He Jiangyan, Zhou Yiyuan, Zhang Taiwei, Zou Yan, Huang Hua
First Clinical Medical College of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Department of Obstetrics Healthy Pregnancy Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Ann Transl Med. 2022 Oct;10(20):1101. doi: 10.21037/atm-22-4079.
Subclinical hypothyroidism (SH) is common during pregnancy. It is not clear whether decidual cells in SH undergo pyroptosis during pregnancy. This study aimed to investigate the possible mechanism of Bushen Antai recipe (BAR) in the treatment of SH in early pregnancy and the relationship between SH during pregnancy and decidual cell pyroptosis through a rat model.
A total of 60 female rats were divided into control group, model group, levothyroxine (L-T4) group, low-dose BAR group (6 g/kg), medium-dose BAR group (12 g/kg), and high-dose BAR group (24 g/kg). The control group underwent pseudothyroidectomy, while the remaining groups established nonpregnant SH rat models. Except for the blank control group, rats were successfully established with SH models during pregnancy. The control group and the model group were treated with saline or BAR. The animals were sacrificed 12 hours after the last administration. The levels of serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of decidual nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, Caspase-1, and porin family proteins.
There was no significant difference in serum FT4 among groups (P>0.05). Compared with the control group, serum TSH, IL-1β, IL-18, and NLRP3, Caspase-1, and gasdermin D (GSDMD) proteins in the decidua of the model group were significantly increased (P<0.05). Compared with the model group, the L-T4 group and the high-dose BAR group could significantly decrease the levels of serum TSH, IL-1β, IL-18, and NLRP3, Caspase-1, and GSDMD in decidual tissue (P<0.05). The medium dose of BAR could significantly decrease the levels of TSH, NLRP3, Caspase-1, and GSDMD (P<0.05), and the low dose group of BAR significantly decreased the levels of TSH, NLRP3, and GSDMD (P<0.05). Among them, the high-dose group of BAR had the best reducing effect on IL-18, NLRP3, Caspase-1, and GSDMD.
The decidual cells of SH rats in early pregnancy underwent pyroptosis with a high inflammatory response. BAR could improve TSH level in SH during pregnancy, inhibit decidual cell pyroptosis, and reduce the expression of inflammatory factors.
亚临床甲状腺功能减退（SH）在孕期较为常见。目前尚不清楚孕期SH状态下的蜕膜细胞是否会发生焦亡。本研究旨在通过大鼠模型探讨补肾安胎方（BAR）治疗孕早期SH的可能机制以及孕期SH与蜕膜细胞焦亡之间的关系。
将60只雌性大鼠分为对照组、模型组、左甲状腺素（L-T4）组、低剂量BAR组（6 g/kg）、中剂量BAR组（12 g/kg）和高剂量BAR组（24 g/kg）。对照组行假甲状腺切除术，其余各组建立非孕SH大鼠模型。除空白对照组外，大鼠在孕期成功建立SH模型。对照组和模型组给予生理盐水或BAR。末次给药12小时后处死动物。采用酶联免疫吸附测定（ELISA）法检测血清促甲状腺激素（TSH）、游离甲状腺素（FT4）、白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）水平。采用蛋白质免疫印迹法检测蜕膜核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体、半胱天冬酶-1（Caspase-1）和孔蛋白家族蛋白的表达。
各组血清FT4水平差异无统计学意义（P>0.05）。与对照组相比，模型组蜕膜中血清TSH、IL-1β、IL-18以及NLRP3、Caspase-1和gasdermin D（GSDMD）蛋白显著升高（P<0.05）。与模型组相比，L-T4组和高剂量BAR组可显著降低蜕膜组织中血清TSH、IL-1β、IL-
