{"id":4780,"date":"2024-08-04T15:26:43","date_gmt":"2024-08-04T15:26:43","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=4780"},"modified":"2024-08-04T15:26:43","modified_gmt":"2024-08-04T15:26:43","slug":"cyclopamine","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/tr\/siklopamin\/","title":{"rendered":"Meyan k\u00f6k\u00fc siklopamin ve kokulu orkidenin toplam flavonoidlerinin kombinasyon tedavisinin pulmoner fibrozis fareleri \u00fczerindeki etkisi"},"content":{"rendered":"

Meyan k\u00f6k\u00fc siklopamin ve kokulu orkidenin toplam flavonoidlerinin kombinasyon tedavisinin pulmoner fibrozis fareleri \u00fczerindeki etkisi
\nPulmoner fibrozis (PF), \u00e7e\u015fitli pulmoner kompartmanlarda ba\u011f dokusu b\u00fcy\u00fcmesinin e\u015flik etti\u011fi, \u00e7ok say\u0131da kronik solunum sistemi lezyonunu i\u00e7eren, belirgin histopatolojik paternleri olan kronik ilerleyici bir akci\u011fer hastal\u0131\u011f\u0131d\u0131r. Bunlar aras\u0131nda interstisyel akci\u011fer hastal\u0131\u011f\u0131 ve idiyopatik pulmoner fibrozis (IPF), pulmoner parankimal progresif fibrozisin en ciddi ve geri d\u00f6n\u00fc\u015f\u00fc olmayan hastal\u0131klar\u0131d\u0131r. PF anormal doku onar\u0131m\u0131ndan kaynaklan\u0131r ve s\u00fcrekli ciddi doku hasar\u0131 ve h\u00fccresel stres ile ili\u015fkilidir. Bu anormal \u00f6zellik, epitel h\u00fccre bariyerinin yetersiz onar\u0131m\u0131n\u0131 i\u00e7erir, buna fibroblastlar\u0131n bozulmu\u015f reg\u00fclasyonu e\u015flik eder, alveolar epitel h\u00fccrelerinde ve fibroblastlarda derin de\u011fi\u015fikliklere yol a\u00e7ar, fibrotik alveolar duvarlar\u0131n kal\u0131nla\u015fmas\u0131, bozulmu\u015f gaz iletimi, s\u0131n\u0131rl\u0131 ventilasyon paternleri ve nihayetinde solunum yetmezli\u011fi ile karakterize kontrols\u00fcz fibrozis ile sonu\u00e7lan\u0131r. Son y\u0131llarda, PF hastal\u0131\u011f\u0131 modern t\u0131p alan\u0131nda insan sa\u011fl\u0131\u011f\u0131n\u0131 ciddi \u015fekilde tehlikeye atm\u0131\u015ft\u0131r. Tan\u0131 y\u00f6ntemlerinin s\u00fcrekli ilerlemesi ve n\u00fcfusun ya\u015flanmas\u0131 nedeniyle, PF'nin mortalite ve insidans oran\u0131 artmaya devam etmektedir. Bu hastal\u0131\u011f\u0131n patogenezi karma\u015f\u0131kt\u0131r ve patolojik mekanizmas\u0131 hala belirsizdir. Hastalar\u0131n klinik belirtileri, akci\u011fer dokusu kompliyans\u0131nda ilerleyici d\u00fc\u015f\u00fc\u015f, dif\u00fczyon fonksiyonunda azalma ve ventilasyon\/kan ak\u0131\u015f\u0131 dengesizli\u011fidir; bu da hastalarda refrakter dispneye ve nihayetinde solunum yetmezli\u011fi ve \u00f6l\u00fcme yol a\u00e7ar.
\nHedgehog (Hh) yolu embriyonik geli\u015fim ve doku yeniden \u015fekillenmesinde \u00f6nemli bir rol oynar. Hh sinyal yolu temel olarak sinyal molek\u00fclleri (SHH, IHH, DHH), transmembran resept\u00f6rleri (Ptch, SMO) ve a\u015fa\u011f\u0131 ak\u0131\u015f transkripsiyon fakt\u00f6rlerinden (Gli1 protein ailesi) olu\u015fur. Aktivasyondan sonra, Hh yola\u011f\u0131 etkilerini esas olarak Gli1 protein ailesi arac\u0131l\u0131\u011f\u0131yla g\u00f6sterir. IPF'de Hh yolunun aktivitesinin artt\u0131\u011f\u0131 do\u011frulanm\u0131\u015f ve fibrozun yeniden \u015fekillendi\u011fi alandaki alveolar epitel ve submukozal fibroblastlarda SHH ve sinyal efekt\u00f6rlerinin \u00f6nemli \u00f6l\u00e7\u00fcde ekspresyonu tespit edilmi\u015ftir. Akci\u011ferlerde, SHH tedavisi fibroblast proliferasyonunu, sa\u011fkal\u0131m\u0131n\u0131, g\u00f6\u00e7\u00fcn\u00fc ve h\u00fccre d\u0131\u015f\u0131 matris (ECM) \u00fcretimini art\u0131rm\u0131\u015f, ancak \u03b1 - d\u00fcz kas aktin (\u03b1 - SMA) ekspresyonunu art\u0131rmam\u0131\u015ft\u0131r. Bleomisin ile ind\u00fcklenen PF modelinde, SHH ekspresyonu hava yolu ve alveolar epitel h\u00fccrelerinde y\u00fckselmi\u015ftir. Bleomisin modelinde, Hh sinyalini inhibe etmek fibrozu engellemez, ancak fibroz s\u0131ras\u0131nda SHH'nin a\u015f\u0131r\u0131 ekspresyonu PF'yi \u015fiddetlendirir. Bu nedenle, SHH sinyali normal akci\u011fer geli\u015fimi ve interstisyel homeostaz\u0131n s\u00fcrd\u00fcr\u00fclmesi i\u00e7in \u00e7ok \u00f6nemli olmas\u0131na ra\u011fmen, PF'de de kronik olarak aktive olmaktad\u0131r.
\nSiklopamin (Cyc) bir steroid alkaloid ve Hh sinyal yolunun bir inhibit\u00f6r\u00fcd\u00fcr. SMO'nun uzaysal konformasyonunu de\u011fi\u015ftirerek, SMO'nun aktivitesi, Hh sinyal yolunun a\u015fa\u011f\u0131 ak\u0131\u015f sinyal iletimini bast\u0131rmak i\u00e7in inhibe edilir ve b\u00f6ylece Hh yolunu inhibe edilmi\u015f bir duruma getirir. Cyc, t\u00fcm\u00f6r genlerinin transkripsiyonunu ve ekspresyonunu inhibe edebilir, SHH arac\u0131l\u0131 Hh sinyal yoluna m\u00fcdahale edebilir, anti-t\u00fcm\u00f6r ve anti PF etkileri uygulayabilir ve b\u00f6ylece ilgili hastal\u0131klar\u0131n ilerlemesini engelleyebilir. \u0130lgili \u00e7al\u0131\u015fmalar, Hh sinyal yolundaki SMO proteinlerine ba\u011flanarak ve SMO proteinlerinin a\u015fa\u011f\u0131 y\u00f6nl\u00fc sinyal iletimini etkileyerek, \u03b1 - SMA ve kolajen tip 1 (Col-1) proteinlerinin ekspresyonunun azalt\u0131labilece\u011fini, b\u00f6ylece y\u00fcksek hassasiyetli C-reaktif proteindeki bu de\u011fi\u015fikli\u011fi zay\u0131flatabilece\u011fini veya hatta \u00f6nleyebilece\u011fini ve portal hipertansiyonu iyile\u015ftirebilece\u011fini g\u00f6stermi\u015ftir. Ayr\u0131ca, Hh sinyalizasyonuna m\u00fcdahale eden Cyc gibi ila\u00e7lar, prostat kanseri h\u00fccrelerinde androjen direncini ve hastal\u0131\u011f\u0131n ilerlemesini \u00f6nlemeye yard\u0131mc\u0131 olabilir. Hh sinyal yolu hastal\u0131klar\u0131n olu\u015fumunu ve geli\u015fimini etkiler, ancak Cyc'in PF ile ilgili hastal\u0131klardaki rol\u00fc hala belirsizdir.
\nDracocephalum moldevica L. t\u00fcm otlaklarda ila\u00e7 olarak kullan\u0131lan Labiatae familyas\u0131na ait bir bitkidir. Ba\u015fl\u0131ca kimyasal bile\u015fenleri u\u00e7ucu ya\u011f, polisakkarit, terpenoidler, flavonoidler, amino asitler ve eser elementlerdir. Kardiyovask\u00fcler ve serebrovask\u00fcler damarlar\u0131 koruma, anti ateroskleroz, anti ast\u0131m, \u0131s\u0131y\u0131 temizleme ve detoksifikasyon, kan dola\u015f\u0131m\u0131n\u0131 te\u015fvik etme ve kollaterallerin blokaj\u0131n\u0131 kald\u0131rma, antioksidan, dislipidemiyi d\u00fczenleme, ayr\u0131ca r\u00fczgar ve \u0131s\u0131y\u0131 temizleme, so\u011fuk alg\u0131nl\u0131\u011f\u0131 ve ate\u015f, \u00f6ks\u00fcr\u00fck ve ast\u0131m gibi \u00e7e\u015fitli farmakolojik etkilere sahiptir. Ara\u015ft\u0131rmalar, Xiangqinglan'\u0131n toplam 41 flavonoid i\u00e7erdi\u011fini ve Xiangqinglan'\u0131n t\u0131bbi \u00f6zelliklerinin esas olarak flavonoidlerden geldi\u011fini bulmu\u015ftur. \u00d6nceki \u00e7al\u0131\u015fmalar, Xiangqinglan'\u0131n ana aktif bile\u015fenlerinden biri olan TFDM'nin \u00f6ks\u00fcr\u00fck ve ast\u0131m\u0131 hafifletmede \u00e7ok etkili bir etkiye sahip oldu\u011funu g\u00f6stermi\u015ftir. Farelerin hava yollar\u0131 i\u00e7indeki y\u00fcksek reaktiviteyi \u00f6nemli \u00f6l\u00e7\u00fcde yava\u015flatabilir ve b\u00f6ylece akci\u011fer fonksiyon hasar\u0131n\u0131 onarabilir. Farelerde interl\u00f6kin-6 (IL-6), interl\u00f6kin-17 (IL-17) ve t\u00fcm\u00f6r nekroz fakt\u00f6r\u00fc - \u03b1 (TNF - \u03b1) sal\u0131n\u0131m\u0131, interl\u00f6kin-4 (IL-4) ile interferon - \u03b3 (IFN - \u03b3) oran\u0131n\u0131 \u00f6nemli \u00f6l\u00e7\u00fcde azaltarak Th1\/Th2 ba\u011f\u0131\u015f\u0131kl\u0131k dengesizli\u011fini ayarlar. Bunlar aras\u0131nda TFDM, akci\u011fer dokusundaki Col-1 i\u00e7eri\u011fini azaltarak NOD benzeri resept\u00f6r termal protein alan\u0131 ile ili\u015fkili protein 3'\u00fcn (NL-RP3) ekspresyonunu kontrol edebilir ve sonu\u00e7ta pulmoner fibrozu hafifletme hedefine ula\u015fabilir. Ve \u00f6nceki \u00e7al\u0131\u015fmalar Dracocephalum moldavica L.'den (TFDM) elde edilen toplam flavonoidlerin, Hh sinyal yola\u011f\u0131ndaki SHH, Ptch1, SMO, SUFU, Gli1 gibi \u00f6nemli d\u00fczenleyici proteinleri a\u015fa\u011f\u0131 veya yukar\u0131 d\u00fczenleyerek bleomisinin neden oldu\u011fu PF'yi etkili bir \u015fekilde hafifletebilece\u011fini g\u00f6stermi\u015ftir. Bu nedenle, bu makale Cyc ve TFDM'nin Hh sinyal yola\u011f\u0131na dayal\u0131 olarak PF \u00fczerindeki etki mekanizmas\u0131n\u0131 incelemektedir.<\/p>\n

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\nErken a\u015famada Xiangqinglan \u00fczerinde b\u00fcy\u00fck miktarda ara\u015ft\u0131rma yap\u0131lm\u0131\u015f ve optimum ekstraksiyon s\u00fcreci belirlenmi\u015ftir. Xiangqinglan \u00f6z\u00fct\u00fc, Xiangqinglan'\u0131n etkili k\u0131s\u0131mlar\u0131n\u0131 elde etmek i\u00e7in makro g\u00f6zenekli adsorpsiyon re\u00e7inesi kullan\u0131larak safla\u015ft\u0131r\u0131ld\u0131. Xiangqinglan'\u0131n etkili k\u0131s\u0131mlar\u0131 ayr\u0131\u015ft\u0131r\u0131ld\u0131 ve tan\u0131mlama i\u00e7in yap\u0131sal olarak analiz edildi. Bundan \u00f6nce, Xiangqinglan'\u0131n etkili k\u0131s\u0131mlar\u0131n\u0131n i\u00e7eri\u011fi belirlenmi\u015f ve klinik doza dayal\u0131 olarak, ilgili literat\u00fcre g\u00f6re hayvan\u0131n in vivo dozaj\u0131na d\u00f6n\u00fc\u015ft\u00fcr\u00fclm\u00fc\u015ft\u00fcr. \u00d6nceki \u00e7al\u0131\u015fmalarda, PF fare modellerinde TFDM'nin (90, 180, 360mg\/kg) ilgili dozlar\u0131n\u0131n etki mekanizmas\u0131 Hh sinyal yola\u011f\u0131na dayal\u0131 olarak ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. PF fare modelinde Hh sinyal yolunun aktive oldu\u011fu ve TFDM'nin Hh sinyal yolunun \u00f6nemli d\u00fczenleyici proteinlerine m\u00fcdahale ederek PF'yi iyile\u015ftirebilece\u011fi ve y\u00fcksek TFDM dozlar\u0131nda (360mg\/kg) daha belirgin bir etki g\u00f6zlendi\u011fi bulunmu\u015ftur.
\nBu nedenle, \u00f6nceki ara\u015ft\u0131rmalara dayanarak, bu makale bleomisin ile ind\u00fcklenen PF farelerinde Cyc taraf\u0131ndan Hh sinyal yolunun inhibisyonunu ve TFDM'nin (360mg\/kg) ilgili etkilerini ara\u015ft\u0131rmaya odaklanmaktad\u0131r. Bleomisinin intratrakeal instilasyonu ile bir PF fare modeli olu\u015fturulmu\u015ftur. Modelin olu\u015fturulmas\u0131n\u0131n ikinci g\u00fcn\u00fcnde, farelere Cyc ve TFDM gibi ilgili ila\u00e7lar oral yoldan uygulanm\u0131\u015ft\u0131r. Cyc ve TFDM ila\u00e7lar\u0131n\u0131n \u00e7\u00f6z\u00fcnmezli\u011fi nedeniyle, 0.5% karboksimetil sel\u00fcloz sodyum ilgili s\u00fcspansiyon olarak haz\u0131rland\u0131 ve gavaj yoluyla uyguland\u0131.
\nPF modelinin olu\u015fturulmas\u0131n\u0131n ilk a\u015famas\u0131nda, hastal\u0131kl\u0131 fareler kilo kayb\u0131, i\u015ftah kayb\u0131, da\u011f\u0131n\u0131k k\u00fcrk rengi ve k\u00f6t\u00fc zihinsel durum gibi semptomlar ve \u00e7ok say\u0131da \u00f6l\u00fcm g\u00f6sterdi. Ayn\u0131 zamanda, HE ve Masson boyal\u0131 akci\u011fer dokusu patolojik kesitlerinin sonu\u00e7lar\u0131na dayanarak, PF modelinin yap\u0131m\u0131n\u0131n ba\u015far\u0131l\u0131 oldu\u011fu sonucuna var\u0131lm\u0131\u015ft\u0131r. S\u00fcrekli ila\u00e7 m\u00fcdahalesinden sonra, PF modeli yap\u0131m\u0131n\u0131n sonraki a\u015famas\u0131nda farelerin \u00e7e\u015fitli semptomlar\u0131 \u00f6nemli \u00f6l\u00e7\u00fcde iyile\u015fmi\u015ftir. Akci\u011fer dokusu patolojik kesitlerinin sonu\u00e7lar\u0131, Cyc grubu ve TFDM grubunun akci\u011fer doku yap\u0131s\u0131n\u0131n normal oldu\u011funu ve enflamatuar h\u00fccrelerin ve fibrotik dokunun \u00f6nemli \u00f6l\u00e7\u00fcde azald\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015ftir. Daha sonra, HYP i\u00e7eri\u011fi \u00f6l\u00e7\u00fclm\u00fc\u015f ve ara\u015ft\u0131rma sonu\u00e7lar\u0131 model grubundaki HYP i\u00e7eri\u011finin artt\u0131\u011f\u0131n\u0131, Cyc grubu ve TFDM grubunun ise HYP i\u00e7eri\u011fini \u00f6nemli \u00f6l\u00e7\u00fcde azaltabildi\u011fini g\u00f6stermi\u015ftir. PF'nin klinik belirtileri, k\u00f6t\u00fcle\u015fen akci\u011fer hasar\u0131n\u0131n e\u015flik etti\u011fi, akci\u011fer fonksiyonlar\u0131nda s\u00fcrekli bir d\u00fc\u015f\u00fc\u015fle sonu\u00e7lanan ve nihayetinde \u00f6l\u00fcme yol a\u00e7an inat\u00e7\u0131 kuru \u00f6ks\u00fcr\u00fck ve akut solunum s\u0131k\u0131nt\u0131s\u0131d\u0131r. PF, ilerleyici solunum s\u0131k\u0131nt\u0131s\u0131 ile karakterize, gaz de\u011fi\u015fim bozukluklar\u0131na ve k\u0131s\u0131tlay\u0131c\u0131 ventilasyon sorunlar\u0131na yol a\u00e7an akci\u011fer fonksiyon kayb\u0131na neden olabilir. Bu nedenle, bu \u00e7al\u0131\u015fmada solunum fonksiyon testleri yap\u0131lm\u0131\u015f ve Cyc grubu ile TFDM grubunun PF hava ak\u0131m\u0131 s\u0131n\u0131rlamas\u0131n\u0131 iyile\u015ftirebildi\u011fi ve RL, RE ve FEV0.1\/FVC'yi azalt\u0131rken Cdyn, FVC ve PEF'yi art\u0131rarak k\u0131s\u0131tlay\u0131c\u0131 ventilasyon i\u015flev bozuklu\u011funu hafifletebildi\u011fi ve bleomisin kaynakl\u0131 PF semptomlar\u0131n\u0131 etkili bir \u015fekilde hafifletti\u011fi bulunmu\u015ftur.
\nHh yolu, PF'yi kontrol etmek i\u00e7in ECM salg\u0131lanmas\u0131 ve metabolizmas\u0131 gibi PF s\u00fcrecinde \u00f6nemli bir rol oynar. Hh sinyal yolu ligandlar\u0131n salg\u0131lanmas\u0131yla ba\u015flat\u0131l\u0131r ve Ptch SMO \u00fczerindeki inhibit\u00f6r etkiyi ortadan kald\u0131rarak transkripsiyon fakt\u00f6r\u00fc Gli1'in aktivasyonunu ve n\u00fckleer translokasyonu te\u015fvik ederek Gli1 ve SMO gibi Hh hedef genlerinin ekspresyonuna yol a\u00e7ar. Bu nedenle, mevcut \u00e7al\u0131\u015fmada, SMO inhibit\u00f6r\u00fc Cyc, TFDM'nin PF farelerindeki rol\u00fcn\u00fc belirlemek i\u00e7in Hh yolunu inhibe etmek i\u00e7in kullan\u0131lm\u0131\u015ft\u0131r. Bu \u00e7al\u0131\u015fmada Col-1, \u03b1 - SMA, FN1, SHH, SMO, SUFU, Gli1, vb. gibi ilgili proteinler tespit edilmi\u015ftir. Hh yola\u011f\u0131n\u0131n Cyc ve TFDM inhibisyonu ECM \u00fcretimini ve anjiyogenezi inhibe edebilir; bu da Col-1, \u03b1 - SMA, FN1, SHH, SMO, Gli1 gibi ilgili proteinlerin a\u015fa\u011f\u0131 reg\u00fclasyonu ve SUFU proteininin yukar\u0131 reg\u00fclasyonu ile sa\u011flanabilir. Bu da PF'nin Hh sinyal yolunun inhibisyonu ile ili\u015fkili oldu\u011funu do\u011frulamaktad\u0131r. Hem Cyc grubu hem de TFDM grubu akci\u011fer dokusu hasar\u0131n\u0131 onarabilmi\u015f, kolajen lif i\u00e7eri\u011fini iyile\u015ftirebilmi\u015f, Hh sinyal yola\u011f\u0131 ile ilgili protein i\u00e7eri\u011fini a\u015fa\u011f\u0131 veya yukar\u0131 d\u00fczenleyebilmi\u015f ve b\u00f6ylece akci\u011fer dokusu fibrozunun ilerlemesini hafifletmi\u015ftir. Dahas\u0131, Cyc ve TFDM kombinasyonu daha iyi etkinlik g\u00f6stermi\u015ftir.
\n\u00d6zetle, bu makale PF'nin olu\u015fumu ve geli\u015fimi hakk\u0131nda daha ayr\u0131nt\u0131l\u0131 bilgi vermekte ve TFDM'nin belirli bir terap\u00f6tik etkiye sahip oldu\u011funu do\u011frulamaktad\u0131r. Ayr\u0131ca, PF ile ilgili Hh sinyal yolunun etki mekanizmas\u0131n\u0131 inceleyerek, PF'nin ilgili etki mekanizmalar\u0131n\u0131n incelenmesi i\u00e7in iyi bir ara\u015ft\u0131rma temeli sa\u011flamaktad\u0131r.<\/p>","protected":false},"excerpt":{"rendered":"

The effect of the combination therapy of licorice cyclopamine and total flavonoids of fragrant orchid on pulmonary fibrosis mice Pulmonary fibrosis (PF) is a chronic progressive lung disease with obvious histopathological patterns, including a large number of chronic respiratory system lesions, accompanied by the growth of connective tissue in various pulmonary compartments. Among them, interstitial […]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\nThe effect of the combination therapy of licorice cyclopamine and total flavonoids of fragrant orchid on pulmonary fibrosis mice - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/tr\/siklopamin\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The effect of the combination therapy of licorice cyclopamine and total flavonoids of fragrant orchid on pulmonary fibrosis mice - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"The effect of the combination therapy of licorice cyclopamine and total flavonoids of fragrant orchid on pulmonary fibrosis mice Pulmonary fibrosis (PF) is a chronic progressive lung disease with obvious histopathological patterns, including a large number of chronic respiratory system lesions, accompanied by the growth of connective tissue in various pulmonary compartments. 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