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系統(tǒng)性紅斑狼瘡疾病模型

疾病簡(jiǎn)介

系統(tǒng)性紅斑狼瘡(systemic lupus erythematosus,SLE)是一種復(fù)雜的慢性自身免疫性疾病,又被稱為“不死的癌癥”,表現(xiàn)為皮膚病變、關(guān)節(jié)炎、腎臟損害等癥狀。患者常伴有疲勞、發(fā)熱和體重下降等全身癥狀。

疾病模型

在 SLE 的研究中,動(dòng)物模型發(fā)揮著至關(guān)重要的作用。南模生物長(zhǎng)期致力于自身免疫性疾病相關(guān)研究,開發(fā)了多種 SLE 小鼠模型,分為自發(fā)性小鼠模型、誘導(dǎo)小鼠模型和人源化小鼠模型。

降植烷(pristane)是一種礦物油成分,它主要通過激活免疫系統(tǒng)中的B細(xì)胞來誘導(dǎo)SLE模型,疾病的發(fā)展過程更類似于人類SLE的慢性發(fā)病過程,但造模周期較長(zhǎng)。

咪喹莫特(Imiquimod, IMQ)主要通過激活TLR7來發(fā)揮作用,能快速啟動(dòng)免疫反應(yīng),發(fā)病相對(duì)較快,造模時(shí)間短,但其全身癥狀可能沒有Pristane誘導(dǎo)模型全面和嚴(yán)重。

基于上述原理,南模生物通過腎切+Pristane+IMQ誘導(dǎo)構(gòu)建了SLE模型,并且在不同品系(hCD3EDG/hCD19,BALB/c等)中進(jìn)行了表型驗(yàn)證,該模型發(fā)病快,大大縮短了造模時(shí)間,表型明顯,可用于SLE抗體類藥物的藥效評(píng)價(jià)。

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Fig.1 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Body weight. (B) Body weight change.?

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Fig.2?Serum anti-dsDNA IgG Ab of IMQ and Pristane induce nephrectomy Balb/c mice SLE model.

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Fig.3 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) mCD45+ cells in live cells proportion. (B) mCD20+ cells in live cells proportion. (C) mCD20+ cells in mCD45+ cells proportion.

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Fig.4 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Urine Albumin. (B) Urine Creatinine. (C) Albumin to creatinine ratio.

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Fig.5 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Spleen index. (B) Kidney index.?

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Fig.6 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Representative H&E staining. (B) Histopathology score.

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Fig.7 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) mIgG IHC staining. (B) % mIgG positive cells.

降植烷(pristane)是一種礦物油成分,它主要通過激活免疫系統(tǒng)中的B細(xì)胞來誘導(dǎo)SLE模型,疾病的發(fā)展過程更類似于人類SLE的慢性發(fā)病過程,但造模周期較長(zhǎng)。

咪喹莫特(Imiquimod, IMQ)主要通過激活TLR7來發(fā)揮作用,能快速啟動(dòng)免疫反應(yīng),發(fā)病相對(duì)較快,造模時(shí)間短,但其全身癥狀可能沒有Pristane誘導(dǎo)模型全面和嚴(yán)重。

基于上述原理,南模生物通過腎切+Pristane+IMQ誘導(dǎo)構(gòu)建了SLE模型,并且在不同品系(hCD3EDG/hCD19,BALB/c等)中進(jìn)行了表型驗(yàn)證,該模型發(fā)病快,大大縮短了造模時(shí)間,表型明顯,可用于SLE抗體類藥物的藥效評(píng)價(jià)。


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Fig.1 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Body weight. (B) Body weight change.?

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Fig.2 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Serum BUN. (B) Serum CRE. (*P<0.05, **P<0.01 Vs Group2)

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Fig.3 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Serum anti-dsDNA IgG Ab on Day 28. (B) Serum anti-dsDNA IgG Ab on Day 68.

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Fig.4 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) mCD45 cells in live cells proportion. (B) mCD20 cells in live cells proportion. (C) mCD20 cells in mCD45 cells proportion.

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Fig.5 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Urine Albumin. (B) Urine Creatinine. (C) Albumin to creatinine ratio. (*P<0.05,**P<0.01 Vs Group2)

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Fig.6 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Spleen photo and Kidney photo. (B) Spleen index and Kidney index.? (**P<0.01 Vs Group2)

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Fig.7 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model.?(A) Representative H&E images in SLE model. (B)Histopathology score. (*P<0.05 Vs Group2)

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Fig.9 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Representative IHC images in SLE model. (B) % mIgG positive cells.

人源化SLE模型是將SLE患者的人外周血單核細(xì)胞(PBMC)轉(zhuǎn)移到免疫缺陷小鼠中。該模型可幫助更好地理解人類SLE的特征,用于抗體,小分子等藥物的臨床前測(cè)試,加速轉(zhuǎn)化研究。

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Fig.1 The efficacy of Blinatumomab on SLE-PBMC induced SLE model in M-NSG mice. (A) Flow cytometry analysis on Day 7 , Day 14, Day21, Day28; (B) Elisa analysis on Day 7, Day 14, Day21, Day28; (C) Spleen index, kidney index.

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