摘要
目的:探讨黄芪甲苷对桥本甲状腺炎(HT)大鼠甲状腺细胞凋亡及Ras同源基因家族成员A(RhoA)/Rho相关卷曲螺旋形成蛋白激酶2(ROCK2)通路的影响。方法:以皮下注射甲状腺球蛋白联合高碘饮水的方法诱导HT大鼠模型,随机分为模型组、黄芪甲苷(80 mg/kg)组、Rhosin(RhoA抑制剂,40 mg/kg)组、黄芪甲苷(80 mg/kg)+Rhosin(40 mg/kg)组(每组12只),另选出12只SD大鼠,正常饮水并皮下注射等剂量生理盐水作为对照组,经药物分组处理后,ELISA试剂盒测量血清抗甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)水平及炎症因子IL-6、IL-17、IL-1β含量;通过苏木精-伊红(HE)染色检测各组大鼠甲状腺组织病理形态变化;通过原位末端标记法(TUNEL)染色检测各组大鼠甲状腺细胞凋亡率;通过Western blot实验检测各组大鼠甲状腺组织RhoA/ROCK2通路蛋白表达。结果:与对照组相比,模型组大鼠甲状腺滤泡结构异常,部分萎缩或消失,排列紊乱,周围存在炎症细胞浸润,甲状腺组织有明显病理损伤,血清TGAb、TPOAb、IL-6、IL-17及IL-1β含量、甲状腺细胞凋亡率、甲状腺组织RhoA与ROCK2蛋白表达水平明显升高(P<0.05);与模型组相比,给药干预组大鼠甲状腺组织病理损伤均减轻,血清TGAb、TPOAb、IL-6、IL-17及IL-1β含量、甲状腺细胞凋亡率、甲状腺组织RhoA与ROCK2蛋白表达水平均降低(P<0.05);与黄芪甲苷组、Rhosin组分别相比,黄芪甲苷+Rhosin组大鼠甲状腺组织病理损伤均进一步减轻,血清TGAb、TPOAb、IL-6、IL-17及IL-1β含量、甲状腺细胞凋亡率、甲状腺组织RhoA、ROCK2蛋白表达水平均降低(P<0.05)。结论:黄芪甲苷可能通过下调RhoA/ROCK2通路表达,减轻甲状腺组织炎症损伤,抑制甲状腺细胞凋亡,改善大鼠HT症状。
Objective:To investigate the effect of astragalosideⅣon the apoptosis of thyroid cells in Hashimoto's thyroiditis(HT)rats and Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil containing kinase 2(ROCK2)pathway.Methods:The HT rat model was induced by subcutaneous injection of thyroglobulin combined with high iodine drinking water and randomly divided into model group,astragaloside(80 mg/kg)group,Rhosin(RhoA inhibitor,40 mg/kg)group,astragalosideⅣ(80 mg/kg)+Rhosin(40 mg/kg)group(12 rats in each group),another 12 SD rats were selected and drank water normally and injected the same dose of saline subcutaneously as control group.After the drugs were grouped and processed,the serum anti-thyroglobulin antibody(TGAb),anti-thyroid peroxidase antibody(TPOAb)levels and the inflammatory factors IL-6,IL-17,IL-1βcontents were measured by ELISA kits;the pathological changes of thyroid tissue in each group were detected by hematoxylin-eosin(HE)staining;the apopto⁃sis rate of rat thyroid cells in each group were detected by TUNEL staining;the expressions of RhoA/ROCK2 pathway proteins in thy⁃roid tissues of rats in each group were detected by Western blot.Results:Compared with the control group,the thyroid follicles in the model group had abnormal structure,some atrophy or disappearance,disordered arrangement,surrounding inflammatory cell infiltra⁃tion,and obvious pathological damage to the thyroid tissue,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1βlevels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were significantly increased(P<0.05);compared with model group,the pathological damage of the thyroid tissue of rats in the drug intervention group were reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1βlevels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05);compared with astragalosideⅣgroup and the Rhosin group respectively,the pathological damage of the thyroid tissue of rats in the astragalosideⅣ+Rhosin group were further reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1βlevels,thyroid cell apoptosis rate,thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05).Conclusion:AstragalosideⅣmay down-regulate the expression of RhoA/ROCK2 pathway to reduce the inflammatory injury of thyroid tissue,inhib⁃it thyroid cell apoptosis,and improve the symptoms of HT in rats.
作者
刘光霞
陈芳
高伟
王晓雅
卢亚敏
侯瞻
赵连春
LIU Guangxia;CHEN Fang;GAO Wei;WANG Xiaoya;LU Yamin;HOU Zhan;ZHAO Lianchun(Nuclear Medicine Discipline of Hebei Provincial People's Hospital,Shijiazhuang 050051,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第12期2517-2522,共6页
Chinese Journal of Immunology
基金
河北省医学科学研究课题计划项目(20210338)。
