena analgesic ma ke kāohi ʻana i ka lawe ʻana i nā hōʻailona ʻeha. Ke hoʻouna ʻia nā hōʻailona ʻeha i nā neurons, e hoʻoulu ʻia ka hauʻoli a me ke kī ʻana o nā neurons. Ma hope o ka hoʻopaʻa ʻana o Dermorphin i ka μ-opioid receptor, hiki iā ia ke kāohi i ka hauʻoli o nā neurons, a laila e hōʻemi i ka lawe ʻana i nā hōʻailona ʻeha.
2. Nā hopena ma ka Pūnaehana Nervous
Nā hopena ma ka pae kuamoʻo
Ma nā haʻawina kanaka, ua ʻike ʻia e hiki i ka infusion intravenous o dermorphin ke hoʻoulu i ka piʻi nui a hoʻomau i ka paepae nociceptive flexor reflex i nā mea manawaleʻa olakino [2] . Hōʻike kēia i hiki i ka dermorphin ke kāohi i ka lawe ʻana i nā hōʻailona nociceptive ma ka pae o ka spinal cord. ʻIke ʻia kēia hopena i nā kumuhana me ka ʻeha o ke kuamoʻo maʻi mau loa, e hōʻoia hou ana i ka hana nui o ka dermorphin i ka pale ʻana i ka hoʻoili nociceptive ma ka pae o ka spinal cord.
Hiki i ka Naloxone ke hoʻohuli i kahi hapa (ma kahi o 50%) i ka hopena inhibitory o dermorphin ma ka nociceptive spinal reflex. ʻO kēia paha ke ʻano o ka hui ʻana o dermorphin me nā heluna ʻokoʻa o nā mea hoʻokipa opioid spinal e hana i kahi hopena analgesic [2].
Nā hopena ma ka Pūnaehana Nervous Central
Hoʻopuka ka Intracerebroventricular administration o DM i kahi hana antinociceptive lōʻihi [1] . Hōʻike kēia i hiki i ka dermorphin ke hoʻokō i kahi hopena analgesic ma ka hana ʻana i ka ʻōnaehana nerve waena. Eia nō naʻe, ʻaʻole maopopo loa ka hana kikoʻī o ka dermorphin i loko o ke kikowaena kikowaena.
I ka rabbit hoʻokolohua, ma hope o intravenous injection of dermorphin, na rabbit 'ano i hōʻike i ka nui piʻi i loko o ka manawa o ka noho malie a me ka immobile, a me ka emi ana o nā hana manawaleʻa, akā, ia mea,ʻaʻohe hopena i ke kumu a me ka pinepine o ka hippocampal electroencephalogram [3] . Hōʻike kēia i ka hopena o ka dermorphin i kekahi mau ʻano kikoʻī a me nā wahi o ka ʻōnaehana nerve.
3. Nā hopena ma ka ʻōpū o ka ʻōpū
He hopena ko Dermorphin i ka hoʻoulu ʻana o ka ʻōpū i nā ʻiole. Hoʻohālikelike ʻia me ka morphine, ʻo ka intracerebroventricular injection o dermorphin ke kāohi i ka hoʻoulu ʻana o ka ʻōpū e like me ka morphine, a ʻo kāna hana he 143 mau manawa ma mua o ka morphine [4] . ʻOi aku ka maikaʻi o ka hopena antagonistic o ka naloxone ma dermorphin ma mua o ka morphine. Hiki i ka Intracerebroventricular administration o quaternized naloxone ke kū'ē i ka hopena o ka intracerebroventricular dermorphin ma ka ʻōpū, ʻoiai ʻo ka intraperitoneal injection wale nō ka hopena ma ka hopena o 8mg / kg. ʻAʻole pono loa ka Dermorphin i lawelawe ʻia intraperitoneally i ka nui o ka hopena (0.56 micrograms no ka ʻiole). ʻO ka hoʻonui ʻana i ka nui o ka intraperitoneal injection o dermorphin (mai 12 a 6400 micrograms i kilokani) he hopena pale i ka propulsion intestinal i kūʻokoʻa i ka dose, akā ʻaʻole ʻoi aku ma mua o 50%. ʻO kahi kiʻekiʻe kiʻekiʻe o ka naloxone (30mg/kg, intraperitoneal injection) hiki ke kūʻē i ka hopena o kēia intraperitoneal injection. Hōʻike kēia i ka hopena o ka dermorphin ma ka ʻōpū e pili ana i nā ʻāpana kikowaena a me nā peripheral.
4. Nā hopena ma nā ʻiʻo
Ua aʻo ʻia ka hana Dermorphin ma ka ʻāpana ʻāpana o ka ʻiʻo o ka ʻōpū o ka rana e kahi mea hoʻopaʻa mechanographic [5] . Hōʻike nā hopena noiʻi e hiki i ka dermorphin (10 (-5) -10 (-8) M) ke pale i ka hana o ka acetylcholine, ka hana manawaleʻa, a me ka hoʻohaʻahaʻa ʻana i ka ʻiʻo ma muli o ka hoʻoulu ʻana i ka uila. He paʻakikī kēia mau hopena a pau e hoʻohuli. Inā hoʻokomo ʻia ka dermorphin i loko o ka incubation medium i ka wā K (+) depolarization (KCl - 100mM) o ka ʻiʻo, ʻaʻole hiki iā ia ke pale i nā hana kuʻuna a hoʻoulu ʻia. No laila, loaʻa i ka dermorphin kahi hopena e pili ana i ka volta a hiki ke hana ma luna o nā kahawai Ca (2+) e pili ana i ka volta o ka membrane cell muscle.
5. Ka pilina ma waena o ka Molecular Structure and Mechanism of Action
Ua hoʻokō ʻia nā hoʻohālikelike mechanical molecular ma dermorphin (Pattabiraman N, 1986). Hōʻike ka noiʻi i ka D-Ala2 ma ka N-terminus a me ka L-Pro6 koena ma ka C-terminus i ka dermorphin sequence e hōʻike ana i ka hiki ke hiki i kahi β-turn. Mai ka hiʻohiʻona stereochemical, ʻekolu paha ʻano (II', III', a me V') o nā β-huli ma ka N-terminus o ka peptide, a ʻelua ʻano (I a me III) o nā β-huli ma ka C-terminus. Ma ka helu mechanics molecular, eono conformations i pelu ʻia a me hoʻokahi conformation lōʻihi i manaʻo ʻia e loiloi i ke kūpaʻa pili o dermorphin. Ma waena o lākou, ʻekolu conformation i pelu ʻia he haʻahaʻa ka ikehu a loaʻa nā ʻano maʻamau penei: ikehu like, ʻekolu mau paʻa hydrogen, kahi ʻāpana β-sheet semi-rigid, a me kahi pilina Tyr1-Tyr5 maikaʻi. Hiki i ke ola o ka β-sheet structure ke hana i kahi hana i ka pilina koho ma waena o dermorphin a me ka μ-receptor.
He aha nā mea hoʻohana o Dermorphin?
Hoʻohanaʻia no ka hoʻoponoponoʻana i kaʻeha Postoperative: Ua hōʻikeʻia kahi haʻawina randomized, placebo-controlled ma 1985 i ka Dermorphin i lawelaweʻia ma ke ala intrathecal iʻoi aku ka maikaʻi ma mua o ka placebo a me ka morphine reference compound i ka mālamaʻana i kaʻeha postoperative [6, 7] . Hōʻike kēia i hiki ke loaʻa i ka Dermorphin ka mana nui i ka hoʻomaha ʻana i ka ʻeha postoperative. No nā poʻe maʻi postoperative, ʻaʻole hiki i ka hoʻoponopono ʻeha maikaʻi ke hoʻomaikaʻi wale i ka hōʻoluʻolu o nā maʻi akā kōkua pū kekahi i nā maʻi e hoʻōla a hoʻi i ke ola maʻamau.
Hoʻohana i ka Palliative Care: E noʻonoʻo ana i kāna hopena analgesic maikaʻi loa, ua manaʻo ʻia ʻo Dermorphin no ka hoʻohana ʻana i ka mālama palliative o nā maʻi maʻi holomua [6, 7] . Ma ka mālama palliative, hoʻomaha i ka ʻeha o nā maʻi he pahuhopu koʻikoʻi, a ʻo Dermorphin, me kāna hopena analgesic ikaika a me ka haʻahaʻa haʻahaʻa o nā hopena ʻaoʻao, hāʻawi i kahi koho hiki ke hoʻomaha i ka ʻeha o nā maʻi maʻi.
ʻO ka hopena Inhibitory on Spinal Pain: Ua hōʻike nā haʻawina e hiki iā Dermorphin ke kāohi i ka laweʻana o ka nociception i loko o ke kuamoʻo. I nā limahana olakino, hiki i ka infusion intravenous o 0.16mg / kg o Dermorphin ke hoʻonui nui a hoʻomau i ka paepae o ka nociceptive flexor reflex [8] . Uaʻike pūʻia nā hopena like i nā kumuhana me kaʻeha o ke kuamoʻo mau loa, e hōʻike ana i ka hana nui o Dermorphin i ka pae o ke kuamoʻo e kāohi i ka laweʻana i kaʻeha. Hāʻawi kēia hopena pale i ka ʻeha spinal i ka manaʻolana hou no ka mālama ʻana i nā maʻi e loaʻa ana i nā maʻi ʻeha pili i ke kuamoʻo.
I ka hopena, ʻo Dermorphin kahi peptide opioid-like potent e hiki ke hoʻopaʻa i nā mea hoʻokipa μ-opioid, e hōʻike ana i kahi hopena analgesic koʻikoʻi a ke kāohi nei i ka lawe ʻana i nā hōʻailona nociceptive i loko o ka spinal cord. Loaʻa iā ia nā noi i ka mālama ʻana i ka ʻeha postoperative, mālama palliative, etc., lawe mai i nā manaʻo hou no ka mālama ʻana i ka ʻeha.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He kanaka noiʻi ʻo Giuliano Fontani me ke Kulanui o Siena, Italia, e kālele ana i nā neurosciences a me ka physiology. Ua aʻo ʻo ia i nā hopena o ka dermorphin, kahi peptide kūlohelohe, ma ke ʻano a me ka hana uila hippocampal i nā rabbit, e hāʻawi ana i ka hoʻomaopopo ʻana i ka hana opioid receptor. ʻIke pū kāna hana i ka pilina ma waena o ka hana o ka lolo a me ka ʻano, me nā paʻi i loko o nā puke pai e like me Life Science. Ua helu ʻia ʻo Giuliano Fontani ma ka ʻōlelo kuhikuhi [3].
