L-T4凝胶剂结合二甲双胍对甲减模型大鼠海马组织Ach、MCT8含量的影响  

Effect of L-T4 gel combined with metformin on the content of Ach and MCT8 in hippocampus of rats with hypothyroidism

作　　者：洪春霞 张照伟 邵宏华 陈光明 Hong Chunxia;Zhang Zhaowei;Shao Honghua;Chen Guangming(Department of Pharmacy,Jinhua Hospital,School of Medicine,Zhejiang University,Jinghua 321000,China)

机构地区：[1]浙江大学医学院附属金华医院药学部,金华321000 [2]浙江大学医学院附属金华医院内分泌科,金华321000

出　　处：《中华内分泌外科杂志》2022年第6期736-741,共6页Chinese Journal of Endocrine Surgery

基　　金：浙江省医药卫生科技计划项目(2018RC080)。

摘　　要：目的研究L-T4凝胶剂联合二甲双胍对甲状腺功能减退(简称:甲减)模型大鼠海马乙酰胆碱(acetylcholine,Ach)和单羧酸转运蛋白8(monocarboxylate reansporter 8,MCT8)含量的影响。方法应用随机数字表法将40只大鼠随机分为5组,正常对照组(CON组)、甲减组(Hypo组)、L-T4替代治疗组(L-T4组)、二甲双胍治疗组(MET组)、联合治疗组(L-T4+MET组)。CON组大鼠进行正常饮水,其余4组大鼠饮用含有0.05%丙硫氧嘧啶的饮用水,进行6周甲减造模。在造模第5周时,MET组大鼠进行灌胃1ml/100g二甲双胍溶液,L-T4组大鼠应用L-T4凝胶剂涂抹背部脱毛处,涂抹剂量为0.1g/100g,L-T4+MET组大鼠进行L-T4凝胶剂涂抹和二甲双胍溶液(1ml/100g)灌胃治疗。6周造模结束后,收集腹主动脉血液,在冰台上将大脑海马组织快速分离,同时将气管和甲状腺剪下拍照纪录大小,且将其储存在-80℃冰箱中或浸泡在4%多聚甲醛固定,用于免疫组化染色。使用t检验确认各组数据之间的差异性,多组间均数比较应用单因素方差分析,当计数资料以百分率表示时使用χ2。以P<0.05表示差异具有统计学意义。结果尼氏染色结果显示,Hypo组的光密度值低于CON组(t=8.944,P<0.001),MET组大鼠光密度较Hypo组高(t=4.472,P<0.001),L-T4组大鼠光密度值较Hypo组大鼠高(t=4.472,P<0.001),联合治疗组大鼠光密度值较Hypo组大鼠高(t=8.944,P<0.001),且恢复至CON组水平(P=1.000)。经过2周治疗后,Hypo组的总甲状腺素水平(total thyroxine level,TT4)水平低于CON组(t=14.536,P<0.001),MET组大鼠TT4水平较Hypo组高(t=6.924,P<0.001),L-T4组TT4水平较Hypo组大鼠高(t=4.892,P<0.001),联合治疗组大鼠TT4水平较Hypo组大鼠高(t=12.890,P<0.05),且恢复至CON组水平(t=0.494,P=0.647)。研究结束后,收集各组大鼠的甲状腺组织,Hypo组大鼠甲状腺组织重量高于CON组(t=7.906,P<0.001),MET组和L-T4组大鼠甲状腺组织重量低于Hypo组(MET:t=2.000,P<0.001;L-T4:t=3.000,P<0.001),但Objective To study the effects of L-T4 gel combined with metformin on Ach and MCT8 content in hippocampus of hypothyroidism model rats.Methods 40 rats were randomly divided into 5 groups,normal control group(CON group),hypothyroidism group(Hypo group),L-T4 replacement group(L-T4 group),metformin treatment group(MET group)and combined treatment group(L-T4+MET group)by random number table.Rats in CON group were given normal drinking water,and rats in the other four groups were given drinking water containing 0.05%propylthiouracil for 6-week hypothyroidosis modeling.At the 5th week of modeling,rats in MET group were given 1ml/100g metformin solution by intragastric administration,and rats in L-T4 group were applied with L-T4 gel agent at a dose of 0.1g/100g.L-t4+MET group were treated with L-T4 gel and metformin solution.At the end of 6-week modeling,the blood of abdominal aorta was collected,and the hippocampal tissue of the brain was quickly separated on an ice platform.Meanwhile,the trachea and thyroid were cut out and photographed to record their size.They were stored in a-80℃refrigerator or soaked in 4%paraformaldehyde for fixation and used for immunohistochemical staining.T-test was used to confirm the difference between the data of each group,one-way analysis of variance was used to compare the means between multiple groups,and chi-square test was used when the count data were expressed as percentage(χ2).P<0.05 was used to indicate statistical significance between the data,and the difference was statistically significant.Results Nishner staining showed that the optical density of the Hypo group was lower than that of the CON group(t=8.944,P<0.001),the optical density of the MET group was higher than that of the Hypo group(t=4.472,P<0.001),and the optical density of the L-T4 group was higher than that of the Hypo group(t=4.472,P<0.001).The optical density of rats in the combined treatment group was higher than that in the Hypo group(t=8.944,P<0.001),and recovered to the level of the CON group(P=1.000).After

关 键 词：L-T4凝胶剂 二甲双胍 甲状腺功能衰退 乙酰胆碱 单羧酸转运蛋白8 

分 类 号：R581.2[医药卫生—内分泌] R-332[医药卫生—内科学]