• Modeling Mechanism：

  Tyloxapol, as a nonionic surfactant, has the following core modeling mechanism: ① It specifically inhibits lipoprotein lipase (LPL) activity, blocking the hydrolytic metabolism of triglycerides (TG) in plasma, especially inhibiting the breakdown of very low-density lipoprotein (VLDL)-TG, leading to rapid accumulation of TG in the blood; ② It interferes with the hepatic VLDL secretion regulation pathway, reducing the transport and clearance of TG to peripheral tissues, further exacerbating the increase in plasma lipids; ③ Short-term administration can induce acute hyperlipidemia, simulating the pathological state related to clinical lipid metabolism disorders, and is suitable for evaluating the intervention effect of drugs on lipid clearance and lipoprotein metabolism.

• Related Products：

  Tyloxapol (T0307)

• Modeling Method：

  Experimental Subject：

  Mice, C57BL/6 mice (or Apoe⁻/⁻ mice to enhance model stability), Male, weighing 20–25 g

  Dosage and Administration Route：

  ① Core modelling:
  - Tyloxapol, 500 mg/kg, dissolved in physiological saline, intravenous tail injection, single dose;
  ② Control treatment:
  - Blank control: tail vein injection of equal volume saline;
  - Model validation group: Optionally pre-treat with high-fat diet (HFD, 60% kcal from fat) for 2 weeks followed by Tyloxapol injection to establish a "diet+drug" dual-induced model;
  Chronic model (optional): Weekly injections for 4 consecutive weeks to induce persistent hyperlipidaemia.

  Dosing Frequency and Duration Model：

  Single Dose

• Validation：

  1. Lipid Indicators (Core Validation): - Plasma TG: 8 hours after injection, TG levels increased 3-5 times compared to the control group (P<0.01), and remained high for 24 hours; - Lipoprotein Profile: FPLC analysis showed a significant increase in VLDL-TG peak (more than 400% higher than the control group), a slight increase in low-density lipoprotein (LDL) cholesterol, and no significant change in high-density lipoprotein (HDL) cholesterol; - Liver Lipids: Hepatic TG content did not increase significantly in the acute model, while mild hepatic steatosis (positive Oil Red O staining) appeared in the chronic model; 2. Molecular Indicators: - Lipoprotein Lipase (LPL) Activity: LPL activity in plasma and adipose tissue decreased by more than 60% compared to the control group (P<0.01); - Lipid Metabolism Genes: No significant changes in the expression of PPARγ and SREBP1c mRNA in the liver (distinguished from the diet-induced model); 3. Stability Validation: - Coefficient of variation of plasma TG after modeling in the same batch of mice < 20%, indicating good model repeatability.

*Precautions：

*References：Jadhav K,et,al. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Mol Metab. 2018 Mar;9:131-140.