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Kafukufuku wosiyanasiyana wopangidwa ndi Eustachian chubu (ET) stent akuchitika, koma sanagwiritsidwebe ntchito pazachipatala. M'maphunziro a preclinical, ma scaffolds a ET adangowonjezera kuchuluka kwa minofu yopangidwa ndi scaffold. Kuchita bwino kwa cobalt-chromium sirolimus-eluting stent (SES) poletsa kuchulukana kwa minofu yopangidwa ndi stent pambuyo poyika stent idaphunziridwa mu mtundu wa porcine ET. Nkhumba zisanu ndi chimodzizo zinagawidwa m'magulu awiri (ie gulu lolamulira ndi gulu la SES) ndi nkhumba zitatu pagulu lililonse. Gulu loyang'anira lidalandira cobalt-chromium stent (n = 6), ndipo gulu la SES lidalandira cobalt-chromium stent yokhala ndi zokutira sirolimus-eluting (n = 6). Magulu onse adaperekedwa nsembe masabata a 4 pambuyo poyika stent. Kuyika kwa stent kunali kopambana mu ma ET onse popanda zovuta zokhudzana ndi opaleshoni. Palibe ma stents omwe amatha kukhalabe ndi mawonekedwe ake ozungulira, ndipo kuchulukana kwa ntchentche kunkawoneka mkati ndi mozungulira ma stents m'magulu onsewa. Kusanthula kwa histological kunawonetsa kuti gawo la kuchuluka kwa minofu ndi makulidwe a submucosal fibrosis mu gulu la SES anali otsika kwambiri kuposa gulu lowongolera. SES ikuwoneka kuti ndiyothandiza poletsa kuchulukana kwa minofu yopangidwa ndi scaffold mu nkhumba za ET. Komabe, maphunziro owonjezera amafunikira kuti atsimikizire zida zoyenera za ma stents ndi antiproliferative mankhwala.
Eustachian chubu (ET) ali ndi ntchito zofunika pakati khutu (mwachitsanzo, mpweya wabwino, kuteteza kusamutsa tizilombo toyambitsa matenda ndi secretions ku nasopharynx)1. Zimaphatikizanso chitetezo ku phokoso la nasopharyngeal ndi regurgitation2. ET nthawi zambiri imatsekedwa, koma imatsegulidwa ndi kumeza, kuyasamula, kapena kutafuna. Komabe, vuto la ET likhoza kuchitika ngati chubu sichitsegula kapena kutseka bwino3,4. Dilated (obstructive) dysfunction ya ET depresses ET ntchito ndipo, ngati ntchitozi sizikusungidwa, zimatha kukhala zovuta kapena zosatha za otitis media, imodzi mwa matenda omwe amapezeka kwambiri muzochita za ENT. Mankhwala amakono a vuto la ET (mwachitsanzo, opaleshoni ya m'mphuno, kuika mpweya wabwino, ndi mankhwala) amagwiritsidwa ntchito kwa odwala. Komabe, mankhwalawa ali ndi mphamvu zochepa ndipo angayambitse kutsekeka kwa ET, matenda, ndi tympanic membrane perforation3,6,7 yosasinthika. Eustachian chubu balloon angioplasty idayambitsidwa ngati njira ina yochizira kusagwira bwino ntchito kwa ET8. Ngakhale kuti maphunziro angapo kuyambira 2010 awonetsa kuti kukonza baluni ya Eustachian chubu ndipamwamba kuposa chithandizo chodziwika bwino cha vuto la ET, odwala ena samayankha dilatation8,9,10,11. Choncho, stenting ikhoza kukhala njira yothandizira12,13. Ngakhale maphunziro ambiri opitilira apo akuwunika kuthekera kwaukadaulo ndi kuyankha kwa minofu pambuyo poyika stent ku ET, hyperplasia yopangidwa ndi stent chifukwa cha kuwonongeka kwamakina imakhalabe vuto lalikulu la postoperative 14,15,16,17,18,19. mankhwala, odzaza ndi antiproliferative agents kusintha izi.
Ma stents otulutsa mankhwala akhala akugwiritsidwa ntchito kuletsa stent restenosis yomwe imayambitsidwa ndi minofu ndi neointimal hyperplasia pambuyo poyika stent. Nthawi zambiri, scaffolds kapena zomangira zimakutidwa ndi mankhwala (mwachitsanzo, everolimus, paclitaxel, ndi sirolimus)20,23,24. Sirolimus ndi mankhwala oletsa kufalikira kwa maselo omwe amalepheretsa masitepe angapo a restenosis cascade (mwachitsanzo, kutupa, neointimal hyperplasia, ndi collagen synthesis)25. Chifukwa chake, kafukufukuyu adaganiza kuti ma stents okutidwa ndi sirolimus amatha kupewa hyperplasia ya stent-induced tissue hyperplasia mu ET nkhumba (Chithunzi 1). Cholinga cha phunziroli chinali kufufuza mphamvu ya sirolimus-eluting stents (SES) poletsa kuchulukana kwa minofu yopangidwa ndi stent pambuyo poyika stent mu chitsanzo cha porcine ET.
Chithunzi chojambula cha cobalt-chromium sirolimus-eluting stent (SES) pochiza matenda a Eustachian chubu, kusonyeza kuti sirolimus-eluting stent imalepheretsa kuchulukana kwa minofu yopangidwa ndi stent.
Cobalt-chromium (Co-Cr) aloyi stents anapangidwa ndi laser kudula Co-Cr aloyi machubu (Genoss Co., Ltd., Suwon, Korea). Pulatifomu ya stent imagwiritsa ntchito chomangira chawiri chotseguka chokhala ndi zomanga zolumikizana kuti zitheke kusinthasintha kwakukulu ndi mphamvu yabwino ya radial, kufupikitsa ndi kutsata. Chophimbacho chinali ndi mainchesi a 3 mm, kutalika kwa 18 mm, ndi makulidwe a 78 µm (mkuyu 2a). Miyeso ya chimango cha Co-Cr alloy idatsimikiziridwa kutengera kafukufuku wathu wam'mbuyomu.
Cobalt-chromium (Co-Cr) aloyi stent ndi chitsulo chowongolera sheath poyika ma chubu a Eustachian. Zithunzizi zikuwonetsa (a) stent ya Co-Cr alloy ndi (b) catheter yotchingidwa ndi baluni. (c) Katheta ya baluni ndi stent zayikidwa kwathunthu. (d) Chitsulo chowongolera zitsulo chinapangidwira chitsanzo cha chubu cha nkhumba cha Eustachian.
Sirolimus ntchito pamwamba pa stent ntchito akupanga kutsitsi luso. SES idapangidwa kuti itulutse pafupifupi 70% ya mankhwala oyambira (1.15 µg/mm2) mkati mwa masiku 30 oyamba atayikidwa. Chophimba chocheperako kwambiri cha 3 µm chimayikidwa kumbali yakutsogolo ya stent kuti mukwaniritse zomwe mukufuna kutulutsa mankhwala ndikuchepetsa kuchuluka kwa polima; ❖ kuyanika kwa biodegradable kumeneku kuli ndi copolymer ya lactic ndi glycolic acid ndi eni ake osakaniza a poly(1) -lactic acid)26,27. Co-Cr aloyi stents anali crimped pa baluni catheters 3 mm m'mimba mwake ndi 28 mm kutalika (Genoss Co., Ltd.; Mku. 2b). Ma stents awa amapezeka ku South Korea pochiza matenda amtima.
Chigoba chowongolera chatsopano chachitsulo cha nkhumba ET chitsanzo chinapangidwa ndi chitsulo chosapanga dzimbiri (mkuyu 2c). Ma diameter amkati ndi akunja a chipolopolo ndi 2 mm ndi 2.5 mm, motero, kutalika kwake ndi 250 mm. Dera lakutali la 30 mm sheath lidapindika mu mawonekedwe a J pamakona a 15 ° kupita ku axis kuti alole kupeza mosavuta kuchokera kumphuno kupita ku nasopharyngeal orifice ya ET mu chitsanzo cha nkhumba.
Kafukufukuyu adavomerezedwa ndi Komiti ya Institutional Animal Care and Use Committee ya Asan Institute of Life Sciences (Seoul, South Korea) ndipo ikugwirizana ndi National Institutes of Health Guidelines for the Humane Treatment of Laboratory Animals (IACUC-2020-12-189). . Kafukufukuyu adachitika motsatira malangizo a ARRIVE. Phunziroli linagwiritsa ntchito 12 ETs mu nkhumba za 6 zolemera 33.8-36.4 kg pa miyezi itatu. Nkhumba zisanu ndi chimodzizo zinagawidwa m'magulu awiri (ie gulu lolamulira ndi gulu la SES) ndi nkhumba zitatu pagulu lililonse. Gulu loyang'anira lidalandira stent ya Co-Cr alloy osatsekedwa, pomwe gulu la SES lidalandira Co-Cr alloy stent eluting sirolimus. Nkhumba zonse zinali ndi mwayi wopeza madzi ndi chakudya chaulere ndipo zinkasungidwa pa 24 ° C ± 2 ° C kwa maola a 12 masana usiku. Pambuyo pake, nkhumba zonse zinaperekedwa nsembe kwa masabata a 4 pambuyo poyika stent.
Nkhumba zonse zinalandira zosakaniza za 50mg/kg zolazepam, 50mg/kg teletamide (Zoletil 50; Virbac, Carros, France) ndi 10mg/kg xylazine (Rompun; Bayer HealthCare, Les Varkouzins, Germany). ndiye chubu cha tracheal chinayikidwa ndi inhalation ya 0.5-2% isoflurane (Ifran®; Hana Pharm. Co., Seoul, Korea) ndi oxygen 1: 1 (510 ml / kg / min) kwa anesthesia. Nkhumba zinayikidwa pa malo a supine ndi endoscopy yoyambira (VISERA 4K UHD rhinolaryngoscope; Olympus, Tokyo, Japan) inachitidwa kuti ifufuze orifice ya nasopharyngeal ya ET. Chombo chowongolera chitsulo chinapititsidwa patsogolo kupyolera mumphuno kupita ku nasopharyngeal orifice ya ET pansi pa endoscopic control (Mkuyu 3a, b). Catheter ya baluni, stent ya corrugated, imalowetsedwa kupyolera mu introducer mu ET mpaka nsonga yake ikukumana ndi kukana mu osteochondral isthmus ya ET (Mkuyu 3c). Catheter ya baluni inali yodzaza ndi saline ku 9 atmospheres, monga momwe zimakhalira ndi manometer monitor (mkuyu 3d). Catheter ya baluni inachotsedwa pambuyo poyika stent (mkuyu 3f), ndipo kutsegula kwa nasopharyngeal kunayesedwa mosamala endoscopy chifukwa cha zovuta za opaleshoni (mkuyu 3f). Nkhumba zonse zidachitidwa ndi endoscopy isanayambe komanso itangotha ​​kumene, komanso masabata a 4 pambuyo pa stenting, kuti awone momwe malo a stent alili komanso zozungulira zozungulira.
Masitepe aukadaulo pakuyika stent mu chubu cha eustachian (ET) cha nkhumba pansi pa endoscopic control. (a) Chithunzi cha endoscopic chosonyeza kutsegula kwa nasopharyngeal (muvi) ndi cholozera chachitsulo cholowetsamo (muvi). (b) Kulowetsa mchimake wachitsulo (muvi) pabowo la nasopharyngeal. (c) Katheta ya baluni yokhomerera (muvi) imalowetsedwa mu ET kudzera mu sheath (muvi). (d) Katheta wa baluni (muvi) watenthedwa. (e) Mapeto oyandikira a stent amachokera ku ET orifice ya nasopharynx. (f) Chithunzi cha endoscopic chowonetsa stent lumen patency.
Nkhumba zonse zidathandizidwa popereka 75 mg/kg potaziyamu kloride ndi jekeseni wa mtsempha wa khutu. Zigawo zapakati za sagittal za mutu wa nkhumba zinkagwiritsidwa ntchito pogwiritsa ntchito chainsaw yotsatiridwa ndi kuchotsedwa mosamala kwa ET scaffold tissue samples pofuna kufufuza kwake kwa histological (Supplementary Fig. 1a, b). Zitsanzo za minofu ya ET zidakhazikitsidwa mu 10% osalowerera ndale formalin kwa maola 24.
Zitsanzo za minofu ya ET zidatsitsidwa motsatizana ndi mowa wamitundu yosiyanasiyana. Zitsanzo zinayikidwa muzitsulo za resin polowetsa ndi ethylene glycol methacrylate (Technovit 7200® VLC; Heraus Kulzer GMBH, Wertheim, Germany). Zigawo za Axial zinkachitidwa pazitsulo zamtundu wa ET zophatikizidwa m'magawo a proximal ndi distal (Supplementary Fig. 1c). Kenako midadada ya polima idayikidwa pazithunzi zamagalasi a acrylic. Zithunzi za resin block slide zinali microground ndikupukutidwa ndi pepala la silicon carbide la makulidwe osiyanasiyana mpaka makulidwe a 20 µm pogwiritsa ntchito grid system (Apparatebau GMBH, Hamburg, Germany). Ma slide onse adayesedwa ku histological ndi hematoxylin ndi eosin madontho.
Kuwunika kwa histological kunachitika kuti awone kuchuluka kwa kuchuluka kwa minofu, makulidwe a submucosal fibrosis, ndi kuchuluka kwa kulowa kwa cell yotupa. Kuchuluka kwa minofu hyperplasia yokhala ndi gawo lopapatiza la ET idawerengedwa pothetsa equation:
Kuchuluka kwa submucosal fibrosis kumayesedwa molunjika kuchokera ku stent struts kupita ku submucosa. Mlingo wa kulowetsedwa kwa maselo otupawo unaweruzidwa mwapadera ndi kugawa ndi kuchuluka kwa maselo otupa, omwe ndi: digiri ya 1 (yofatsa) - kulowetsedwa kwa leukocyte imodzi; Digiri ya 2 (yofatsa mpaka yocheperako) - kulowetsedwa kwa leukocyte kokhazikika; Digiri ya 3 (yapakati) - kuphatikiza. ndi ma leukocyte osatha kusiyanitsa pakati pa loci payekha; kalasi ya 4 (yapakati mpaka yoopsa) ma leukocyte amafalikira kulowa mu submucosa yonse, ndipo kalasi ya 5 (yoopsa) imafalitsa kulowetsedwa ndi ma multiplefoci a necrosis. Kuchuluka kwa submucosal fibrosis ndi kuchuluka kwa kulowetsedwa kwa maselo otupa kunapezedwa ndi pafupifupi mfundo zisanu ndi zitatu kuzungulira circumference. Kusanthula kwa histological kwa ET kunkachitika pogwiritsa ntchito microscope (BX51; Olympus, Tokyo, Japan). Miyezoyo inapezedwa pogwiritsa ntchito pulogalamu ya CaseViewer (CaseViewer; 3D HISTECH Ltd., Budapest, Hungary). Kusanthula kwa deta ya histological kunachokera ku mgwirizano wa owona atatu omwe sanatenge nawo mbali mu phunziroli.
Mayeso a Mann-Whitney U adagwiritsidwa ntchito kupenda kusiyana pakati pa magulu ngati pakufunika. A p <0.05 idawonedwa ngati yofunika kwambiri. A p <0.05 idawonedwa ngati yofunika kwambiri. Значение p < 0,05 считалось статистически значимым. Mtengo wa p <0.05 unkawoneka ngati wofunikira kwambiri. p <0.05 被认为具有统计学意义. pa <0.05 p <0,05 zithunzi zamtundu uliwonse. p <0.05 idawonedwa ngati yofunika kwambiri. Kuyesa kwa Bonferroni-kuwongolera kwa Mann-Whitney U-kunachitidwa pa ma p values ​​<0.05 kuti azindikire kusiyana kwamagulu (p <0.008 ngati kofunika kwambiri). Kuyesa kwa Bonferroni-kuwongolera kwa Mann-Whitney U-kunachitidwa pamtengo wa p <0.05 kuti azindikire kusiyana kwamagulu (p <0.008 monga mwachiwerengero). U-критерий Манна-Уитни правкой pa Бонферрони был выполнен для значений p <0,05 mpaka выявления групповых различи00 (p08, p. значимое). Mayeso a Bonferroni-adjusted Mann-Whitney U adachitidwa pa ma p values ​​​​<0.05 kuti azindikire kusiyana kwamagulu (p <0.008 monga kufunikira kowerengera).对p 值< 0.05 进行Bonferroni 校正的Mann-Whitney U 检验以检测组差异（p <0.008 具有统计学意义）.对p 值< 0.05 进行Bonferroni 校正的Mann-Whitney U U-критерий Манна-Уитни правкой pa Бонферрони был выполнен для значений p <0,05 mpaka выявления групповых различы0,0 p8 значимыm). Bonferroni-adjusted Mann-Whitney U-mayeso anachitidwa kwa p <0.05 kuti azindikire kusiyana kwamagulu (p <0.008 inali yofunikira kwambiri).Kusanthula kowerengera kunachitika pogwiritsa ntchito pulogalamu ya SPSS (mtundu wa 27.0; SPSS, IBM, Chicago, IL, USA).
Kuyika konse kwa nkhumba za nkhumba kunali kopambana mwaukadaulo. Chombo chowongolera zitsulo chinayikidwa bwino mu nasopharyngeal orifice ya ET pansi pa endoscopic control, ngakhale kuvulala kwa mucosal ndi kutuluka kwa magazi kunkawoneka mu 4 ya zitsanzo za 12 (33.3%) panthawi yoyika zitsulo. Patatha milungu inayi, kutuluka kwa magazi mkokomoko kunasiya. Nkhumba zonse zidapulumuka mpaka kumapeto kwa phunziroli popanda zovuta zokhudzana ndi stent.
Zotsatira za endoscopy zikuwonetsedwa mu Chithunzi 4. Pakutsata kwa masabata a 4, ma stents anakhalabe mu nkhumba zonse. Kuchulukana kwa ntchentche mkati ndi kuzungulira ET stent kunawonedwa mu onse (100%) ET mu gulu lolamulira ndi atatu (50%) a asanu ndi limodzi a ET mu gulu la SES, ndipo panalibe kusiyana pakati pa magulu awiriwa (p = 0.182). Palibe ma stenti omwe adayikidwa omwe amatha kukhala ozungulira.
Zithunzi za Eustachian chubu (ET) za nkhumba mu gulu lolamulira ndi gulu lomwe lili ndi cobalt-chromium stent (CXS) eluting sirolimus. (a) Chithunzi choyambirira cha endoscopic chojambulidwa asanaikidwe stent chosonyeza kutsegula kwa nasopharyngeal (muvi) wa ET. (b) Chithunzi cha Endoscopic chojambulidwa atangoyika stent kuwonetsa ET ya kuyika kwa stent. Kutuluka kwa magazi kumawonedwa chifukwa cha chitsulo chowongolera (muvi). (c) Chithunzi cha Endoscopic chomwe chatengedwa masabata a 4 pambuyo poyika stent chikuwonetsa ntchofu kuzungulira stent (muvi). (d) Chithunzi cha Endoscopic chosonyeza kuti stent singakhale wozungulira (muvi).
Zotsatira za histological zikuwonetsedwa mu Chithunzi 5 ndi Supplementary Figure 2. Kuchulukana kwa minofu ndi kufalikira kwa submucosal fibrous pakati pa stent posts mu ET lumen ya magulu onse awiri. Chiwerengero chapakati cha minofu ya hyperplasia m'derali chinali chachikulu kwambiri mu gulu lolamulira kusiyana ndi gulu la SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Chiwerengero chapakati cha minofu ya hyperplasia m'derali chinali chachikulu kwambiri mu gulu lolamulira kusiyana ndi gulu la SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Средний процент площади гиперплазии тканей был значительно больше в контрольной группе, чем в группе СЭС (79,68% 48,36% ± 10,06%, p <0,001). Kuchuluka kwa chigawo cha minofu hyperplasia kunali kwakukulu kwambiri mu gulu lolamulira kusiyana ndi gulu la SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001).SES (79.48% ± 6.82% vs.48.36% ± 10.06%,p <0.001). 48.36% ± 10.06%,p <0.001). Средний процент площади гиперплазии тканей в контрольной группе был значительно выше, чем в группе СЭС (79,8,48,6% ± 10,06%, p <0,001). Kuchuluka kwa chigawo cha minofu hyperplasia mu gulu lolamulira kunali kwakukulu kwambiri kuposa gulu la SES (79.48% ± 6.82% vs. 48.36% ± 10.06%, p <0.001). Komanso, makulidwe amtundu wa submucosal fibrosis analinso apamwamba kwambiri mu gulu lolamulira kuposa gulu la SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001). Komanso, makulidwe amtundu wa submucosal fibrosis analinso apamwamba kwambiri mu gulu lolamulira kuposa gulu la SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001). Ndibwino kuti mukuwerenga, kufotokoza momveka bwino za фиброза также была значительно выше в контрольной группе, чем в группе СЭС 410, 50, 5, 6, 5, 5, 6 ± 0,20 мм, p <0,001). Komanso, makulidwe amtundu wa submucosal fibrosis analinso apamwamba kwambiri mu gulu lolamulira kuposa gulu la SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001).SES （1.41 ± 0.25 vs.0.56 ± 0.20 mm, p <0.001). 0.56±0.20mm,p<0.001). Кроме того, средняя толщина подслизистого фиброза в контрольной группе также была значительно выше, чем в группе СЭ0 ±25 ± 51 ± 51, 61 ± 1, 6 ± 0,20 мм, p <0,001). Kuonjezera apo, makulidwe amtundu wa submucosal fibrosis mu gulu lolamulira analinso apamwamba kwambiri kuposa gulu la SES (1.41 ± 0.25 vs. 0.56 ± 0.20 mm, p <0.001).Komabe, panalibe kusiyana kwakukulu pamlingo wa kulowetsedwa kwa maselo otupa pakati pa magulu awiriwa (gulu lolamulira [3.50 ± 0.55] vs. SES gulu [3.00 ± 0.89], p = 0.270).
Kusanthula kwa histological kufufuza kwa magulu awiri a stents omwe amaikidwa mu lumen ya Eustachian. (a, b) Dera la minofu hyperplasia (1 ya a ndi b) ndi makulidwe a submucosal fibrosis (2 ya a ndi b; mivi iwiri) anali okulirapo mu gulu lowongolera kuposa gulu la SES lokhala ndi strut stenting (madontho akuda), malo ocheperako lumen (wachikasu) ndi malo oyambira (ofiira). Mlingo wa kulowa kwa cell yotupa (3 ya a ndi b; mivi) sinali yosiyana kwambiri pakati pa magulu awiriwa. (c) Zotsatira za histological za gawo la minofu ya hyperplasia, (d) makulidwe a submucosal fibrosis, ndi (e) digiri ya kulowetsedwa kwa cell yotupa masabata a 4 pambuyo poyikidwa m'magulu onse awiri. SES, cobalt-chromium sirolimus eluting stent.
Mankhwala otulutsa mankhwala amathandizira kupititsa patsogolo mphamvu ya stent ndikupewa stent restenosis20,21,22,23,24. Kukhazikika kokhazikika kumabwera chifukwa cha kupangika kwa minofu ya granulation ndi kusintha kwa minofu yamitundu yosiyanasiyana yopanda mitsempha, kuphatikiza kummero, trachea, gastroduodenum, ndi bile. Mankhwala osokoneza bongo monga dexamethasone, paclitaxel, gemcitabine, EW-7197, ndi sirolimus amagwiritsidwa ntchito pamwamba pa waya wa waya kapena zokutira kuti ateteze kapena kuchiza hyperplasia ya minofu pambuyo poika stent29,30,34,35,36. Zatsopano zaposachedwa pazantchito zamatenda ophatikizika pogwiritsa ntchito ukadaulo wa fusion zikufufuzidwa mwachangu pochiza matenda osagwirizana ndi mitsempha37,38,39. Mu phunziro lapitalo mu chitsanzo cha porcine ET, kuwonjezeka kwa minofu yopangidwa ndi scaffold kunawonedwa. Ngakhale kukula kwa stent mu ET sikumveka bwino, kuyankha kwa minofu pambuyo poyikidwa kwa stent kwapezeka kuti kukufanana ndi ziwalo zina zopanda mitsempha za luminal19. Pakafukufuku wapano, SES idagwiritsidwa ntchito kuletsa kuchulukana kwa minofu yopangidwa ndi scaffold mu mtundu wa porcine ET. Sirolimus ndi poizoni ku ma islets a pancreatic ndi ma cell a beta, amachepetsa mphamvu zama cell ndikuwonjezera apoptosis40,41. Izi zingathandize kuletsa kufalikira kwa minofu mwa kuyambitsa kufa kwa maselo. Kafukufuku wathu adawonetsa kuti kugwiritsa ntchito koyamba kwa ma stents opangira mankhwala osokoneza bongo ku ET kunalepheretsa kufalikira kwa minofu yopangidwa ndi stent ku ET.
Chophimba chowonjezera cha Co-Cr chomwe chimagwiritsidwa ntchito mu phunziroli chimapezeka mosavuta chifukwa chimagwiritsidwa ntchito pochiza matenda a mitsempha ya m'mitsempha 42. Kuphatikiza apo, Co-Cr alloys ali ndi zida zamakina (mwachitsanzo, mphamvu zama radial ndi mphamvu zopanda inelastic) 43. Malingana ndi endoscopy ya kafukufuku wamakono, Co-Cr alloy stent yomwe imagwiritsidwa ntchito pa ET ya nkhumba sichikhoza kukhala ndi mawonekedwe ozungulira mu nkhumba zonse chifukwa cha kusakwanira kokwanira ndipo ilibe mphamvu yodzikulitsa. Mawonekedwe a stent olowetsedwa amathanso kusinthidwa ndikuyenda mozungulira ET ya nyama yamoyo (mwachitsanzo, kutafuna ndi kumeza). Mawonekedwe a makina a Co-Cr alloy stents akhala choyipa pakuyika kwa porcine ET stents. Kuphatikiza apo, kuyika kwa stent mu kasumbuko kungapangitse ET yotseguka kwamuyaya. ET yotseguka kapena yotalikirapo imalola kuti mawu ndi phokoso la nasopharyngeal, reflux ya m'mimba, ndi tizilombo toyambitsa matenda1 tipite pakati pa khutu lapakati, zomwe zimayambitsa kukwiya kwa mucosal ndi matenda. Chifukwa chake, mipata yokhazikika ya nasopharyngeal iyenera kupewedwa. Chifukwa chake, potengera kapangidwe ka ET cartilage, ma scaffolds amapangidwa makamaka kuchokera ku ma alloys amakumbukidwe okhala ndi zinthu zapamwamba kwambiri, monga nitinol. Nthawi zambiri, kutulutsa kolemera kumapezeka mkati ndi kuzungulira nasopharyngeal orifice ya stent. Popeza kuti kuyenda kwa mucociliary kwa ntchofu kumatsekedwa, chinsinsi chikuyembekezeka kudziunjikira m'mikwingwirima yotuluka kuchokera ku nasopharyngeal kutsegula. Kupewa kukwera kwa matenda a khutu lapakati ndi chimodzi mwa zolinga zazikulu za ET, ndikuyika ma stents omwe amatuluka kupitirira ET kuyenera kupewedwa, popeza kukhudzana kwachindunji kwa mabakiteriya ndi nasopharyngeal bacteria kungayambitse matenda okwera kwambiri.
Eustachian chubu balloon plasty kudzera pa nasopharyngeal kutsegula ndi njira yatsopano yochizira matenda a ET omwe cholinga chake ndi kutsegula ndi kukulitsa gawo la cartilaginous la ET8,9,10,46. Komabe, njira yochiritsira yochiritsira sichinadziwike47 ndipo zotsatira zake za nthawi yayitali zingakhale zochepa8,9,11,46. Pansi pazimenezi, kutsekemera kwachitsulo kwakanthawi kungakhale njira yabwino yothandizira odwala omwe samayankha kukonzanso ma baluni a chubu la Eustachian, ndipo kuthekera kwa ET stenting kwawonetsedwa m'maphunziro ambiri a preclinical. Poly-l-lactide scaffolds adayikidwa kudzera mu membrane ya tympanic mu chinchillas ndi akalulu kuti awone kulekerera ndi kuwonongeka kwa vivo17,18. Kuonjezera apo, chitsanzo cha nkhosa chinapangidwa kuti chiwunikire mbiri yazitsulo zazitsulo zowonjezera zowonjezera mu vivo. Mu phunziro lathu lapitalo, chitsanzo cha porcine ET chinapangidwa kuti chifufuze kuthekera kwaumisiri ndi kuwunika kwa zovuta zomwe zimayambitsidwa ndi stent, 19 kupereka maziko olimba a phunziroli kuti afufuze momwe SES ikuyendera pogwiritsa ntchito njira zomwe zakhazikitsidwa kale. Mu phunziro ili, SES idakhazikitsidwa bwino ku cartilage ndikuletsa kufalikira kwa minofu. Panalibe zovuta zokhudzana ndi stent, koma panali kuvulala kwa mucosal chifukwa cha chitsulo chowongolera sheath yokhala ndi magazi okhudzana ndi magazi omwe amatha mwadzidzidzi mkati mwa masabata a 4. Poganizira zovuta zomwe zingayambitse zitsulo zachitsulo, kukonza njira yobweretsera SES ndikofunikira komanso kofunikira.
Kafukufukuyu ali ndi malire. Ngakhale kuti zotsatira za histological zinali zosiyana kwambiri pakati pa magulu, chiwerengero cha zinyama mu phunziroli chinali chochepa kwambiri kuti chisawerengedwe chodalirika. Ngakhale owonera atatu adachititsidwa khungu kuti awone kusinthasintha kwapakati-observer, kuchuluka kwa submucosal yotupa cell infiltration idatsimikiziridwa payekhapayekha potengera kugawa ndi kuchuluka kwa maselo otupa chifukwa cha zovuta kuwerengera maselo otupa. Popeza phunziro lathu linkachitidwa pogwiritsa ntchito chiwerengero chochepa cha nyama zazikulu, mlingo umodzi wa mankhwalawa unagwiritsidwa ntchito, mu vivo maphunziro a pharmacokinetic sanachitidwe. Maphunziro ena amafunikira kuti atsimikizire mlingo woyenera wa mankhwalawa komanso chitetezo cha sirolimus mu ET. Pomaliza, nthawi yotsatiridwa ya masabata a 4 imakhalanso yochepetsera phunziroli, kotero maphunziro okhudza kugwira ntchito kwa nthawi yaitali kwa SES amafunika.
Zotsatira za kafukufukuyu zikuwonetsa kuti SES imatha kuletsa kufalikira kwa minofu yovulala pamakina pambuyo poyika ma baluni-expandable Co-Cr alloy scaffolds mu porcine ET model. Patatha milungu inayi pambuyo pa kuyika kwa stent, zosinthika zomwe zimagwirizanitsidwa ndi kuchulukana kwa minofu yopangidwa ndi stent (kuphatikiza gawo la kuchuluka kwa minofu ndi makulidwe a submucosal fibrosis) zinali zotsika kwambiri mu gulu la SES kuposa gulu lolamulira. SES ikuwoneka kuti ndiyothandiza poletsa kuchulukana kwa minofu yopangidwa ndi scaffold mu nkhumba za ET. Ngakhale kuti kafukufuku wowonjezereka akufunika kuti ayese zida zoyenera za stent ndi mlingo wa omwe akufuna mankhwala osokoneza bongo, SES ili ndi mphamvu zochiritsira zapafupi popewa ET tissue hyperplasia pambuyo poika stent.
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