MiRNK ifodasi diabetik buyrak kasalligiga qanday ta'sir qiladi?

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QISM Ⅱ: Diabetik buyrak kasalligida mikroRNK ifodasi profilini aniqlash

HIROKIISHII, SHOHEI KANEKO, KATSUNORI YANAl, AKINORI AOMATSU, KEIJ HIRAL, SUSUMU OOKAWARA, & YOSHIYUKI MORISHITA

ThemikroRNKlar (miRNKlar)tartibga solish mumkindiabetik buyrak kasalligi(DKD) to'liq tavsiflanmagan. Ushbu tadqiqotning maqsadi aniqlash edimiRNKlarbu DKD ta'sir qiladi(diabetik buyrak kasalligi)va maxsus biomarkerlar yoki terapevtik vositalar sifatida ishlatilishi mumkin. Birinchidan, ikkita DKD dan buyrak to'qimalari(diabetik buyrak kasalligi)sichqoncha modellari va boshqaruvchi sichqonlar farqlar uchun tekshirildimiRNKmikroarray tahlili orqali ifoda, so'ngra miqdoriy real vaqtda teskari transkripsiya-PCR. OltimiRNKlarikkala DKDda ham nazoratdan farqli ravishda ifodalangan(diabetik buyrak kasalligi)sichqoncha modellari. Ular orasida,miRNK-125b-5p va miRNK-181b-5p faqat ushbu davrda pasaytirildi.DKD(diabetik buyrak kasalligi)sichqoncha modeli. Keyinchalik, biz boshqardikmiRNKDKD ga -181b-5p-mimic(diabetik buyrakkasallik)sichqonlar, bu albuminuriya va anormal mezangial kengayishni kamaytiradi. Yo'llarni tahlil qilish va ma'lumotlar bazasini o'rganish shuni ko'rsatdiki, miRNK-181b-5p ning haddan tashqari ko'payishi DKD buyraklarida ma'lum bo'lgan oltita signal yo'lida etti mRNKning ifodasini sezilarli darajada o'zgartirgan.(diabetik buyrak kasalligi)sichqonlar. Bundan tashqari. qon zardobidagi miRNK-125b-5p darajasi DKD bilan og'rigan bemorlarda sezilarli darajada yuqori bo'lgan.(diabetik buyrak kasalligi)(1,89±{2}}.40-katta, P<0.05) compared="" with="" patients="" with="" other="" kidney="" diseases="" (0.94±0.13-fold)and="" healthy="" subjects(1.00±0.19-fold).serum="" levels="" of="" mirna-181b-5p="" were="" lower="" in="" patients="" with="">(diabetik buyrak kasalligi)({0}}.30±0.06-katlama, P<0.05)compared with="" patients="" with="" other="" kidney="" diseases(1.06±0.20-fold)and="" healthy="" subjects(1.00±0.16-fold).="" these="" results="" suggest="" that="" mirna-125b-5p="" and="" mirna-181b-5p="" may="" represent="" novel="" diagnostic="" biomarkers="" and="" that="" mirna-181b-5p="" may="" represent="" a="" therapeutic="" target="" for="" dkd(diabetic="" kidney="" disease).="" (translational="" research="">

Davolash o'simlikbuyrak kasalligi uchun:ajdaho o'tlar cistanche

Ⅰ& Ⅲ QISM UCHUN SHU YERGA BOSING

NATIJALAR

DKD sichqoncha modellarining buyraklarida miRNKlarni profillash(diabetik buyrak kasalligi).36 haftalik C57BL/6-Ins2Akit/J sichqonlari(AKITA sichqonlari) va 28 haftalik C57BLKS/J Tar- plus Leprh/ plus Leprb(db/db sichqonlar) buyraklarining mikroarray tahlili o‘tkazildi. Ellik turdagimiRNKlarjami 1881 tasi AKITA (n=4) va yoshga mos keladigan nazorat (n=4) sichqonlari (I-jadval, 1-rasm) buyraklarida statistik jihatdan muhim differentsial ifodani ko'rsatdi. Qo'shimcha ravishda, 87 turdagi ningmiRNKlardb/db (n=4) va yoshga mos keladigan nazorat (n=4) sichqonlarning buyraklarida statistik jihatdan ahamiyatli differentsial ifodani ko'rsatdi (jadval ⅡI va 2-rasm). Ulardan 15 turdagimiRNKlar(miRNA-20a-5p, miRNK-34a-5p,miRNA-125b-5p,miRNK-129-1-3p, miRNK-142a-3p,miRNK-129b-5p,miRNK-142a-5p, miRNK-146a-5p, miRNK-181b-5p,miRNA-342-3p,miRNA -455-5p, miRNA-223-3p,rmiRNA-652-3p, miRNK-6401 va miRNK-6980-5p) AKITA va JB da boshqaruv elementlaridan farqli ravishda ifodalangan /db sichqoncha. Bular orasida 15 tamiRNKlar, oltining ifodasimiRNKlar(ikkita yuqori tartibga solinganmiRNKlar(miRNK-34a-5p va miRNK-129b-1-3p) va to'rtta miRNK-142a-3p, (miRNK{{6} }}b-5p,miRNA-181b-5p va miRNK-223-3p)) qRT-PCR tahlili bilan tasdiqlangan (3-rasm).To‘qqiz boshqa miR-NA'lar qRT-PCR tahlili bilan statistik ahamiyatga ega o'zgarishlarni ko'rsatmadi.

3-rasm.Differentsial tarzda ifodalanganmiRNKlarqRT-PCR tahliliga ko'ra, AKITA va db / db sichqonlarining buyraklarida. qRT-PCR miRNK-34a-5p, miRNA-125b-5p, miRNK-129b- 1-3 ifodasini aniqlash uchun ishlatilgan. p, miRNK-142a-3p, miRNK{{10}}b-5p va miRNK-223a-3p har bir guruh (har bir guruh uchun n=6). Wilcoxon rank summasi testi. * P <>

Differensial ifodalangan miRNKlarning xarakteristikasi.Oltita ifoda darajalari differensial ifodalanganmiRNKlar(miRNA-34a-5p,-125b-5p,-129b-1-3p, -142a{{7} DKD buyraklarida }}p,-181b-5p va -223-3p)(diabetik buyrak kasalligi)sichqonlar buyrak kasalliklarining boshqa sichqoncha modellarining buyraklarida qRT-PCR yordamida o'lchandi: bir tomonlama siydik yo'llarining obstruktsiyasi natijasida hosil bo'lgan buyrak fibrozi modeli, o'tkir buyrak shikastlanishi modeli (ishemiya-reperfuzion shikastlanish), yoshga bog'liq buyrak kasalligi modeli (qarilik tezlashtirilgan sichqonlar) va immunoglobulin A nefropatiyasi modeli (HIGA/NscSlc sichqonlari). miRNK-125b-5p va miRNK-181b-5p ifoda darajalari sichqoncha modellari va tegishli boshqaruv sichqonlari orasida farq qilmadi (4-rasm), lekin qolgan to'rttasining ifoda darajalarimiRNKlar(miRNK-34a-5p,-129b-1-3p,-142a-3p va -223-3p) farqlanadi (4-rasm). Bu natijalar buyrakdagi miRNK-125b-5p va miRNK-181b-5p ning differensial ifodasi DKDga xos bo‘lishi mumkinligini ko‘rsatadi.(diabetik buyrak kasalligi).

4-rasm.TaqqoslashmiRNKturli xil buyrak kasalliklarida ifoda darajalari. miRNK{0}}a-5p, miRNK-125b-5p, miRNK-129b-1-3p, miRNK ifoda darajalari Buyrak kasalligining sichqoncha modellari buyraklarida -142a-3p, miRNK-181b-5p va miRNK-223-3p (n{{11} } har bir guruh uchun). Wilcoxon rank summasi testi. * P <0,05. qisqartmalar:="" samp,="" senescence-accelerated="" mouse="" prone;="" samr,="" senescence-tezlashtirilgan="" sichqonchaga="" chidamli;="" iri,="" ishemiya-reperfuziya="" shikastlanishi;="" uuo,="" bir="" tomonlama="" ureteral="" obstruktsiya;="" higa,="" yuqori="" immunoglobulin="" a;="" ns,="" muhim="">

Keyinchalik, biz ifoda darajalarini tahlil qildikmiRNKQRT-PCR tahlili yordamida vaqt o'tishi bilan AKITA sichqonlari va db/db sichqonlarining buyrak va zardobida -125b-5p va miRNK-181b-5p. DKD rivojlanishi bilan buyraklardagi miRNK-125b-5p ifoda darajalari pasaydi.(diabetik buyrak kasalligi)db/db sichqonchalari va AKITA sichqonlarida nazorat sichqonlari bilan solishtirganda (db/db sichqonlar {0}}.79±0.03-12 haftalik yoshida;P<0.05,0.59±0.03-fold at="" 28=""><0.01, akita="" mice:0.71±0.04-fold="" at="" 12=""><0.01, 0.16±0.03-fold="" at="" 36=""><0.05)(fig.5a).in contrast,="" the="" expression="" levels="" of="">miRNK{0}}b{1}}zardobdagi p 1,76±0 ga oshdi.11-katta(P)<0.05) in="" db/db="" mice="" at="" 28="" weeks-old;="" however,they="" did="" not="" change="" in="" akita="" mice="" (fig.5a).="" the="" expression="" levels="" of="" mirna-181b-5p="" in="" the="" kidney="" also="" decreased="" with="" the="" progression="" of="">(diabetik buyrak kasalligi)db/db sichqonchalar va AKITA sichqonlarida nazorat sichqonlari bilan solishtirganda (db/db sichqoncha {0}}.64±0.03-28 haftalikda; P< 0.05,="" akita="" mice:="" 0.75±0.05-fold="" at="" 12=""><0.05 and="" 0.38±0.07-fold="" at="" 36=""><0.05)(fig. 5b).additionally,="" the="" expression="" levels="" of="">miRNK{0}}b{1}}zardobdagi p 0.63±0.05-katta (P) gacha kamaydi.<0.05)in db/db="" mice="" at="" 28="" weeks-old;="" however,="" they="" did="" not="" show="" statistically="" significant="" changes="" in="" akita="" mice="">

5-rasm.AKITA va db/db sichqonlarining buyrak va qon zardobidagi miRNK{{0}}b-5p va miRNK-181b-5p darajalarining vaqt kursi tahlili . db/db va AKITA sichqonlarining buyraklaridagi miRNK-125b-5p darajalari (yuqori grafik) va sarum (pastki grafik) (har bir guruh uchun n=6) (a). db/db va AKITA sichqonlarining buyraklardagi miRNK-181b-5p darajalari (yuqori grafik) va sarum (pastki grafik) (har bir guruh uchun n=6) (b). Wilcoxon rank summasi testi. * P <>

In situ gibridizatsiya (ISH) tahlili shuni ko'rsatdiki, miRNK-125b-5p db/db sichqonlarning buyraklari glomeruli va tubulalarining yadrosi va sitozolida ifodalangan, ammo miRNK{{3} }}b-5p ni bu usul yordamida aniqlab bo'lmadi (6-rasm). Bu miRNK-125b-5p ning hamma joyda buyrakda ifodalanishini, ammo miRNK-181b-5p ning buyraklardagi ifodasi aniqlash uchun sezuvchanlik chegarasidan past ekanligini ko‘rsatishi mumkin. ISH tomonidan.

6-rasm.Db/db sichqonlarning buyraklardagi miRNK-181b-5p va miRNK-125b-5p uchun in situ gibridizatsiya tasvirlari. Db/db sichqonlarning buyraklarida miR-125b-5p ga antisens zond bilan duragaylash glomerulyar va quvurli hujayralar yadrosi va sitozolida ifodani aniqladi (qora donalar ijobiy signalni bildiradi), holbuki miR-181b-5p probiga gibridlanish amalga oshmadi. O'lchov paneli 50 mm. Qisqartmalar: RNU6, U6 Kichik yadroviy 1.

miRNK-125b-5p va miRNK-181b-5p ning DKDga ta'siri(diabetik buyrak kasalligi)in vivo.miRNK-125b-5p va miRNK-181b-5p ning ifodasi DKDda ayniqsa pasaytirildi.(diabetik buyrak kasalligi)(AKITA sichqonlari va db/db sichqonlari) va shuning uchun biz keyinchalik DKD uchun terapevtik maqsadlar sifatida ularning yaroqliligini tekshirish uchun db/db sichqonlarida miRNK-mimiklar yordamida har bir miRNKni haddan tashqari ifodalash ta'sirini aniqladik.(diabetik buyrak kasalligi). Db/db sichqonlarining buyraklariga miRNK-mimiklarni etkazib berish. Db/db sichqonlarining buyraklariga miRNK-mimiklarni etkazib berish uchun biz virusli bo'lmagan vektorlar bo'lgan polietilenimin nanozarrachalarini (PEI-NPs) ishlatdik. Etarlicha yetkazib berishni tasdiqlash uchunmiRNK-PEI-NPs yordamida mimikalar, PEI-NPs (miRNA-mimik-PEI-NPs) bilan konjugatsiyalangan Cy{2}}yorliqli miRNK-mimik dum venasi orqali db/db sichqonlarga tomir ichiga yuborildi. Cy3-yorliqli miRNK-mimik-PEI-NP'lar keyinchalik db/db sichqonlari buyraklarining glomerulyar va tubulointerstitial joylarida aniqlandi (7A-rasm).

7-rasm.Tarqalishi va ifoda darajalarimiRNKlarsichqon buyraklarida PEI-NP bilan boshqariladi. MiRNK-mimik (qizil) PEI-NPs bilan AOK qilingan va buyrakning tubulointerstitial hududida (yashil) va glomerulyar hududlarda kuzatilishi mumkin. Masshtab satri=200 mm. (A) miRNK-181b-5p-miRNK-181b-5p-mimic-PEI-NPs yordamida buyraklardagi miRNK-181b-5ekspressiyasi (har bir guruh uchun n=3) (B). Wilcoxon rank summasi testi. * P<0.05. abbreviations.="" dapi,="" 40="" ,6-diamidino-2-phenylindole;="" fitc,="" flfluorescein="" isothiocyanate;="" pei-nps,="" polyethylenimine="" nanoparticles.="" (color="" version="" of="" fifigure="" is="" available="">

miRNK{0}}b-5p haddan tashqari ifodalanishining DKDga ta'siri(diabetik buyrak kasalligi)in vivo.Yagona ma'muriyatimiRNK-181b-5p-mimic-PEI-NPs dumi venasi orqali bir hafta davomida saqlanib qolgan buyraklarda ikki baravar ortiq haddan tashqari ekspressiyaga olib keldi (7B-rasm). ning potentsial terapevtik ta'sirini o'rganishmiRNKDKDda -181b-5p(diabetik buyrak kasalligi), miRNK-181b-5p-mimik-PEI-NPs (3 nmol miRNK-mimik, N/P nisbati 6) 10 dan 20 haftagacha bo'lgan db/db sichqonlarga haftada bir marta tomir ichiga yuborilgan. yoshi. MiRNK-181b-5p-mimc-PEI-NPs qo‘llanilishi proteinuriyani (538±44 ug/mg kreatinin) nazorat qiluvchi db/db sichqonlarga qarshi (869±84 ug) sezilarli darajada kamaytirdi. /mg kreatinin) va db/db sichqonchani nazorat qilish -miRNK-PEI-NPs（965±152ug/mg kreatinin）20 haftalik (8A-rasm).miRNK-181b-5p-mimic-PEI-NPs shuningdek, db/db sichqonlarda DKDning xarakterli gistologik o'zgarishlarini, masalan, anormal glomerulyar kengayish va mezangial hududning kengayishini yaxshiladi (8B-rasm). bu db/db sichqonlarining buyraklarida kollagen I va kollagen IV ning ifoda darajasini ikki baravar kamaytirdi (Fig.8C va 8D). Bu topilmalar shuni ko'rsatadimiRNK-181b-5p-mimic-PEI-NPs DKD rivojlanishiga qarshi himoya ta'siriga ega.(diabetik buyrak kasalligi).

8-rasm.Boshqaruvning ta'sirimiRNKJB/db sichqonlarda -181b-5p-mimic-PEI-NP. Albominuriyaning o'zgarishi (har bir guruh uchun n=6). (A) Uilkoxon darajali yig'indisi testi. * P<0.05. histological="" evaluation="" of="" 20="" glomeruli="" per="" group="" (3-="" 4="" glomeruli="" per="" mouse="" and="" six="" mice="" per="" group).="" mesangial="" index="" was="" calculated="" using="" periodic="" acid-schiff="" (pas)-stained="" sections="" from="" the="" kidneys="" of="" normal="" mice="" (control),="" untreated="" db/db="" mice="" (db/db),="" db/db="" mice="" administered="">miRNK-181b-5p-mimic-PEI-NPs (db/db plyus)miRNK-181b-5p-PEI-NPs) va db/db sichqonlar nazorat-miRNA-PEI-NPs (db/db plyus nazorat-miRNK-PEI-NPs). Wilcoxon rank summasi testi. * P<0.05; y=""><0.05 compared="" with="" control="" (b).="" scale="" bar="50" mm.="" immunohistochemical="" and="" qrt-pcr="" evaluation="" of="" collagen="" i="" (c)="" and="" collagen="" iv="" (d)="" expression="" (n="6" per="" group).="" collagen="" i="" expression="" in="" glomerular="" and="" tubulointerstitial="" areas,="" evaluated="" using="" immunohistochemistry="" (upper="" panels)="" and="" col1a1="" mrna="" expression="" in="" the="" kidney,="" evaluated="" using="" real-time="" pcr="" (lower="" graphs)="" in="" each="" group.="" collagen="" iv="" expression="" in="" glomerular="" and="" tubulointerstitial="" areas,="" evaluated="" using="" immunohistochemistry="" (upper="" panels)="" and="" col4a1="" mrna="" expression="" in="" the="" kidney,="" evaluated="" using="" real-time="" pcr="" (lower="" graphs)="" in="" each="" group.="" wilcoxon="" rank="" sum="" test.="" *=""><0.05. scale="" bar="" 50="" mm.="" abbreviations:="" pei-nps,="" polyethylenimine="" nanoparticles;="" uacr,="" urine="" albumin-to-creatinine="">

miRNK-181b-5p-mimic-PEI-NPlarning DKDga ta'siri mexanizmi(diabetik buyrak kasalligi)in vivo.Har bir guruhdagi buyrak toʻqimalarida gen mikroarray tahlili oʻtkazildi: normal-mal sichqonlar (n=2), ishlov berilmagan db/db sichqonlar (n=2), miRNK yuborilgan db/db sichqonlar-181 b-5p-mimic-PEI-NPs (n=2) ​​va db/db sichqonlar nazorat ostidamiRNK-PEI-NPs (n=2). miRNA-181b-5p-mimic-PEI-NP administratsiyasi 24 genning ekspressiyasini oshirdi va maqsadli mRNK bo'lishi taxmin qilinayotgan Slc25a25 va Grm7 ni o'z ichiga olgan 27 genning ekspressiyasini kamaytirdi.miRNK-181b-5p ishlov berilmagan db/db sichqonlarga nisbatan to'rt baravar ko'proq (jadval Ⅲa va 9-rasm). Control-miRNA-PEI-NP administratsiyasi bir genning ekspressiyasini oshirdi va bir genning ekspressiyasini davolanmagan db/db sichqonlarga nisbatan to'rt baravardan ko'proq kamaytirdi (ma'lumotlar ko'rsatilmagan). Bundan tashqari, qRT-PCR (har bir guruh: n=6) yordamida mikroarray yordamida signalizatsiya yo'li tahlili ko'rsatdi.miRNK-181b-5p-mimic-PEI-NP administratsiyasi db/db dagi oltita signal yo‘lida yettita mRNK (Slc25a25, Gli3, Cryl, Erc2, Nrld, Creb313, Psme3) ifodalarini o‘zgartirdi. sichqonlar (10-rasm). Bu natijalar shundan dalolat beradimiRNK-181b-5p DKDga ta'sir qiladi(diabetik buyrak kasalligi)turli signal yo'llarini modulyatsiya qilish orqali.

9-rasm.Buyrakdagi differensial ifodalangan genlarning issiqlik xaritasi. Issiqlik xaritasi har bir guruhdagi sichqonlarning buyragidagi genlarning ierarxik klasterlashuvi va tizimli o'zgarishlarini ko'rsatadi (har bir guruhga n=2). Qisqartmalar: PEI-NPs, polietilenimin nanopartikullari.

miRNK-125b-5p ning DKDga ta'siri(diabetik buyrak kasalligi)in vivo. miRNK-125b-5p-mimic-PEI-NP db/db sichqonlarga miRNK-181b-5p-mimic-PEI-NPlar bilan bir xil usul yordamida yuborildi boshqaruv. Biroq, ma'muriyatmiRNK-125b-5p-mimic-PEI-NPs DKD rivojlanishiga ta'sir qilmadi(diabetik buyrak kasalligi)db/db sichqonlarda (Qo'shimcha materiallar). Bu natijalar shundan dalolat beradimiRNK-125b-5p DKD rivojlanishiga ta'sir qilmasligi mumkin(diabetik buyrak kasalligi).

10-rasm.ning haddan tashqari ko'payishi bilan mRNKdagi o'zgarishlarmiRNK-181b-5b. qRT-PCR tahlili (har bir guruh uchun n=6) ko'rsatdimiRNK-181b-5p-mimic-PEI-NP ma'muriyati har bir guruhda (n=6 ettita mRNK (Slc25a25, Gli3, Cry1, Erc2, Nr1d1, Creb3l3, Psme3) ifodasini o'zgartirdi har bir guruh uchun). Wilcoxon rank summasi testi. * P<>

miRNK-125b-5p va miRNK-181b-5p ning DKD diagnostik biomarkerlari sifatida muvofiqligi(diabetik buyrak kasalligi).DKD diagnostik biomarkerlari sifatida miRNK-125b-5p va miRNK-181b-5p ning foydaliligini tekshirish(diabetik buyrak kasalligi), har birining sarum darajalari DKD bilan og'rigan bemorlarda o'lchandi(diabetik buyrak kasalligi)(n=25), sog'lom sub'ektlar (n=25) va DKDdan tashqari buyrak kasalliklari bo'lgan mos keladigan bemorlar(diabetik buyrak kasalligi)(n=50) qRT-PCR yordamida. Har bir guruhning xarakteristikalari IV-jadvalda keltirilgan. Sarum darajasimiRNK{0}}b-5p sezilarli darajada yuqori (1,89±0.40-katta, P<0.05)and that="" of="" mirna-181b-5p="" was="" significantly="" lower="" ((0.30±0.06-fold,=""><0.05)in patients="" with="">(diabetik buyrak kasalligi)DKD dan boshqa buyrak kasalliklari bo'lganlar bilan solishtirganda (miRNK{0}}b-5p:(0.94±0.13-katta),miRNK{0}}b-5p:(1.{{10}}6±0.20-katta)) va sog'lom sub'ektlar (miRNK{{6) }}b-5p:(1.00±0.19-katlama), miRNK-181b-5p:(1.{{15} }±0.16-katlama))(11A-rasm). Bu ikki miRNK ham DKDni kamsitishga qodir edi(diabetik buyrak kasalligi)boshqa buyrak kasalliklaridan, qabul qiluvchining operatsion xarakteristikasi (ROC) tahliliga ko'ra [iRNA{{0}}b-5p: kesish qiymati 0,78,egri chiziq ostidagi maydon( AUC)0.74, sezgirlik 0.86, oʻziga xoslik 0.58, P<0.05; mirna-181b-5p:="" cut-off="" value="" 0.58,auc="" 0.79,sensitivity="" 0.93,="" specificity=""><0.05](fig.11b).the ratio="" of="" the="" serum="" levels="" of="" mirna-125b-5p="" and="">miRNK-181b-5p (miRNA-125b-5p/miRNA-181b-5p) DKD bilan og'rigan bemorlarda sezilarli darajada yuqori edi(diabetik buyrak kasalligi)(7,23±1.50-kat P<0.01)compared with="" patients="" with="" renal="" diseases="" other="" than="">(diabetik buyrak kasalligi)(1,78±0.28-katta) va sog'lom sub'ektlar (1,32±0.25-katta) (11C-rasm). Ushbu ifoda nisbatidan foydalanish DKDni farqlash uchun ushbu o'lchovlarning foydaliligini yaxshiladi(diabetik buyrak kasalligi)boshqa buyrak kasalliklaridan, ROC tahliliga ko'ra (miRNA{{0}}b-5p/miRNA-181b-5p: chegara qiymati 2.{{ 11}}5, sezgirlik 1.00, o‘ziga xoslik 0,73, AUC 0,92,P<>

11-rasm.DKD diagnostik biomarkerlari sifatida qon zardobidagi miR{0}}b-5p va miRNK-181b-5p darajalarining foydaliligi(diabetik buyrak kasalligi). Sog'lom odamlarda miR-125b-5p (chap panel) va miRNK-181b-5p (o'ng panel) sarum darajalari (n=25) , DKD bilan ishtirokchilar(diabetik buyrak kasalligi)(n=25) va DKDdan tashqari buyrak kasalliklari bo'lgan ishtirokchilar(diabetik buyrak kasalligi)(n=50) (A). DKD diagnostikasi uchun miRNK-125b-5p (chap panel) va miRNK-181b-5p (o'ng panel) zardobidagi darajalarining ROC tahlili(diabetik buyrak kasalligi)(B). Sarumdagi miRNK-125b-5p va miRNK-181b-5p (miRNK-125b-5p/miRNA) darajasining nisbati - 181b-5p) sog'lom sub'ektlarda (n=25), DKD bo'lgan ishtirokchilar(diabetik buyrak kasalligi)(n=25) va DKD (n=50) dan boshqa buyrak kasalliklari bo'lgan ishtirokchilar (chap panel); va miRNK-125b-5p va miRNK-181b-5p (miRNK-125b{{7}) ning sarum darajalari nisbatining ROC tahlili }p/miRNA-181b-5p) DKD tashxisi uchun(diabetik buyrak kasalligi)(o'ng panel) (C). Wilcoxon rank summasi testi. * P<0.05. abbreviations:="" dkd,="" diabetic="" kidney="">

Cistanche poyasining foydalari

Keyinchalik, miRNK-181b-5p va miRNK-125b-5p ning sarum darajalari va ularning DKD bilan og'rigan ishtirokchilarda ifodalanish nisbati.(diabetik buyrak kasalligi)(n=25) yoki DKDdan tashqari buyrak kasalliklari(diabetik buyrak kasalligi)qandli diabet bilan asoratlanganlar (n=25) solishtirildi. Bu ikki guruhning xarakteristikalari V-jadvalda keltirilgan. Garchi qon zardobidagi miRNK-125b-5p darajasi DKD bilan og'rigan bemorlarda pastroq bo'lgan bo'lsa-da(diabetik buyrak kasalligi)DKD dan tashqari buyrak kasalliklari bo'lganlarga qaraganda(diabetik buyrak kasalligi)diabetes mellitus bilan murakkablashgan, bu statistik ahamiyatga ega emas edi (Fig.12A). DKD bilan og'rigan bemorlarda qon zardobidagi miRNK-181b-5p darajasi sezilarli darajada past edi.(diabetik buyrak kasalligi)({0}}.37±0.08-katlama, P<0.05) compared="" with="" patients="" with="" kidney="" diseases="" other="" than="">(diabetik buyrak kasalligi)diabetes mellitus ({{0}}.94±0.24-katta) bilan murakkablashgan (12A-rasm). Sarumdagi miRNK-125b-5p va miRNK-181b-5p(miRNA-125b-5p/miRNA darajalarining nisbati -181b-5p) sezilarli darajada yuqori (6,65±1.57-katta,P<0.01) in="" patients="" with="">(diabetik buyrak kasalligi)DKD dan tashqari buyrak kasalliklari bo'lgan bemorlarga qaraganda(diabetik buyrak kasalligi)diabetes mellitus (2,13±0,51 marta) bilan murakkablashgan (12B-rasm). miRNA-125b-5p/miRNA-181b-5p DKD bilan og'rigan ishtirokchilarni sezilarli darajada kamsitdi(diabetik buyrak kasalligi)DKD dan tashqari buyrak kasalliklari bo'lganlardan(diabetik buyrak kasalligi)ROC tahliliga ko'ra qandli diabet bilan murakkablashgan (kesish qiymati 3.11, sezuvchanlik 0.77, o'ziga xoslik 0.91, AUC 0.84, P<0.05)(fig.12b).these findings="" suggest="" that="" the="" serum="" levels="" of="" mirna-125b-5p="" and="" mirna-181b-5p="" and="" their="" ratio="" may="" be="" useful="" diagnostic="" biomarkers="" of="">(diabetik buyrak kasalligi).

12-rasm.DKDni farqlash uchun qon zardobidagi miR{0}}b-5p va miRNK-181b-5p darajalarining foydaliligi(diabetik buyrak kasalligi)diabetes mellitus bilan asoratlangan boshqa buyrak kasalliklaridan. DKD bilan og'rigan ishtirokchilarda miR-125b-5p (chap panel) va miRNA- 181b-5p (o'ng panel) sarum darajalari(diabetik buyrak kasalligi)(n=25) va DKDdan tashqari buyrak kasalliklari bo'lgan ishtirokchilar(diabetik buyrak kasalligi)diabetes mellitus (n=25) (A) bilan asoratlangan. Sarumdagi miRNK-125b-5p va miRNK-181b-5p (miRNK-125b-5p/miRNA) darajasining nisbati DKD bo'lgan ishtirokchilarda -181b-5p).(diabetik buyrak kasalligi)(n=25) va DKD dan boshqa buyrak kasalliklari bo'lgan ishtirokchilar (n=25) (o'ng panel). Sarumdagi miRNK- 125b-5p va miRNK-181b-5p (miRNA-125b-5 darajasi nisbatining ROC tahlili DKD tashxisi uchun p/miRNA-181b-5p).(diabetik buyrak kasalligi)(chap panel) (B). Wilcoxon rank summasi testi. * p<0.05. abbreviations:="" dkd,="" diabetic="" kidney="">

Qisqartmalar:BMI= tana massasi indeksi; DAPI=4,6-diamidino-2-fenilindol; FITC=floresein izotiosiyanat; DKD= diabetik buyrak kasalligi; eGFR= taxminiy glomerulyar flotatsiya tezligi; HDL yuqori zichlikdagi lipoprotein; HIGA= yuqori immunoglobulin A; IRI= ishemiya-reperfuzion shikastlanish;LDL= past zichlikdagi lipoprotein; ns= muhim emas; PEI-NPs= polietilenimin nanozarralari;RNU6=U6 Kichik yadro 1; SAMP=qarilik tezlashtirilgan sichqoncha; SAMR{21}}qarilik tezlashtirilgan sichqonchani boshqarish; UACR= siydik albumin-kreatinin nisbati; UUO=bir tomonlama ureteral obstruktsiya

cistanche o'simligi

Eslatma: Xitoyning an'anaviy dorivor o'ti cistanche (shuningdek, "ajdaho o'ti" va "cho'l jenshen" deb nomlanadi) faqat qurg'oqchil va issiq cho'llarda o'sadi. To'qqizta o'lmas o'tlardan biri bo'lgan Cistanche (cistanche tubulosa/cistanche deserticola/desertliving cistanche/cistanche salsa) tarkibida echinacoside, acteosid, total feniletanoid glikozidlar, flavonoidlar, polisaxaridlar va boshqalar kabi samarali tarkibiy qismlar mavjud. odamlarning immuniteti, ichki a'zolari, miya hujayralari va neyronlari uchun oziqlantiruvchi o't va oziq-ovqat moddasi va boshqalar. Zamonaviy farmakologik tadqiqotlar sistanchening quyidagi ta'sirini tasdiqladi (sistanchening foydalari): immunitetni yaxshilash; jinsiy funktsiyani va buyrak faoliyatini yaxshilash; charchoqqa qarshi; qarishga qarshi; xotirani yaxshilash; anti-Parkinson kasalligi; Altsgeymer kasalligiga qarshi; antioksidant; yengillik - ich qotishi; yallig'lanishga qarshi; suyak o'sishini rag'batlantirish, terini oqartirish; jigarni himoya qilish; va boshqalar.

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