Effects of atorvastatin calcium on thyroid function,immune response and JNK/p38 MAPK signaling pathway in rats with hypothyroidism
- VernacularTitle:阿托伐他汀钙对甲状腺功能减退大鼠甲状腺功能、免疫应答及JNK/p38 MAPK信号通路的影响
- Author:
Haoyun ZHANG
1
;
Mengxi LI
;
Shujuan KANG
;
Bingjie ZHANG
;
Xianqiao LI
;
Tieying SHAN
;
Hao LI
;
Xiaoyan LIU
;
Zhiqiang CUI
Author Information
- Keywords: hypothyroidism; atorvastatin calcium; c-Jun N-terminal kinase/p38 mitogen-ac-tivated protein kinase signaling pathway; thyroid stimulating hormone; interleukin
- From: Journal of Clinical Medicine in Practice 2024;28(16):49-55
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the effects of atorvastatin calcium on thyroid function,im-mune response and C-Jun N-terminal kinase/p38 mitogen-activated protein kinase(JNK/p38 MAPK)signaling pathway in rats with hypothyroidism.Methods A total of 30 healthy adult male SD rats were randomly divided into control group,hypothyroid group(PTU group)and atorvastatin calcium treatment group(ACT group),with 10 rats in each group.Rats in the PTU group and the ACT group were injected with PTU subcutaneously at the dorsum of the neck every day for 28 consecutive days;instead of PTU,rats in the control group were injected subcutaneously with 0.3 mL of saline.After 2 weeks of PTU treatment,rats in the ACT group were gavaged with 3 mL of atorvastatin calcium sa-line solution(containing 5 mg/kg of atorvastatin calcium),which was administered once daily;the control group was gavaged with an equal amount of saline in the same way.The body weight,food intake and water intake of rats were measured weekly.The histopathological changes of the thyroid gland were observed in histopathological sections of rats in each group.Enzyme-linked immunosor-bent assay(ELISA)was performed to determine the levels of triiodothyronine(T3),thyroxine(T4),thyroid stimulating hormone(TSH),interferon γ(IFN-γ)and interleukin-4(TL-4)in ser-um;quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was performed to de-tect the mRNA expression levels of IFN-γ,IL-10,Foxp3 and IL-4;western blot was performed to determine the levels of p-JNK/JNK and p-p38/p38 MAPK.Results Compared with control group,PTU-induced hypothyroidism rats showed a significant decrease in body mass and food and water consumption(P＜0.05).After 2 weeks of treatment with atorvastatin calcium,the body mass loss of PTU rats was inhibited,food and water consumption was improved,and the differences were sta-tistically significant(P＜0.05).Atorvastatin calcium was able to significantly increase the serum T3 and T4 levels and decrease the serum TSH level in hypothyroid rats(P＜0.05).Atorvastatin calcium treatment was able to significantly alleviate histopathological changes such as follicular cell proliferation and related hypertrophy induced by PTU,and increase follicular size(P＜0.05).Af-ter treatment with atorvastatin calcium,the spleen mass of PTU rats increased significantly,and the expression of IFN-γ mRNA in hypothyroid rats decreased significantly,but the expression levels of IL-10 mRNA,Foxp3 mRNA and IL-4 mRNA increased significantly(P＜0.05).After treatment with atorvastatin calcium,the levels of p-JNK/JNK and p-p38/p38 MAPK in thyroid tissue of hypo-thyroid rats decreased significantly(P＜0.05).Conclusion Atorvastatin calcium treatment for hy-pothyroidism has the function of promoting the normalization of thyroid hormone imbalance,balan-cing Th1/Th2 cytokines,and inhibiting the activation of JNK/p38 MAPK signaling pathway.
