• Modeling Mechanism：

  Methylthiouracil inhibits thyroid function, lowers thyroid hormone levels, and thus reduces cholesterol catabolism (thyroid hormones promote the conversion of cholesterol into bile acids in the liver). In conjunction with a high-fat diet (high cholesterol + high saturated fat + bile acids), it further promotes cholesterol absorption and synthesis, collectively increasing serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Simultaneously, it activates the renin-angiotensin system (RAS), inducing vascular smooth muscle cell (VSMC) proliferation and lipid deposition, mimicking the pathological process of clinical diet-related hyperlipidemia and early atherosclerosis.

• Related Products：

  Methylthiouracil (T0304)

• Modeling Method：

  Experimental Subject：

  Rat, Wistar-Kyoto (WKY), Male, Body weight 150–190 g

  Dosage and Administration Route：

  ① Core Modelling (Combined Induction):
  - High-fat diet: containing 10% lard+4% cholesterol+0.5% taurocholate+85.5% basal diet, ad libitum feeding;
  - Drug intervention: Methylthiouracil at 80 mg/kg/day, dissolved in sterile physiological saline and administered via gastric lavage;
  ② Control treatment: Control group administered standard feed+equal volume saline solution via gastric lavage, with all other conditions identical;
  ③ Intervention validation group (optional):
  - Lipid-lowering/vascular protection intervention: Rosiglitazone, 4 mg/kg/day, administered via gastric lavage, commencing one month post-modelling and continuing for five months;

  Dosing Frequency and Duration Model：

  Once daily for 6 months

• Validation：

  1. Biochemical indicators: - Blood lipid levels: After 6 weeks of modeling, serum TC reached 4.66±0.56 mmol/L, TG reached 2.15±0.30 mmol/L, and LDL-C reached 1.93±0.21 mmol/L (significantly higher than the control group, p<0.01); - Local RAS: The concentration of angiotensin II (ANG II) in aortic tissue reached 4.72±0.91 ng/mg (compared to 2.45±0.10 ng/mg in the control group, p<0.01); 2. Molecular indicators: - Vascular receptors: The expression of angiotensin II type 1 receptor (AT₁R) mRNA and protein in aortic tissue was upregulated, and the expression of type 2 receptor (AT₂R) was synchronously increased (p<0.01); 3. Pathological indicators: - Vascular injury: HE staining showed lipid deposition in the aortic intima and VSMC. Proliferates and migrates to the intima, without typical atherosclerotic plaques (early lesions); Oil Red O staining shows the formation of lipid streaks in the intima; 4. Cell markers: - VSMC proliferation: ANG II-induced VSMC proliferation (MTT absorbance 0.51±0.02) was significantly higher than that of the control group (0.25±0.01, p<0.01).

*Precautions：

*References：Ren L,et,al. Vasculoprotective effects of rosiglitazone through modulating renin-angiotensin system in vivo and vitro. Cardiovasc Diabetol. 2011 Jan 26;10:10.