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streptozotocin-induced diabetes C57BL/6J mouse

Streptozotocin destroys pancreatic beta cells, producing insulin deficiency, persistent hyperglycaemia and weight loss.

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

340 nm吸光度变化对应的葡萄糖浓度。

输出为达到既定高血糖阈值的成模动物;本方案不主张与某一原论文的给药操作等同,仅为可采用的诱导实现。

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。

实验动物

血液葡萄糖浓度酶法测定
组织
blood glucose assay samples
FFPE 肾组织 PAS 染色
性别
混合
组织
FFPE mouse kidney

实验步骤

Calibrate Cobas for Glucose analysis by running a multi analyte standard and two control serum. Calibrate Cobas for Glucose analysis by running a multi analyte standard and two control serum. Sample Handling as performed by the Cobas Mira Plus. Sample Handling as performed by the Cobas Mira Plus. a) Pipette 3 µL of sample into cuvette. b) Absorbance is measured at 340 nm. c) Add 100 µL of Glucose liquid reagent. d) Mixture is incubated at 37ºC for 10 minutes. e) Absorbance is measured at 340 nm. Change in absorbance is calculated.

Prepare the buffers and solutions as described below. Please note that the STZNa-Citrate solution should be prepared imm Prepare the buffers and solutions as described below. Please note that the STZNa-Citrate solution should be prepared immediately prior to injection so as to avoid degradation of the STZ. Mice should be fasted prior to injection; four hours is usually sufficient. Mice should be fasted prior to injection; four hours is usually sufficient. Place one mouse in the Isoflurane drop jar, according to your local IACUC anesthesia standards. Place one mouse in the Isoflurane drop jar, according to your local IACUC anesthesia standards. Remove mouse when breathing has slowed and animal is anesthetized Remove mouse when breathing has slowed and animal is anesthetized Inject appropriate amount of the STZ solution IP so the final dosage is **50 mg/kg mouse** Inject appropriate amount of the STZ solution IP so the final dosage is **50 mg/kg mouse** Allow mouse to awaken and place back in cage Allow mouse to awaken and place back in cage Repeat procedure for each animal; keep in mind that Isoflurane will need to be reloaded after every third or fourth anim Repeat procedure for each animal; keep in mind that Isoflurane will need to be reloaded after every third or fourth animal for proper anesthesia. Each mouse should be given one injection for 5 days consecutively. Each mouse should be given one injection for 5 days consecutively. Supply mice with 10% sucrose water, if necessary, to avoid sudden hypoglycemia post-injection. Supply mice with 10% sucrose water, if necessary, to avoid sudden hypoglycemia post-injection. **Mice should be tested for sufficient levels of hyperglycemia at 4 weeks postinjection. **If any of the experimental an **Mice should be tested for sufficient levels of hyperglycemia at 4 weeks postinjection. **If any of the experimental animals are not sufficiently diabetic, the low dose STZ protocol should be re-administered to those mice only at week 7 post injection to obtain proper levels of hyperglycemia.

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.

模型身份

模型名称
streptozotocin-induced diabetes C57BL/6J mouse
物种
mouse
品系
C57BL/6J

生物学特性

模型局限
Chemical induction; beta-cell loss depends on dose, route and strain, and the model does not reproduce the autoimmune or polygenic pathogenesis of human diabetes.

实验方法

实验方案

  • 血液葡萄糖浓度酶法测定

    以己糖激酶及葡萄糖-6-磷酸脱氢酶偶联反应测定葡萄糖,使用Cobas Mira Plus读取340 nm吸光度变化。

  • 小鼠低剂量链脲佐菌素多次注射糖尿病诱导

    柠檬酸钠缓冲液(pH 4.5)中现配 7.5 mg/ml 链脲佐菌素,禁食后异氟烷轻度麻醉下按 50 mg/kg 腹腔注射,连续 5 天,4 周后以高血糖水平判定成模。

  • 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。

配套试剂与材料

参考文献

  1. Mast Cells Regulate Wound Healing in Diabetes. Diabetes. 2016
  2. protocols.io · vv1 · John Stack; Gary Cline · This is an open access protocol distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
  3. Low-Dose Streptozotocin Induction Protocol (mouse), protocols.io v2
  4. 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
  5. ARRIVE 2.0 官方规范