Effect of L-T4 gel combined with metformin on the content of Ach and MCT8 in hippocampus of rats with hypothyroidism
10.3760/cma.j.cn.115807-20220429-00109
- VernacularTitle:L-T4凝胶剂结合二甲双胍对甲减模型大鼠海马组织Ach、MCT8含量的影响
- Author:
Chunxia HONG
1
;
Zhaowei ZHANG
;
Honghua SHAO
;
Guangming CHEN
Author Information
1. 浙江大学医学院附属金华医院药学部，金华 321000
- Keywords:
L-T4 gel;
Metformin;
Decline of thyroid function;
Acetylcholine;
Monocarboxylate transporter 8
- From:
Chinese Journal of Endocrine Surgery
2022;16(6):736-741
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effects of L-T4 gel combined with metformin on Ach and MCT8 content in hippocampus of hypothyroidism model rats.Methods:40 rats were randomly divided into 5 groups, normal control group (CON group) , hypothyroidism group (Hypo group) , L-T4 replacement group (L-T4 group) , metformin treatment group (MET group) and combined treatment group (L-T4+MET group) by random number table. Rats in CON group were given normal drinking water, and rats in the other four groups were given drinking water containing 0.05% propylthiouracil for 6-week hypothyroidosis modeling. At the 5th week of modeling, rats in MET group were given 1ml/100g metformin solution by intragastric administration, and rats in L-T4 group were applied with L-T4 gel agent at a dose of 0.1g/100g. L-t4+MET group were treated with L-T4 gel and metformin solution. At the end of 6-week modeling, the blood of abdominal aorta was collected, and the hippocampal tissue of the brain was quickly separated on an ice platform. Meanwhile, the trachea and thyroid were cut out and photographed to record their size. They were stored in a -80℃ refrigerator or soaked in 4% paraformaldehyde for fixation and used for immunohistochemical staining. T-test was used to confirm the difference between the data of each group, one-way analysis of variance was used to compare the means between multiple groups, and chi-square test was used when the count data were expressed as percentage ( χ2) . P<0.05 was used to indicate statistical significance between the data, and the difference was statistically significant. Results:Nishner staining showed that the optical density of the Hypo group was lower than that of the CON group ( t=8.944, P<0.001) , the optical density of the MET group was higher than that of the Hypo group ( t=4.472, P<0.001) , and the optical density of the L-T4 group was higher than that of the Hypo group ( t=4.472, P<0.001) . The optical density of rats in the combined treatment group was higher than that in the Hypo group ( t=8.944, P<0.001) , and recovered to the level of the CON group ( P=1.000) . After 2 weeks of treatment, the total thyroxine level (TT4) of the Hypo group was lower than that of the CON group ( t=14.536, P<0.001) , and the TT4 level of the MET group was higher than that of the Hypo group ( t=6.924, P<0.001) . TT4 level of L-T4 group was higher than that of Hypo group ( t=4.892, P<0.001) , TT4 level of combined treatment group was higher than that of Hypo group ( t=12.890, P<0.05) , and recovered to the level of CON group ( t=0.494, P=0.709) . After the study, the thyroid tissue of each group was collected. The thyroid tissue weight of the Hypo group was higher than that of the CON group ( t=7.906, P<0.001) , the thyroid tissue weight of the MET group and L-T4 group was lower than that of the Hypo group (MET: t=2.000, P<0.001; L-T4: t=3.000, P<0.001) , but higher than that of the CON group (MET: t=3.000, P<0.001; L-T4: t=2.000, P<0.001) . The thyroid weight of L-T4+MET group was similar to that of CON group ( P=1.000) . HE staining showed that the size of thyroid follicles was different in the combined treatment group, and the number of glial and absorbed vacuoles basically recovered similar to that of CON. After treatment, the Ach level in the Hypo group was lower than that in the CON group ( t=3.618, P<0.001) , the Ach level in the MET group was higher than that in the Hypo group ( t=3.121, P=0.016) , the Ach level in the L-T4 group was higher than that in the Hypo group ( t=3.321, P=0.027) , and the Ach level in the combined treatment group was higher than that in the Hypo group ( t=3.202, P=0.001) . And recovered to the level of CON group ( t=3.362, P=0.605) . After treatment, the MCT8 level in the Hypo group was higher than that in the CON group ( t=11.254, P<0.001) , the MCT8 level in the MET group was lower than that in the Hypo group ( t=5.679, P<0.001) , and the MCT8 level in the L-T4 group was lower than that in the Hypo group ( t=5.813, P<0.001) . The MCT8 level of the combined treatment group was lower than that of the Hypo group ( t=8.624, P<0.001) , and recovered to the level of the CON group ( t=0.587, P=0.477) . Conclusion:L-T4 gel combined with metformin has a good therapeutic effect on hypothyroidism, which can increase the level of Ach and decrease the level of MCT8 in hippocampus.
