Endocrine Abstracts

Objective

In BALB/c mice with GD model, the TSHR and ICAM-1 were targeted for treatment, and new approaches to GD targeted therapy were explored.

Methods

The siRNA targeting TSHR and the ICAM-1 mAb specifically binding ICAM-1 were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group, with 10 mice in each group, and 10 normal mice in a control group. Serum T₄, TSH, TSAb and TSBAb were measured before and after treatment. At the end of the treatment, weight and heart rate of each group were measured, thyroid uptake of ^99mTcO₄^-, thyroid size and pathological changes were evaluated.

Results

After three treatments, the weights of mice in the siRNA group and the ICAM-1 mAb group were still lower than that of normal mice. The heart rate of the mice in the siRNA group and the ICAM-1 mAb group were significantly lower than that of the GD mice. Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, T₄, TSAb and TSBAb levels in both the siRNA group and the ICAM-1 mAb group were significantly decreased, while serum TSH levels were significantly increased, and the above changes were statistically different from those in GD mice. There was no significant difference in the decreased levels of T₄ and TSBAb between the siRNA group and the ICAM-1 mAb group. The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA. After treatment, both the siRNA group and the ICAM-1 mAb group showed reduced uptake ability of ^99mTcO₄–in part of the thyroid lobes, and reduced enlargement degree of the same lobes. The thyroid pathology of the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice.

Conclusions

Both the siRNA targeting TSHR and the ICAM-1 mAb specifically binding to ICAM-1 have therapeutic effects on GD model mice. The siRNA was better at controlling heart rate, and the ICAM-1 mAb was better at increasing TSH and decreasing TSAb. Each of the above treatment methods had its own advantages and had good application prospects, which can provide new ideas for GD targeted therapy.