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)。
Fig.1 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Body weight. (B) Body weight change.?
Fig.2?Serum anti-dsDNA IgG Ab of IMQ and Pristane induce nephrectomy Balb/c mice SLE model.
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.
Fig.4 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Urine Albumin. (B) Urine Creatinine. (C) Albumin to creatinine ratio.
Fig.5 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Spleen index. (B) Kidney index.?
Fig.6 IMQ and Pristane induce nephrectomy Balb/c mice SLE model. (A) Representative H&E staining. (B) Histopathology score.
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)。
Fig.1 IMQ and Pristane induce nephrectomy hCD3EDG/hCD19 mice SLE model. (A) Body weight. (B) Body weight change.?
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)
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.
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.
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)
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)
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)
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。
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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