摘要
目的研究雷公藤多苷对Graves病小鼠甲状腺功能和氧化应激状态的作用。方法60只BALB/c小鼠,12只作为对照组,其余48只小鼠采用Ad-TSHR 289免疫的方法建立Graves病模型,造模完成后随机分为4组,每组12只,分别为模型组,雷公藤多苷低、中、高剂量组。雷公藤多苷低、中、高剂量组分别按照20、40、80 mg/kg的剂量灌胃给予小鼠雷公藤多苷,对照组及模型组灌胃给予小鼠等量生理盐水,每天给药1次。连续给药21 d后,检测各组小鼠血清TRAb、T 4、T 3、ALT、AST、ALP水平,检测小鼠肝脏SOD活性、GSH及MDA水平,计算各组小鼠甲状腺脏器指数,苏木精-伊红染色法进行小鼠甲状腺组织病理学检查,Western blot检测小鼠甲状腺组织细胞PI3K、AKT、mTOR水平。结果与对照组比较,模型组Graves病小鼠血清TRAb、T 4、T 3、ALT、AST、ALP、MDA水平均升高(P<0.05),肝脏SOD活性及GSH水平均降低(P<0.05),小鼠甲状腺组织发生明显病理学改变,甲状腺组织细胞PI3K、AKT、mTOR水平均升高(P<0.05);与模型组相比,雷公藤多苷各剂量组小鼠血清TRAb、T 4、T 3、ALT、AST、ALP、MDA水平均降低(P<0.05),肝脏SOD活性及GSH水平均升高(P<0.05),小鼠甲状腺组织病理学明显改善,甲状腺组织细胞PI3K、AKT、mTOR水平均降低(P<0.05),且各项指标均表现出一定的剂量依赖性。结论雷公藤多苷能够改善Graves病小鼠甲状腺功能和氧化应激状态,其作用机制可能与调节PI3K/AKT/mTOR通路有关。
Objective To study the effects of tripterygium wilfordii polyglycosides on thyroid function and oxidative stress in mice with Graves disease.Methods Totally 60 BALB/c mice were chsoen,12 as control group,and the other mice were immunized with Ad-TSHR 289 to establish the model of Graves disease.The 48 mice were randomly divided into 4 groups with 12 mice in each group,including model group and low-dose,middle-dose and high-dose Tripterygium wilfordii polyglycosides groups.Low-dose,middle-dose and high-dose Tripterygium wilfordii poly-glycosides groups were given 20 mg/kg,40 mg/kg and 80 mg/kg of Tripterygium wilfordii polyglycosides,respectively,while the mice in control group and model group were given the same amount of normal saline once daily for 21 d.After treatment.the serum levels of TRAb,T 4,T 3,ALT,AST and ALP were measured;the SOD activity,GSH and MDA levels in liver were measured;the thyroid organ index was calculated;hematoxylin-eosin staining method was used for the thyroid histopathological examination in mice.The levels of PI3K,AKT and mTOR in thyroid tissue cells of mice were detected by Western blot.Results Compared with control group,the levels of serum TRAb,T 4,T 3,ALT,AST,ALP and MDA in model group were significantly increased(P<0.05),while the activity of SOD and the level of GSH in liver were significantly decreased(P<0.05);there were obvious pathological changes in thyroid tissue of mice,and the levels of PI3K,AKT and mTOR in thyroid tissue were significantly increased(P<0.05).Compared with model group,the levels of serum TRAb,T 4,T 3,ALT,AST,ALP and MDA in tripterygium wilfordii polyglycosides groups were decreased(P<0.05),while the activity of SOD and the level of GSH in liver were significantly increased(P<0.05);the histopathology of thyroid tissue in mice was significantly improved,and the levels of PI3K,AKT and mTOR in thyroid tissue cells were significantly decreased(P<0.05),and all the indexes showed a dose-dependent trend.Conclusion Tripterygium wilfordii polyglycosides can improve the thyroid function and oxidative stress in mice with Graves disease,which may be related to the regulation of PI3K/AKT/mTOR pathway.
作者
张洁
王思瑶
陆春晖
罗荔
ZHANG Jie;WANG Si-yao;LU Chun-hui;LUO Li(Department of Endocrinology,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
出处
《实用药物与临床》
CAS
2020年第8期688-692,共5页
Practical Pharmacy and Clinical Remedies
基金
新疆维吾尔自治区自然科学基金(2018D01C175)。
