Full
Outline
To study the effect of Buzhong Yiqi Decoction（补中益气汤）on the neural development of the offsprings of subclinical hypothyroidism（SCH）rats and explore its possible mechanism of action. At the same time，to compare the therapeutic effects of different doses of traditional Chinese medicine and Western medicine.
Adult female SD rats were used to establish an SCH model using total thyroidectomy and postoperative subcutaneous injection of L-T4，and the rats were randomly divided into the following 6 groups：sham surgery group，model group，low-dose group of Buzhong Yiqi Decoction［4.1 g/（kg·d）］，medium dose group of Buzhong Yiqi Decoction［8.19 g/（kg·d）］，high-dose group of Buzhong Yiqi Decoction［16.38 g/（kg·d）］，euthyrox group［4.5μɡ/（kg·d）］. After completing the SCH model，the model rats mated with normal male rats in a cage，and started administration 2 weeks before mating until sample collection. The samples were taken out from placental tissue at day 13 of pregnancy（E13）and brain tissue from offsprings at day 7 after birth（P7）. Water maze experiments were performed on offsprings at day 21. Radioimmunoassay（RIA）method was used to detect total thyroxine（T4）in serum. Enzyme linked immunosorbent assay（ELISA）was used to detect thyroid stimulating hormone（TSH）in serum. The mitochondrial morphology of brain tissue was observed through electron microscopy. Intracellular reactive oxygen species（ROS）was detected by DCFH-DA probe method. Mitochondrial DNA copy number was detected by using RT-PCR. DNA methyltransferase（DNMT）1，DNMT3a，DNMT3b，ten-eleven-translocation protein（TET）1 and TET2 were detected by the Western blotting（Wb）method.
Compared with those of the sham surgery group，the serum TSH levels of the model group were significantly increased，the Morris water maze scores of the 21-day offspring rats were significantly decreased，and the morphology of neuronal mitochondria was damaged under electron microscopy. On day 13，the levels of ROSincreased and the activities of mitochondrial respiratory chain complexes I and Ⅱ decreased in placental tissue and brain tissue of 7-day offspring rats. On day 7，the grayscale values of DNMT1，DNMT3a and DNMT3b proteins promoted methylation in brain tissue decreased，and the levels of TET1 and TET2 proteins regulated by reverse methylation increased. Compared with those of the model group，the medium dose and high dose groups of Buzhong Yiqi Decoction as well as the Western medicine group can reduce the elevated TSH levels in SCH rats，improve Morris water maze performance in 21-day offspring rats，reduce ROS levels and mitochondrial respiratory chain complex I and Ⅱ activity in brain tissue，improve the morphology of neuronal mitochondria in offspring rats，increase the grayscale values of methylated DNMT1，DNMT3a and DNMT3b proteins，and reduce the levels of TET1 and TET2 proteins regulated by reverse methylation.
Buzhong Yiqi Decoction can improve the learning and memory abilities of offsprings of maternal SCH rats，and its mechanism may be related to regulating methylation to improve mitochondrial energy metabolism and restore mitochondrial function.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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