摘要
目的:探讨海藻-甘草剂量为《中华人民共和国药典》2015年版规定高限剂量2倍的条件下,海藻-甘草反药组合在海藻玉壶汤抗丙硫氧嘧啶(PTU)致大鼠甲状腺肿大中的作用。方法:Wistar雄性大鼠84只,按体质量随机分为对照组、模型组、阳性药组(优甲乐)、海藻玉壶汤全方组(简称“全方组”)、海藻玉壶汤去海藻组(简称“去海藻组”)、海藻玉壶汤去甘草组(简称“去甘草组”)、海藻玉壶汤去海藻及甘草组(简称“去藻草组”),每组12只。造模期间,除对照组外,其余各组大鼠灌胃给予PTU(10 mg·kg^(-1)),每日1次,共14 d。模型制备成功后,对照组与模型组大鼠灌胃给予去离子水,阳性药组大鼠给予优甲乐(20μg·kg^(-1)),其余各给药组给予相应中药煎液(给药剂量为全方组12.06 g·kg^(-1)、去海藻组9.9 g·kg^(-1)、去甘草组10.26 g·kg^(-1)、去藻草组8.1 g·kg^(-1)),每日给药1次,持续28 d。治疗期间,每隔1 d,除对照组外,其余各组大鼠均灌胃给予PTU以维持模型稳定,剂量依前。给药结束后计算各组大鼠的甲状腺系数;光镜下观察甲状腺组织形态;放射免疫法检测血清中三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平。结果:与对照组比较,各组大鼠甲状腺系数显著升高(P<0.01);与模型组比较,各中药煎液给药组大鼠甲状腺系数显著降低(P<0.01)。光镜下观察大鼠甲状腺组织形态,结果显示,与对照组比较,模型组与阳性药组变化最为显著,甲状腺组织小叶排列紊乱,结构不清,细胞核数目增多(P<0.05),上皮细胞增生肥大,细胞直径增加(P<0.05),滤泡腔大小不一,形状各异,面积显著减小(P<0.05),其余各给药组大鼠甲状腺组织的病变均有一定减轻,其中全方组大鼠甲状腺组织形态与对照组最为接近。与对照组比较,模型组大鼠血清中T3、T4水平显著降低(P<0.05),TSH水平显著升高(P<0.05)。与模型组比较,阳性药组、全方组大鼠血清T3、T4水平显著升高(P<0.05),TSH水平有降低趋势,但差异无统计学意义。结论:海藻玉壶汤全方及去掉1味或2味反药组合能回调甲状腺肿大大鼠甲状腺系数,改善甲状腺组织病理形态及恢复血清中激素水平,且全方组优于全方去掉1味或2味反药组,由此说明,海藻-甘草反药组合是海藻玉壶汤中关键的药对,对于甲状腺肿大的治疗缺一不可。
Objective:To investigate the effect of antagonistic Sargassum-Glycyrrhizae Radix et Rhizoma combination in Haizao Yuhu Decoction(HYD)on goiter rats under the condition that the doses of two medicinals are twice the upper limits in the 2015 edition of Chinese Pharmacopoeia.Method:Rats(n=84)were randomized into seven groups:blank(deionized water),model(deionized water),positive control(20μg·kg^(-1) euthyrox),HYD(12.06 g·kg^(-1)),HYD without Sargassum(9.9 g·kg^(-1)),HYD without Glycyrrhizae Radix et Rhizoma(10.26 g·kg^(-1)),and HYD without Sargassum and Glycyrrhizae Radix et Rhizoma(8.1 g·kg^(-1)),with 12 in each group.For modeling,all the rats were given(ig)propylthiouracil(PTU,10 mg·kg^(-1))for fortnight once a day except the blank group(normal saline).After modeling,the administration(once a day)lasted 28 days for each group.During the administration,rats(except for the blank group)received(ig)PTU(10 mg·kg^(-1))every other day in an effort to maintain model stability.After treatment,thyroid index of rats was calculated and pathological morphology of thyroid was observed under light microscope.Thyroid function-related indexes such as triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4),and thyroid-stimulating hormone(TSH)in serum were detected by radioimmunoassay.Results:Thyroid index was lower in the blank group than in other groups(P<0.01)and lower in the model group than in all the HYD groups(P<0.01).As for the pathological morphology of thyroid,the changes in the model group and positive control group were most significant compared with blank group,as manifested by the disordered lobules of thyroid gland with unclear internal structure(P<0.05),increased number of follicular epithelial cell nuclei,elevated cell diameter(P<0.05),and follicular cavities of diversified size and forms with reduced area(P<0.05).These changes were rectified to different degrees in other groups,particularly the HYD group.Model group had lower serum levels of T3 and T4(P<0.05)and higher level of TSH(P<0.05)than the blank group.The positive control group and HYD group had higher serum levels of T3 and T4(P<0.05)and insignificantly lower level of TSH than the model group.Conclusion:HYD containing the antagonistic medicinal combination,either of the antagonistic medicinals,or neither of the medicinals can all recover the thyroid index,improve the pathological morphology of thyroid,and restore the serum levels of thyroid function-related indexes in PTU-induced goiter rats,especially the HYD containing both Sargassum and Glycyrrhizae Radix et Rhizoma.Therefore,the antagonistic Sargassum and Glycyrrhizae Radix et Rhizoma are the key pair in HYD,which is indispensible in the treatment of goiter in rats.
作者
王鑫
葛超冉
霍敏
贺佳
陈丰
李娜
柳海艳
修琳琳
陈绍红
许皖
吕艳敏
葛东宇
董瑞娟
钟赣生
WANG Xin;GE Chao-ran;HUO Min;HE Jia;CHEN Feng;LI Na;LIU Hai-yan;XIU Lin-lin;CHEN Shao-hong;XU Wan;LYU Yan-min;GE Dong-yu;DONG Rui-juan;ZHONG Gan-sheng(Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《中国现代中药》
CAS
2021年第8期1391-1398,共8页
Modern Chinese Medicine
基金
国家重点基础研究发展计划(“973”计划)项目(2011CB505306)
北京中医药大学校级科研纵向发展基金项目(2019-ZXFZJJ-066)。
关键词
海藻玉壶汤
甲状腺肿大大鼠
甲状腺系数
甲状腺功能
病理形态
Haizao Yuhu Decoction
goiter rats
thyroid index
thyroid function-related indexes
pathological morphology
