Cistanche Desertikolaning neyroendokrin-immun funktsiyasini va uning guruch sharobini bug'da pishirish mahsulotlarini glyukokortikoid bilan induktsiyalangan kalamush modelida o'rganish-Ⅱ

3.2.4. Immunogistokimyo

Neyronal apoptoz ko'plab apoptoz va antiapoptotik genlar, asosan apoptozni rag'batlantiruvchi Bax gen va Bcl-2 genlar oilasining antiapoptotik genlari tomonidan boshqariladi. Bcl-2 mitoxondriya, endoplazmatik retikulum va yadro membranalari kabi reaktiv kislorod ishlab chiqaruvchi organellalarda joylashgan. Bcl-2 kislorodli erkin radikallarga kam ta'sir qiladi, ammo ta'sir qilishi mumkinhujayralardagi oksidlovchi shikastlanishning oldini oladi. Bax sitoplazmadan mitoxondriyal membranaga o'tadi, mitoxondriyal membrana tuzilishini o'zgartiradi va sitoxrom c ning chiqarilishiga va apoptozning induksiyasiga yordam beradi.

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Buyrak usti bezi sitoplazmasida Bax va Bcl{0}} oqsilining ifodasi bor edi. Bo'yash barcha sariq zarralarni ko'rsatdi. BC guruhi bilan solishtirganda, MC guruhidagi Bax oqsilining o'rtacha optik zichligi sezilarli darajada oshdi (P).< 0.01). Compared to that of the MC group, the average optical density in the CD-LD and WCD-LD groups decreased significantly (P < 0.01) (Figure 5(a)).

Shakl 5(b) BC guruhi bilan solishtirganda, MC guruhidagi Bcl-2 oqsilining o'rtacha optik zichligi sezilarli darajada kamaydi (P)< 0.05). Compared to that of the MC group, the average optical density in the WCD-HD and CD-HD groups increased significantly (P < 0.01), while those of the WCD-MD and CD-MD groups increased (P < 0.05).

Kaspaza{0}} oqsili asosan sitoplazmada normal to'qimalarda o'zining asl shaklida joylashadi va kam ifodalanadi. Ijobiy signallar och sariq yoki jigarrang sariqdir. BC guruhi bilan solishtirganda, MC guruhidagi kaspaza-3 ifodasi sezilarli darajada oshdi (P< 0.05). Compared to that of the MC group, the expression of caspase-3 in the WCD-HD and WCD-MD groups increased (P < 0.05) (Figure 5(c)).

Oddiy to'qimalarda Fas genining ifodasi kamaydi va in situ gibridizatsiya uchun ijobiy signal jigarrang sariq edi. Shakl 5 (d) da ko'rsatilganidek, BC guruhiga nisbatan, MC guruhidagi Fas oqsilining o'rtacha optik zichligi oshdi (P).< 0.05). Compared to that of the MC group, the average optical density in the WCD-HD and WCD-LD groups improved (P < 0.05) (Figure 5(d)).

FasL oqsili asosan hujayra membranasi yoki sitoplazmasida joylashgan bo'lib, uning ijobiy signallari jigarrang rangga ega. BC guruhi bilan solishtirganda, MC guruhidagi FasL genining o'rtacha optik zichligi sezilarli darajada oshdi (P).< 0.05). Compared to that of the MC group, the average optical density of the FasL gene in the WCD-HD, WCD-MD, CDHD, and CD-MD groups increased significantly (P < 0.01) (Figure 5(e)).

Natijalar shuni ko'rsatdiki, CD va WCD mumkinyallig'lanish hujayralarida apoptozni keltirib chiqaradiva FasL oqsilining ifodalanishi va Fas oqsili bilan bog'lanishi, kaspaza{0}} oqsilini faollashtirish va kaspaz kaskadini ishga tushirish orqali buyrak usti bezlari shikastlanishini kamaytiradi. WCD-HD guruhining ta'siri eng yaxshi edi.

3.3. Immun funktsiyasini aniqlash

3.3.1. Immun organ indeksi

BC guruhidagilarga nisbatan timus koeffitsienti va MC guruhining taloq indeksi sezilarli darajada kamaydi (P).< 0.01). Compared to the MC group, the WCD-MD group had the greatest difference (P < 0.05). The thymus coefficient was almost back to the normal level. For the spleen index, the WCDMD, WCD-LD, and CD-MD groups showed significant differences compared with that of the MC group (P < 0.01) (see Figure 6). Therefore, WCD and CD treatment could protect the immune organs, and the effects of WCD were better.

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3.3.2. Periferik qonda T-limfotsitlar quyi to'plamlarini aniqlash

Miloddan avvalgi va har bir dori guruhidagi yuqori chap kvadrantdagi CD4+ hujayralar va o'ng pastki kvadrantdagi CD8+ hujayralari ulushi MC guruhidagiga qaraganda yuqori edi. BC guruhi bilan solishtirganda, CD4+ThCD8+ nisbati MC guruhida sezilarli darajada kamaydi (P).< 0.01). Compared to that of the MC group, the ratio of CD4+ThCD8+ increased significantly in the PC group, the WCD group, and the CD-HD group (P < 0.01) (Figure 7).

3.3.3. Sarumdagi IL-10, IL-6, IL-2, TNF-A va IFN-C darajasini aniqlash

8-rasm BC guruhiga nisbatan IL-6, TNF- va IFN-c darajasi sezilarli darajada oshganligini ko'rsatadi (P).< 0.01). The level of IL-10 and IL-2 decreased in the MC group. Compared to that of the MC group, the level of IL-6, TNF-α, and IFN-c decreased and IL-10 and IL-2 increased in serum in each of the drug groups. The effect of WCD was better than the effect of CD, especially in the WCD-MD group, in which the effect was close to that of the PC group.

3.3.4. Limus to'qimalarining mikroskopini kuzatish tajribasi natijalari

9-rasmda miloddan avvalgi guruhda ko'p miqdorda limfotsitlar mavjudligi ko'rsatilgan. Limfotsitlar va retikulotsitlar markazda yumaloq yoki ovalsimon tarqoq timositlar bilan erkin joylashadi. Nekroz, yallig'lanish hujayralarining infiltratsiyasi va g'ayritabiiy o'zgarishlar yo'q edi.

MC guruhi markazda limfotsitlar va retikulotsitlarning tartibsiz joylashuvi bilan ko'p miqdorda limfoid nekroz to'qimasini ko'rsatdi. Dumaloq yoki oval timotsitlar g'oyib bo'ldi, massiv hujayra degeneratsiyasi yoki nekrozi aniq bo'ldi va anormal patologik o'zgarishlar bilan yallig'lanish hujayralari infiltratsiyasi mavjud.

CD guruhlarida limfotsitlarning morfologik xususiyatlari normal holatga qaytdi, markaziy limfotsitlar va retikulotsitlarning joylashishi deyarli normal edi. Dumaloq yoki oval shaklidagi timositlar tiklangan, ammo oz sonli degenerativ yoki nekrotik limfotsitlar va infiltratsiya qiluvchi yallig'lanish hujayralari qolgan.

WCD guruhlari va PC guruhida limfotsitlarning morfologik xususiyatlari yaxshiroq tuzatildi. Markazdagi limfotsitlar va retikulotsitlar yaxshi moslashgan, yumaloq yoki oval timotsitlar deyarli normal edi, lekin oz miqdorda infiltratsiya qiluvchi va degenerativ limfotsitlar qoldi.

3.4. CaM protein genining ifodasi

RQ qiymati (CaM mRNA -aktin mRNK) CaM mRNK ifodasini tekshirish uchun ko'rib chiqildi. BC guruhining RQ 1. MC guruhida gipotalamusda CaM mRNKning ifodasi sezilarli darajada oshdi (P).< 0.01), while the value decreased in the WCD-HD, WCD-MD, WCDLD, and CD-HD groups (P < 0.05) (Figure 10). The expression of CaM mRNA in the hypophysis in the MC group was lower than that in the BC group (P < 0.01). The expression in the WCD-HD, WCD-MD, WCD-LD, CD-HD, and CD-LD groups increased (P < 0.05), and the effect in the WCD groups was better than the effect in the CD groups.

4. Munozara

Xitoy farmakopeyasi [2] CD va WCD dan klinikada dekok bo'laklarining asosiy turlari sifatida foydalanish mumkinligini qayd etadi. Guruchli sharob bilan bug'langandan so'ng,qarishga qarshi va tonifikatsiya qiluvchi buyrak-yang ta'sirikuchaytirildi. UPLC-QqQ-MS orqali biz guruch sharobini bug'lash jarayonida kimyoviy material bazasidagi miqdoriy o'zgarishlarni aniqladik. Iridoid glikozidlar beqaror edi va bu glikozidlarning tarkibi kamaydi, hatto aniqlanmaydi. Feniletanol glikozidlarining tarkibi ham o'zgargan, bu farmakodinamikada va klinik ta'sirda o'zgarishlarga olib kelishi mumkin.

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Klassik buyrak-yang etishmovchiligi modeli kortikosteronni teri ostiga yuborish orqali takrorlandi [19]. Kortikosteronning haddan tashqari dozasi gipotalamusdagi CRH sirini inhibe qilishi mumkin. Shu bilan birga, ACTH siri ham inhibe qilindi. Buyrak usti bezlari korteks gormoni darajasi pasaygan, shuning uchun HPA o'qi funktsiyasi pasaygan. HPA o'qining gipofunktsiyasi buyrak-yang etishmovchiligining umumiy xususiyatidir [20]. Keyin kalamushlar "tushish" hodisalarini ko'rsatadi va alomatlar klinikada buyrak-yang etishmovchiligi belgilariga mos keladi.

MC guruhida kalamush zardobida CRH, ACTH, T va CORT darajasi sezilarli darajada kamaydi (P).< 0.01). After being treated by CD and WCD, the content of CRH, ACTH, T, CORT, and cortisol all increased to some degree, and the effect of WCD-MD was the best, almost equal to that in the PC group. These results indicated that the relative hormone balance in the HPA axis had been destroyed in the MC group, CD and WCD could improve the functional recovery of abnormal adrenal axis hormone levels, but the effect of WCD was better.

Bcl-2 oila a'zolarining nisbatini modulyatsiya qilish FasThFasL o'lim retseptorlari yo'lida vositachilik qiladigan asosiy mexanizmlardan biridir va Bcl{1}} oilasi mitoxondriyal yo'lni tartibga soladi [21]. Apoptozni inhibe qiluvchi omil Bcl-2 va apoptozni qo'zg'atuvchi omillar, masalan, Bax, Bcl-2 oilasiga tegishli [22]. Hujayra apoptozi apoptozni inhibe qiluvchi omillar va apoptozni qo'zg'atuvchi omillarning nisbiy nisbati bilan aniqlanishi mumkin [23]. Mitoxondriyalar apoptozning ko'p shakllari uchun markaziy nazorat punktlari vazifasini bajaradi [24]. Ushbu tadqiqot shuni ko'rsatdiki, CD-MD va WCDlar Bax ifodasini chiqarib, Bcl-2 ni oshirishi mumkin.buyrak-yang etishmovchiligini yaxshilash. Fas Fas ligand (FasL) bilan bog'lanish orqali apoptozni qo'zg'atuvchi asosiy o'lim retseptoridir [25]. MC guruhida Fas va FasL ifodasi oshdi, WCD-MD guruhida esa bu ifoda sezilarli darajada oshdi (P).< 0.01) compared with the MC group. Both FasThFasL and BaxThBcl-2 systems transduce apoptotic signals to the caspase family [26]. Caspase-3 is one of the pivotal proteinases that initiate cell apoptosis. The activation of caspase-3 indicates that apoptosis enters an irreversible stage [27]. The expression of caspase-3 in the MC group increased and increased significantly in the WCD-HD and WCD-MD groups (P < 0.05).

Immun funktsiyasining etishmasligi buyrak-yang etishmovchiligining muhim ko'rinishlaridan biridir [28]. Ushbu tadqiqotda biz WCD-MD guruhidagi taloq va timus indeksi sezilarli darajada tiklanganini aniqladik (P.< 0.01, P < 0.05). The immune response of the immune system is regulated mainly by the Th subgroups [29]. IL-2 is the growth factor for T cells, secreted by T cells and macrophages, participates in inflammatory regulation, regulates immunity, and increases infection resistance [30]. The level of IL-2 in the MC group decreased (P < 0.01), and after treatment with CD and WCD, the level of IL-2 recovered. IL-6 and TNF-α are proinflammatory cytokines. Increased levels of IL-6 and TNF-α cytokines cause cytokine imbalances and exacerbate inflammation. The levels of IL-6 and TNF-α increased in the MC group, while after treatment, the levels of IL-6 and TNF-α decreased. T cells are divided into CD4 cells and CD8 cells, and the CD4+ThCD8+ ratio can be used as an important index of immune regulation [31]. CD4+ThCD8+ in the MC group decreased (P < 0.01), while in the WCD and CDHD groups increased (P < 0.01).

HPA o'qi eng muhim tartibga soluvchi tizimdir, chunki u glyukokortikoid sekretsiyasini va buyrak usti bezlari po'stlog'ining sekretor funktsiyasini saqlab turish uchun endokrin tizimni tartibga soladi [32]. Gipotalamus to'qimasida CaM mRNKning haddan tashqari ko'payishi buyrak yangining etishmovchiligi bilan bog'liq edi. CD va WCD kaltsiy kanallarini to'sib qo'yishi, gipotalamusdagi CaM mRNK ifodasini inhibe qilishi va kaltsiy oqimini kamaytirishi, shu bilan Ca2+·CaM kompleks faolligini kamaytirishi mumkin.

Buyrak-yang etishmovchiligining shakllanishi surunkali kasallikning rivojlanish jarayonidir. Buyrak endi sof anatomik tushuncha emas va u neyroendokrin-immunitet va genitouriya tizimlari uchun umumiy atamadir. Neyroendokrin-immun (NEI) tarmog'i muhim integratsiyalashgan tartibga solish tizimidir [33]. CD va WCD HPAT o'qi funktsiyasini tartibga solishi va buyrak-yang etishmovchiligini tiklashni yaxshilashi mumkin. Bu natija buyrak-yang etishmovchiligining klinik profilaktikasi va davolash uchun eksperimental asos bo'lib xizmat qiladi.