uninephrectomized db/db mouse (C57BLKS background)
db/db 纯合 leptin 受体突变合并单侧肾切除加速模型:蛋白尿与肾小管萎缩、间质纤维化提早出现,用于研究进展性糖尿病肾病。
研究设计
FFPE 肾组织切片的 PAS 染色流程,按源方案 FFPE 分支执行脱蜡、复水、氧化、Schiff 显色、苏木素复染、脱水透明和封片。具体切片厚度、视野与定量方法按研究设计确定。
结局指标
肾小球基底膜、系膜基质和糖蛋白呈 PAS 阳性(品红/紫红色),细胞核呈蓝色;按研究设计进行肾小球系膜扩张或病变范围判读。
输出为每样品尿白蛋白浓度(mg/l),按标准曲线插值报告;该读数本身不是白蛋白/肌酐比值,换算比值需另测尿肌酐。
实验动物
- 性别
- 混合
- 组织
- FFPE mouse kidney
- 性别
- 混合
- 组织
- mouse urine
实验步骤
Start with FFPE here: Allow PAS “kit” to come to room temperature on the bench. Start with FFPE here: For paraffin sections, deparaffinize in xylene, two changes, 00:03:00 each. Start with FFPE here: Hydrate through graded alcohols, 00:01:00 each: 100%, 100%, 95%, 70%, water Start with FFPE here: Rinse well in distilled water by holding finger over slides, pouring water into sink and adding water. Do this 5 times. Start Frozen samples here: Place in 0.5% Periodic acid for 00:10:00 (to oxidize). Start Frozen samples here: Rinse well in distilled water (follow Step 4). Start Frozen samples here: Pour Schiff’s reagent into Coplin jar containing slides. Allow to sit 15-30 minutes at room temperature (kidney samples ~30 minutes). Start Frozen samples here: Rinse in running warm (~40 °C) distilled or tap water (follow Step 4). The tissue should appear pink after rinsing with warm water. Start Frozen samples here: Place slides in movable gray slide holder. Start Frozen samples here: Counterstain in Hematoxylin (staining line) for 00:01:00. Start Frozen samples here: Rinse well in distilled water, starting with blue container next to hematoxylin (follow Step 4). Start Frozen samples here: Quickly dip slides into “Bluing” agent (0.5% ammonium hydroxide). Start Frozen samples here: Rinse 1 minute in distilled water until pink color is visible (follow Step 4). Start Frozen samples here: Dehydrate through graded alcohols, 10 short dips in each: 95%, 95%, 100%, 100% If the last 100% ethanol rinse is colored by residual stain, additional washing in new 100% ethanol solution should be performed. Start Frozen samples here: Fix in 2 rounds of xylenes, 00:01:00 each (in the hood). Start Frozen samples here: Coverslip slides: - Place coverslip on paper towel - Add 2-3 drops of cytoseal to edge (depending on size) - Dip slide into xylenes, take out and roll the xylene lengthwise on slide - Line up slide and cover slip and slowly place the slide on the coverslip - If needed, use dissecting tool to remove bubbles Start Frozen samples here: Image slides using a Leica brightfield scanner, AxioScan Z1 slide scanner (or equivalent) at 20x (~1 µm spatial resolution) and save as.tiff or.jpg file.
Prepare working reagent. Prepare working reagent. Prepare standards by serially diluting 200 mg/l standard 1:1 to make 100, 50, 25, 12.5, 6.25 standards. Prepare standards by serially diluting 200 mg/l standard 1:1 to make 100, 50, 25, 12.5, 6.25 standards. Add 25 μl of standard and sample to each well. Add 25 μl of standard and sample to each well. Add 125 μl of working reagent. Read in fluorimeter using 590 nm excitation and 616 nm emission. Add 125 μl of working reagent. Read in fluorimeter using 590 nm excitation and 616 nm emission. _**IMPORTANT: **__Make sure not to add any bubbles to the wells when dispensing reagents, this will interfere with reading in the platereader._ Use a polynomial 2nd order curve fit to construct a standard curve. Interpolate the values of the unknowns using the sta Use a polynomial 2nd order curve fit to construct a standard curve. Interpolate the values of the unknowns using the standard curve.
模型身份
- 模型名称
- uninephrectomized db/db mouse (C57BLKS background)
- 物种
- mouse
- 品系
- BKS.Cg-Dock7m +/+ Lepr^db
- 遗传背景
- C57BLKS
- 基因型/合子状态
- Lepr^db/Lepr^db
- 遗传修饰位点
- Lepr
- 等位基因
- Lepr^db
生物学特性
- 表型出现阶段
- UNX 后数周内进展;对照未手术 db/db 仅有早期病变。
- 适用研究问题
- 单侧肾切除加速 db/db 小鼠的糖尿病肾病进展(PAI-1 变异体治疗研究,尿白蛋白、肾功能与肾组织病理终点)。
- 模型局限
- 单侧肾切除是手术加速组分而非遗传背景;残余肾量本身改变血流动力学,不适用于两肾完整状态的推断;不主张本包之外的操作等同性。
实验方法
实验方案
- FFPE 肾组织 PAS 染色
本方案采用 protocols.io 人肾组织 PAS 染色 v3 的 FFPE 分支。石蜡切片经二甲苯脱蜡、梯度乙醇复水后,以高碘酸氧化、Schiff 试剂显色、苏木素复染,脱水透明并封片;用于显示肾小球基底膜、系膜基质及糖蛋白类物质。方案描述染色安排,不包含具体疾病模型的实验结果。
- 小鼠/大鼠尿白蛋白定量(Albumin Blue 580 染料结合微量板法)
用商品化 Albumin Blue 580 试剂在 96 孔微量板上以荧光读数定量小鼠或大鼠尿白蛋白浓度;含标准品系列稀释、加样、读数与标准曲线插值的完整流程。
配套试剂与材料
- Cytoseal 封片剂
封片
- Ethanol
梯度复水
- 组织学二甲苯(混合异构体)
脱蜡
- 苏木素染液
细胞核复染
- PAS 染色试剂盒(黏液染色,Abcam ab150680)
高碘酸氧化与 PAS 染色
- 大鼠血清白蛋白标准品(Sigma-Aldrich A6414)
标准曲线校准蛋白(大鼠血清白蛋白)
- Calibrator diluent for albumin quantification (Merck MilliporeSigma 09761)
标准品与样品稀释基质
- Albumin Blue 580 working reagent
显色/荧光结合试剂
- Albumin Blue 580 potassium salt solution (Merck MilliporeSigma 05497)
工作试剂组分
- Albumin assay buffer (Merck MilliporeSigma 79438)
工作试剂组分
参考文献
- A PAI-1 mutant retards diabetic nephropathy in db/db mice by protecting eNOS via reduced NOX1 (PMID 24443353)
- Animal Models of Kidney Disease: Challenges and Perspectives (early db/db with UNX row) (PMID 37526653)
- Elizabeth Neumann, Jamie Allen, Angela R.S. Kruse, Jennifer Harvey, Maya Brewer, Carrie Romer, Mark De Caestecker, Jeff Spraggins. PAS Staining of Fresh Frozen or Paraffin Embedded Human Kidney Tissue. protocols.io v3, 2023. https://doi.org/10.17504/protocols.io.x54v98nkzl3e/v3
- UC Davis (AMDCC) Urinary Albumin Excretion protocol, protocols.io v1
- Sigma-Aldrich A6414: Albumin from rat serum; biological source rat, UniProt P02770(核对日期2026-10-20)
- ARRIVE 2.0 官方规范