Modeling Principle

The pig thyroiditis model is a SCI gold-standard large-animal autoimmune thyroiditis model constructed by active immunization with porcine thyroglobulin (pTg) combined with Freund’s adjuvant and high-iodine intervention, which accurately simulates the whole process of autoimmune disorder, chronic thyroid inflammatory injury and follicular destruction in clinical Hashimoto’s Thyroiditis (HT), and perfectly compensates for the species difference defects of rodent small animal models. Porcine thyroid tissue structure, thyroid globulin antigen epitopes, thyroid hormone secretion rhythm and autoimmune response mechanisms are highly homologous to humans, making it the most suitable non-human mammalian large-animal model for human thyroid diseases. As a specific autoantigen, exogenous porcine thyroglobulin effectively breaks immune tolerance, stimulates the body to produce abundant thyroid-specific autoantibodies TGAb and TPOAb. Continuous antigen stimulation induces Th1/Th17 immune imbalance, activates the NF-κB inflammatory pathway, and promotes massive secretion of pro-inflammatory factors such as IL-6, IL-1β, TNF-α and IL-17, mediating persistent infiltration of lymphocytes and macrophages in thyroid parenchyma. Meanwhile, high-iodine intervention further aggravates oxidative stress injury of thyroid follicular epithelial cells, accelerates follicular atrophy, disintegration and interstitial fibrosis, and gradually forms typical pathological phenotypes of Hashimoto’s thyroiditis including thyroid follicular destruction, diffuse lymphocyte infiltration, gland inflammatory swelling and hypothyroidism. With stable and slow pathological progression, controllable progressive immune injury and high phenotypic uniformity, this model highly recapitulates the chronic persistent characteristics of human autoimmune thyroiditis, serving as an authoritative SCI gold-standard large-animal model for preclinical translational research of thyroid autoimmune mechanisms, thyroid functional injury intervention and novel thyroid-protective drugs.

Modeling Success Criteria

Thyroid Macroscopic Phenotypes

The thyroid glands of the blank control group were uniform in size, ruddy in color, soft in texture, smooth in surface without swelling and congestion. The thyroid glands of the model group showed diffuse swelling, increased volume, dull and pale color, tough texture, mild congestion and edema on the surface, and significantly increased gland organ coefficients. The macroscopic inflammatory hyperplasia phenotype was extremely significantly different from that of the blank group, confirming the preliminary formation of the thyroiditis model.

Core Thyroid Function and Autoantibody Indexes

The serum thyroid-stimulating hormone (TSH) level of the model group was significantly upregulated, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were significantly decreased, presenting a typical clinical hypothyroidism functional phenotype. The titers of specific autoantibodies TGAb and TPOAb were extremely significantly increased, indicating complete breakdown of thyroid immune tolerance, which fully conforms to the core serological diagnostic criteria of Hashimoto’s thyroiditis and serves as the core quantitative gold standard for successful modeling.

Thyroid Histopathological Characteristics

HE staining of thyroid tissues showed typical pathological injuries of autoimmune thyroiditis: thyroid follicles were uneven in size and disordered in arrangement with atrophic and collapsed follicular lumens and significantly reduced colloid content; follicular epithelial cells presented degeneration, swelling, necrosis and shedding; thyroid stroma showed significant hyperplasia and vasodilation and congestion, with diffuse infiltration of a large number of lymphocytes and plasma cells and local lymphoid follicle formation, which accurately recapitulates the characteristic pathological changes of human Hashimoto’s thyroiditis with typical and highly specific modeling phenotypes.

Core Oxidative Stress and Inflammatory Indexes

The levels of oxidative damage products ROS and MDA in thyroid tissues of the model group were significantly increased, while the antioxidant capacities of SOD and GSH-Px were significantly decreased, resulting in severe thyroid oxidative stress imbalance. Core pro-inflammatory factors (TNF-α, IL-6, IL-1β, IL-17) were massively expressed, the NF-κB inflammatory pathway was continuously activated, and a stable chronic low-grade inflammatory microenvironment was formed in the thyroid, which fully conforms to the interactive oxidative-immune-inflammatory pathogenic mechanism of autoimmune thyroiditis and serves as the core academic basis for successful model construction.

Model Advantages

As a SCI-certified exclusive large-animal gold-standard model for Hashimoto’s thyroiditis, it breaks through the species defects of rodent small animals. Porcine thyroid immune mechanism, tissue structure and hormone metabolism are highly homologous to humans, and the modeling pathological process, immune disorder characteristics and functional decline rules are completely consistent with the real disease course of clinical HT patients. Adopting a compound modeling system of active antigen immunization combined with high-iodine induction, it features pure mechanism, strong specificity and no non-specific damage interference from exogenous drugs. It has a moderate modeling cycle, gradual and stable inflammatory injury, no sudden severe necrosis, excellent intra-group data uniformity and high reproducibility. It accurately simulates the complete pathogenic chain of immune tolerance breakdown, autoantibody elevation, Th17 inflammatory activation, follicular destruction and hypothyroidism occurrence, and is perfectly suitable for preclinical translational evaluation of drugs with thyroid immune regulation, anti-oxidation and anti-inflammation, thyroid follicle protection and hypothyroidism improvement effects. Large-animal model data have high credibility and far higher translational value than small animal models. With prominent project innovation and high recognition in high-score SCI journals, it is fully applicable for fund declaration, project opening, master and doctoral theses and thyroid translational medical research.

Research Applications

The pig thyroiditis model is corely applied to basic research on thyroid immune tolerance imbalance mechanism, Th1/Th17-mediated chronic thyroid inflammation, high-iodine induced thyroid follicular oxidative damage and autoantibody-mediated thyroid function decline. It is specially used for screening and evaluating traditional Chinese medicine compounds, natural active ingredients, small chemical molecules and thyroid-targeted preparations with effects of regulating thyroid immune balance, reducing autoantibody titers, anti-inflammation and anti-oxidation, protecting thyroid follicles and improving hypothyroidism. It is widely used in the exploration of Hashimoto’s thyroiditis pathogenic targets, elucidation of thyroid immune regulation mechanisms and large-animal preclinical translational verification of thyroid-protective drugs, serving as a scarce and essential standardized large-animal model in the fields of thyroid autoimmune diseases, endocrine pharmacology and immune regulation research.

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