摘要
目的基于抗氧化作用探讨海藻消瘤胶囊对丙硫氧嘧啶(PTU)诱导的甲状腺功能减退大鼠模型的作用机制。方法50只雄性大鼠随机分为对照组、模型组、海藻消瘤胶囊高剂量、低剂量组和西药组。除对照组外,其余组连续21 d灌胃PTU(10 mg·kg^(-1))造模。随后,高、低剂量组分别给予海藻消瘤胶囊0.702 g·kg^(-1)和1.404 g·kg^(-1),西药组给予左甲状腺素钠50μg·kg^(-1),对照组和模型组给予生理盐水,连续14d。治疗后,评估大鼠体质量、甲状腺脏器指数、甲状腺体积及病理形态;检测血清促甲状腺激素(TSH)、甲状腺激素(T3、T4)水平,甲状腺组织谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量,甲状腺组织4-羟基壬烯醛(4-HNE)、Kelch样ECH相关蛋白1(Keap1)、Nrf2、HO-1蛋白表达。结果与对照组比较,模型组大鼠甲状腺肿大明显(P<0.01),血清TSH水平升高,T3、T4水平降低(P<0.01),甲状腺组织GSH、SOD降低(P<0.01),MDA升高(P<0.01),且甲状腺组织4-HNE、Keap1蛋白表达升高,Nrf2、HO-1蛋白表达降低(P<0.01);与模型组比较,高剂量组上述指标均有显著性改善(P<0.05,P<0.01)。结论海藻消瘤胶囊通过激活Nrf2/HO-1通路能有效抑制PTU诱导的甲状腺功能减退。
Objective To investigate the mechanism by which Haizao Xiaoliu Capsule(海藻消瘤胶囊,HZXLC)exerts protective effects against propylthiouracil(PTU)-induced hypothyroidism in rats,focusing on their antioxidant properties.Methods Fifty male rats were randomly assigned to five groups:the control,model,high-dose HZXLC,low-dose HZXLC,and levothyroxine sodium(LT4)groups.Except for the control group,all rats received PTU(10 mg·kg^(-1))via gavage for 21 consecutive days to establish the hypothyroidism model.Thereafter,the high-dose and low-dose groups were administered HZXLC at 1.404 g·kg^(-1)and 0.702 g·kg^(-1),respectively.The LT4 group received levothyroxine sodium(50μg·kg'),while the control and model groups were given normal saline for 14 consecutive days.After treatment,body weight,thyroid index,thyroid volume,and histopathological changes were assessed.Serum levels of thyroid-stimulating hormone(TSH)and thyroid hormones(T3,T4)were measured.The levels of glutathione(GSH),superoxide dismutase(SOD),and malondialdehyde(MDA)in the thyroid tissues were determined.Western blot(WB)was used to detect the protein expression of 4-hydroxynonenal(4-HNE),Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)in the thyroid tissues.Results Compared with the control group,the model group exhibited thyroid enlargement(P<0.01),elevated serum TSH,and reduced T3 and T4 levels(P<0.01).Thyroid tissue analysis revealed decreased GSH and SOD levels(P<0.01)and increased MDA levels(P<0.01).Additionally,4-HNE and Keapl protein expression was up-regulated,whereas Nrf2 and HO-1 expression was down-regulated(P<0.05,P<0.01).Compared with the model group,the high-dose HZXLC group demonstrated significant regulation of these parameters(P<0.05,P<0.01).Conclusion HZXLC exerts protective effects against PTU-induced hypothyroidism,potentially by activating the Nrf2/HO-1 pathway to mitigate oxidative stress.
作者
张怡君
萧闵
胡冰冰
祝中意
杨金蓉
胡然
ZHANG Yijun;XIAO Min;HU Bingbing;ZHU Zhongyi;YANG Jinrong;HU Ran(Hubei Minzu University,Enshi 445000,China;Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Shizhen Laboratory,Wuhan 430065,China;Xiangyang Municipal Hospital of Traditional Chinese Medicine,Xiangyang Traditional Chinese Medicine Research Institute,Xiangyang 441000,China;Xiangyang Integrated Traditional Chinese and Western Medicine Hospital,Xiangyang 441000,China)
出处
《时珍国医国药》
北大核心
2025年第12期2250-2256,共7页
Lishizhen Medicine and Materia Medica Research
基金
湖北省科技厅科技项目(2022BCE055)。
