系统性红斑狼疮疾病模型

疾病简介

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种复杂的慢性自身免疫性疾病,又被称为“不死的癌症”,表现为皮肤病变、关节炎、肾脏损害等症状。患者常伴有疲劳、发热和体重下降等全身症状。

疾病模型

在 SLE 的研究中,动物模型发挥着至关重要的作用。南模生物长期致力于自身免疫性疾病相关研究,开发了多种 SLE 小鼠模型,分为自发性小鼠模型、诱导小鼠模型和人源化小鼠模型。

降植烷(pristane)是一种矿物油成分,它主要通过激活免疫系统中的B细胞来诱导SLE模型,疾病的发展过程更类似于人类SLE的慢性发病过程,但造模周期较长。

咪喹莫特(Imiquimod, IMQ)主要通过激活TLR7来发挥作用,能快速启动免疫反应,发病相对较快,造模时间短,但其全身症状可能没有Pristane诱导模型全面和严重。

基于上述原理,南模生物通过肾切+Pristane+IMQ诱导构建了SLE模型,并且在不同品系(hCD3EDG/hCD19,BALB/c等)中进行了表型验证,该模型发病快,大大缩短了造模时间,表型明显,可用于SLE抗体类药物的药效评价。

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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)是一种矿物油成分,它主要通过激活免疫系统中的B细胞来诱导SLE模型,疾病的发展过程更类似于人类SLE的慢性发病过程,但造模周期较长。

咪喹莫特(Imiquimod, IMQ)主要通过激活TLR7来发挥作用,能快速启动免疫反应,发病相对较快,造模时间短,但其全身症状可能没有Pristane诱导模型全面和严重。

基于上述原理,南模生物通过肾切+Pristane+IMQ诱导构建了SLE模型,并且在不同品系(hCD3EDG/hCD19,BALB/c等)中进行了表型验证,该模型发病快,大大缩短了造模时间,表型明显,可用于SLE抗体类药物的药效评价。


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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模型是将SLE患者的人外周血单核细胞(PBMC)转移到免疫缺陷小鼠中。该模型可帮助更好地理解人类SLE的特征,用于抗体,小分子等药物的临床前测试,加速转化研究。

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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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