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CDAHFD 饮食诱导 NASH 模型(C57BL/6J 小鼠)

雄性 C57BL/6J 小鼠喂饲含 60 kcal% 脂肪、0.1% 甲硫氨酸的胆碱缺乏 L-氨基酸定义高脂饮食(CDAHFD)6 周后出现肝细胞脂肪变性、1–2 级小叶内炎症和 Masson 三色染色可检出的肝纤维化;肝羟脯氨酸含量及 Col1a1、Col3a1、Col4a1 mRNA 升高,α-SMA 蛋白表达增加。体重在最初 3 周可暂时下降,随后部分恢复。

Study design

石蜡包埋组织切片的天狼星红胶原染色。按源方案完成脱蜡水化、可选磷钨酸预处理、可选 Weigert 苏木素核染色、天狼星红/饱和苦味酸染色、乙酸分化、脱水透明与树脂封片;染色时间和分化程度按具体组织优化。样本来源、分组与切片数量按各研究设计确定。

Outcome measures

获得可供光学显微镜观察的 H&E 染色组织切片:细胞核蓝紫色、细胞质与结缔组织纤维粉红色,用于观察组织中细胞的整体结构与形态细节。本方案本身不产出病理评分数值,也不提供特定分子标志物的定量结果。

明场下胶原纤维呈红色,骨呈红色,肌肉、上皮和红细胞呈黄色,细胞核呈棕黑色;偏振光下胶原与骨呈双折射。结果用于胶原的定性或半定量观察;本方案不包含完整的纤维化面积、分期或 I/III 型胶原亚型定量。

Experimental animals

Hematoxylin and Eosin (H&E) staining for histopathology
Age
6 周 CDAHFD 喂养后
Sex
Male
Tissue
liver
Hematoxylin and Eosin (H&E) staining for histopathology
Age
6 周 CDAHFD 喂养后
Sex
Male
Tissue
liver
天狼星红(Picrosirius red)胶原染色
Age
6 周饮食
Sex
Male
Tissue
liver sections
天狼星红(Picrosirius red)胶原染色
Age
6 周饮食
Sex
Male
Tissue
liver sections
Hematoxylin and Eosin (H&E) staining for histopathology
Age
1-24 周龄(PMID:23305254)
Sex
Male
Tissue
liver

Experimental procedures

脱蜡(Dewaxing) 石蜡切片置于二甲苯中脱蜡 3 次,每次 00:03:00。 复水(Rehydration) 石蜡切片依次置于 100% 乙醇中 3 次、每次 00:03:00,再置于 95% 乙醇中 1 次、00:03:00,随后用水漂洗。 苏木素核染色(Hematoxylin staining) 石蜡切片以苏木素染液染色 00:00:20,随后在流水下冲洗 00:01:00。 分化与返蓝(Differentiation and bluing) 石蜡切片置于返蓝液中 00:01:00,随后在流水下冲洗 00:01:00;此步使细胞核呈现蓝色。 伊红染色(Eosin staining) 石蜡切片以伊红复染 00:00:10;此步使细胞质成分与结缔组织纤维呈现粉红色。 脱水与透明(Dehydration and Clearing) 石蜡切片依次置于 95% 乙醇中 00:02:00、100% 乙醇中 2 次、每次 00:02:00,随后置于二甲苯中 2 次、每次 00:02:00。 封片(Mounting) 石蜡切片以 Permount 封片介质加盖玻片封固。

脱蜡与水化 Dewax and rehydrate tissue sections 磷钨酸预处理 Incubate in 0.2% phosphotungstic acid (PTA) solution PTA solution: 0.2 g PTA in 100 ml distilled water Phosphotungstic acid hydrate Merck MilliporeSigma (Sigma-Aldrich) Catalog #P4006 This PTA pre-treatment prevents non-specific nuclear staining in PSR, thereby enhancing the distinction between collagen and cellular staining. Elimination of the non-specific staining is particularly beneficial if performing automated digital image analysis, improving rigour of the method. 磷钨酸预处理 Rinse with distilled water 磷钨酸预处理 Rinse with distilled water 磷钨酸预处理 Rinse with distilled water 核染色 Stain in Weigert’s Haematoxylin (combine solution A & B immediately before use) Solution A: 1 g Haematoxylin in 100 ml of 95% Ethanol Solution B: 1.6 g Ferric chloride hexahydrate (Iron III chloride; FeCl3.6H2O) + 95 ml distilled water + 1 ml concentrated HCl Haematoxylin Fronine Laboratory Supplies Catalog #JL555S Ethanol Hurst Scientific Catalog #EIMS95-5L Iron (III) chloride hexahydrate Merck MilliporeSigma (Sigma-Aldrich) Catalog #F2877 Hydrochloric Acid Banksia Scientific Company (AJAX FineChem) Catalog #AJA256 核染色 Wash with running tap water to remove excess stain 核染色 Differentiate with acid alcohol (5-10 dips) to clear the slides [1% Hydrochloric Acid (HCl) in 70% Ethanol] Hydrochloric Acid Banksia Scientific Company (AJAX FineChem) Catalog #AJA256 Ethanol POCD Scientific Catalog #ETHABS70WV5 核染色 Wash with running tap water It is important to ensure that the slide is completely cleared of excess Weigert's Haematoxylin at this point. If there is carryover into the PSR solution, it becomes contaminated with the ferric chloride, resulting in non-specific red background staining. 胶原染色 Stain with picrosirius red solution Solution: 0.1 g Sirius Red F3BA + 100 ml saturated aqueous picric acid 1.3 Mass Percent, in distilled water Sirius red F3BA BDH Chemicals Ltd Poole England Catalog #34149 CI: 35780 Picric acid May & Baker LTD Sirius red is also known as "Direct Red 80" Solution can be re-used many times. Lasts 20 years. Picric acid is an unstable explosive when dry, where it becomes highly sensitive to shock, heat and friction. Ensure it remains hydrated at all times. Picric acid reacts with metals to form unstable picrate salts which are more explosive. Do not use metal containers, lids or racks. Picric acid is toxic if swallowed, inhaled or absorbed through the skin. Consult the MSDS and follow all recommended safety precautions. 天狼星红分化 Differentiate the PSR staining with 2 changes of a 0.5% acetic acid solution, 5-10 dips each. The timing of this differentiation (or number of dips) should be optimised for each specific tissue. Use a microscope to check that collagen is stained red and cells are stained yellow. Solution: 0.5 ml glacial acetic acid + 99.5 ml distilled water Glacial acetic acid Ajax Finechem (ThermoFisher Scientific) Catalog #AJA1-500ML 天狼星红分化 Drain acetic acid solution from the slides as much as possible 脱水、透明与封片 100% ethanol Note: If you want to maintain the yellow cytoplasmic staining, ensure the dehydration is quick. 10 dips per ethanol step is usually sufficient. Ethanol POCD Scientific Catalog #ETHABS20M 脱水、透明与封片 100% ethanol Ethanol POCD Scientific Catalog #ETHABS20M 脱水、透明与封片 100% ethanol Note: ensure whole slide and slide rack is fully immersed in ethanol to remove all traces of water, preventing water contamination of the xylene Ethanol POCD Scientific Catalog #ETHABS20M 脱水、透明与封片 100% Xylene Xylene POCD Scientific Catalog #XYL5P 脱水、透明与封片 100% Xylene Xylene POCD Scientific Catalog #XYL5P 脱水、透明与封片 Coverslip with a resinous mounting medium, such as DPX DPX Mountant for histology Merck MilliporeSigma (Sigma-Aldrich) Catalog #06522 结果 Collagen: Red Bone: Red Muscle: Yellow Epithelium: Yellow Erythrocytes: Yellow Nuclei: Brown - Black Note - collagen and bone stained specifically with Sirius Red are birefringent, enabling identification and quantification under polarised light microscopy. [GAA_no W 10x 2.jpeg]]( [GAA_no W 10x 2_Pol.jpeg]]( [GAA_W 20x.jpeg]]( [GAA_W 20x_Pol.jpeg]](

Model identity

Model name
CDAHFD 饮食诱导 NASH 模型(C57BL/6J 小鼠)
Species
mouse
Strain
C57BL/6J
Genetic background
C57BL/6J 近交系;NASH 由胆碱缺乏、L-氨基酸定义的高脂饮食诱导,非基因改造。

Biological characteristics

Phenotype stage
6 周龄雄性小鼠起始喂饲;6 周时已出现纤维化,14 周观察体重时程。
Research questions
饮食成分如何在不依赖显著肥胖的情况下驱动 NASH 的脂肪变性、炎症与纤维化;不同小鼠品系对 CDAHFD 的纤维化易感性差异。
Limitations
该模型依赖特定胆碱/甲硫氨酸缺乏配方,不能代表人类代谢功能障碍相关脂肪性肝病的全部病因;A/J 小鼠在同方案下未形成纤维化,说明品系背景影响外推;6 周纤维化资料来自单一雄性队列,不能据此设定所有实验的病程阈值。

Experimental methods

Experimental protocols

  • Hematoxylin and Eosin (H&E) staining for histopathology

    Hematoxylin and eosin (H&E) staining of fixed, paraffin-embedded tissue sections (4 μm). The workflow covers dewaxing, rehydration, hematoxylin nuclear staining, bluing, eosin counterstaining, dehydration and clearing, and coverslipping, yielding blue-purple nuclei and pink cytoplasm and connective tissue fibers for light-microscopic assessment of cellular and tissue morphology.

  • Hematoxylin and Eosin (H&E) staining for histopathology

    Hematoxylin and eosin (H&E) staining of fixed, paraffin-embedded tissue sections (4 μm). The workflow covers dewaxing, rehydration, hematoxylin nuclear staining, bluing, eosin counterstaining, dehydration and clearing, and coverslipping, yielding blue-purple nuclei and pink cytoplasm and connective tissue fibers for light-microscopic assessment of cellular and tissue morphology.

  • 天狼星红(Picrosirius red)胶原染色

    This protocol adopts the protocols.io Picrosirius red staining for histology v1. Formalin-fixed paraffin-embedded sections are dewaxed and rehydrated, optionally pre-treated with phosphotungstic acid and counterstained with Weigert haematoxylin, then stained with 0.1% Sirius Red F3BA in saturated picric acid, differentiated with acetic acid, dehydrated, cleared and mounted. Collagen appears red in bright field and birefringent under polarised light. The record describes staining and microscopic observation, not a complete fibrosis area or stage quantification.

  • 天狼星红(Picrosirius red)胶原染色

    This protocol adopts the protocols.io Picrosirius red staining for histology v1. Formalin-fixed paraffin-embedded sections are dewaxed and rehydrated, optionally pre-treated with phosphotungstic acid and counterstained with Weigert haematoxylin, then stained with 0.1% Sirius Red F3BA in saturated picric acid, differentiated with acetic acid, dehydrated, cleared and mounted. Collagen appears red in bright field and birefringent under polarised light. The record describes staining and microscopic observation, not a complete fibrosis area or stage quantification.

  • Hematoxylin and Eosin (H&E) staining for histopathology

    Hematoxylin and eosin (H&E) staining of fixed, paraffin-embedded tissue sections (4 μm). The workflow covers dewaxing, rehydration, hematoxylin nuclear staining, bluing, eosin counterstaining, dehydration and clearing, and coverslipping, yielding blue-purple nuclei and pink cytoplasm and connective tissue fibers for light-microscopic assessment of cellular and tissue morphology.

Reagents and materials

References

  1. An improved mouse model that rapidly develops fibrosis in non-alcoholic steatohepatitis. International Journal of Experimental Pathology (2013), PMID 23305254.
  2. Animal Models of Nonalcoholic Fatty Liver Disease—A Starter's Guide (2017), PMID 28953222.
  3. Nathalia L. Oliveira; Samantha Gruenheid. Hematoxylin and Eosin (H&E) staining for histopathology. protocols.io, v1, 2026-07-31. DOI: 10.17504/protocols.io.kxygxr9jdg8j
  4. Epredia Signature Series Hematoxylin (7221), 产品信息页, Fisher Scientific
  5. Epredia Signature Series Bluing Reagent (7301), 产品信息页, Fisher Scientific
  6. Epredia Signature Series Eosin Y (7111), 产品信息页, Fisher Scientific
  7. Xylene, Fisherbrand HistoPrep (HC7001GAL), 产品信息页, Fisher Scientific
  8. Fisher Chemical Permount Mounting Medium (SP15 产品族), 产品信息页, Fisher Scientific
  9. Ethanol (CID 702, CAS 64-17-5), PubChem 化合物标准记录
  10. Samson Dowland. Picrosirius red staining for histology. protocols.io. https://doi.org/10.17504/protocols.io.ewov11oxpvr2/v1
  11. López De Padilla CM, Coenen MJ, Tovar A, De la Vega RE, Evans CH, Müller SA. Picrosirius Red Staining: Revisiting Its Application to the Qualitative and Quantitative Assessment of Collagen Type I and Type III in Tendon. J Histochem Cytochem 2021;69(10):633-643. PMID 34549650. doi:10.1369/00221554211046777
  12. ARRIVE 2.0 guidelines