Résumé
Objective:To explore the mechanism of potassium iodide-induced pyrolysis of thyroid follicular cells.Methods:Thyroid gland tissue was obtained from patients with thyroid cancer (TC) coexisting with Hashimoto′s thyroiditis, and the tumor-adjacent Hashimoto′s thyroiditis tissue was used as the control. ELISA was used to detect the concentration of the pyroptosis inflammatory cytokines interleukin (IL)-1β and IL-18 in the tissues, and Western blotting was used to detect the activation of gasdermin (GSDM) proteins, a biomarker for pyroptosis. Thyroid follicular cells treated with different concentrations of potassium iodide, and IL-1β, IL-18, lactate dehydrogenase (LDH), GSDMD were measured. Transcriptome chip analysis was used to explore the differentially expressed genes involved in pyroptosis of thyroid follicular cells induced by potassium iodide treatment.Results:The levels of IL-1β and IL-18 cytokines in the tissues of patients with Hashimoto′s thyroiditis and thyroid cancer were higher than control tissues ( P<0.01), and the activation of the pyroptosis executive protein GSDMD was significant increased, while GSDME was not activated. IL-1β, IL-18, and LDH secretion were significantly increased in response to potassium iodide stimulation in thyroid follicular cells ( P<0.01) and GSDMD was cleaved, which indicated that potassium iodide induced the pyroptosis of thyroid follicular cells. Moreover, potassium iodide could activate NLRP3 inflammasomes to promotethe pyroptosis of thyroid follicular cells. Transcriptome chip analysis further found that PARP1 protein was highly upregulated by the stimulation of potassium iodide, and then enhanced the activity of nuclear factor-κB (NF-κB) transcription factor to induce pyroptosis. Conclusions:The findings in this study reveal that potassium iodide promotesthe pyroptosis of thyroid follicular cells through activating NF-κB-NLRP3 inflammasome, which may be a novel mechanism that promots the development of Hashimoto′s thyroiditis under the condition of excessive iodine intake. PARP1 is a pivotal protein that mediates the pyroptosis induced by potassium iodide and may be a potential therapeutic target to control Hashimoto′s thyroiditis progression.
Résumé
Eighty adult male Wistar rats were randomly divided into three groups: 1. In the experimental peptic ulcer group, 35 animals were induced to develop peptic ulcer by injecting 0.05 ml/kg of glacial acetic acid (more than 99%) into the submucosa of the stomach after laparotomy under aseptic conditions. 2.In the saline control group, 35 animals were injected with 0.05 ml/kg of saline into the submucosa of the stomach after laparotomy. 3.In the normal control group, 10 normal animals without any treatment were raised under the same condition as group 1 and group 2. The thyroid glands of three groups were taken at definite time intervals (1-28 days) after the operation. The right thyroids were prepared for cryostat sections after hexane quenching (-60℃) and subjected to the histochemical studies of acid phosphatase (AcP), alkaline phosphatase(AIP), a-glycerophosphate dehydrogenase (a-GPD), succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PD), and nonspecific esterase (NsE). The left thyroids were fixed in Carnoy's fluid, stained with HE and subjected to histological study. The reactions of enzymes of the follicular cells in the group 2 were weaker than those in the group 3 (normal control) during the period of 2-21 days after the operation. The follicular cells became flattened and follicular lumens increased in size. These changes recovered to normal on the 28th day after the operation. In the follicular cells of group 1. In which peptic ulcer developed after injection of glacial acetic acid, the reaction of A1P was weaker than those in the group 3, but stronger than those in the group 2. The reations of a-GPD, SDH, and G6PD were stronger than those in the group 2, and as well as those in group 3. The reaction of AcP was stronger than those in the group 2 and group 3 during the 6-21 days after the operation. The follicular cells in the group 1 became flattened and the follicular lumens increased in size only during the period of 4-10 days after the operation and recovered on the 14th day after the operation. These findings suggested that the thyroid follicular cells of rat involved in the metabolic activities of the repair of gastric ulcer.
Résumé
Fifty-two adult male rabbits, weighing 2～3kg, were divided into three groups. 1. Peptic ulcer were induced in 25 animals by injecting 0.3ml/kg of 40％ acetic acid into the submucosa of the stomach after laparotomy under aseptic conditions 2. 19 animals were operated as above but the same amount of normal saline were injcted instead of acetic acid 3. 8 normal rabbits were raised under the same conditions without any treatment and served as controls. The thyroid glands of three groups were taken at definite time intervals (1～40 days) after the operation. The right thyroids were prepared for cryostat sections after hexane quenching (-60℃) and subjected to enzyme histochemical studies. The left thyroids were fixed in Carnoy's fluid and subjected to histological and other histochemical studies. The following results were observed.The reactions of enzymes of follicular cells were weaker than the normal in the animals of the second group during the period of 3～21 days after the operation and injection of saline. The follicular ceils became flattened and follicular lumens increased in size. These changes began to show signs of recovery on the 28th day of the experiment. In the follicular cells of the first group of animals in which peptic ulcer developed after injection of acetic acid, the similar changes were observed as in the second groug of animals during the early period of 1～3 days after operation, but from 7 to 21 days after the operation, the reactions of Acid phosphatase, Succinate dehydrogenase, Glucose-6-phosphate dehydrogenase, Glycerphosphate dehydrogenase, Peroxidase, Adensine triphosphatase and Alkaline phosphatase were stronger and the sizes of follicular lumens were smaller, the colloid droplets were more numerous than those of the animals of the second group. These changes in the follicular cells of animals of the first group began to show signs of recovering toward norrnal on the 28 th day and became almost normal on the 40 th day after operation.These findings suggest that the thyroid follicular ceils were involved in the regulatory activities of the organism for the healing of the peptic ulcer.