基于TGFβ1/Smad4信号通路探究人参四逆汤对亚临床甲状腺功能减退症大鼠心功能的影响  

Exploring the effect of Renshen Sini Decoction on the heart function of rats with subclinical hypothyroidism based on the TGFβ1/Smad4 signaling pathway

作　　者：高艳超 柳越 王岩 孙永艳 GAO Yan-chao;LIU Yue;WANG Yan(Department of Endocrinology,Chaoyang Second Hospital,Chaoyang122000,China)

机构地区：[1]朝阳市第二医院内分泌科,辽宁朝阳122000

出　　处：《中国实验诊断学》2022年第12期1839-1844,共6页Chinese Journal of Laboratory Diagnosis

摘　　要：目的 基于转化生长因子β1(TGFβ1)/Smad同源物4(Smad4)信号通路探究人参四逆汤对亚临床甲状腺功能减退症(SCH)大鼠心功能的影响。方法 随机数字表法将60只大鼠分为假手术组、SCH组、L-T4组、低剂量组、高剂量组、高剂量+LY2109761组(TGFβ1/Smad4通路抑制剂LY2109761),10只/组;甲状腺全切术及术后皮下注射L-T4建造SCH模型大鼠,成功后各组分别灌胃相应剂量药物或生理盐水,为期30 d,实验结束观察大鼠一般状况;检测大鼠心功能指标;ELISA法检测血清中促甲状腺激素(TSH)、总甲状腺素(TT4)水平;HE染色观察大鼠心肌组织病理学情况;Western blot检测心肌组织肌浆网钙离子ATP酶2a(serca2a)、Ryanodine受体(Ryr2)及TGFβ1/Smad4通路蛋白表达。结果 与假手术组相比,大鼠左心室收缩压(LVSP)、左室内压上升最大速率(LV+dp/dtmax)、心率(HR)、左室内压下降最大速率(LV-dp/dtmax)、serca2a、Ryr2蛋白水平在SCH组显著降低,左心室舒张末压(LVEDP)、TSH水平、心肌组织病理学程度、TGFβ1、Smad4蛋白水平在SCH组显著增加(P<0.05);与SCH组相比,LVSP、LV+dp/dtmax、HR、LV-dp/dtmax、serca2a、Ryr2蛋白水平在L-T4组、低剂量组、高剂量组及高剂量+LY2109761组显著增加,LVEDP、TSH水平、心肌组织病理学程度、TGFβ1、Smad4蛋白水平在L-T4组、低剂量组、高剂量组及高剂量+LY2109761组显著降低(P<0.05),且低剂量组与高剂量组间比较差异有统计学意义(P<0.05);与高剂量组相比,LVSP、+dp/dtmax、HR、-dp/dtmax、serca2a、Ryr2蛋白水平在高剂量+LY2109761组显著增加,LVEDP、TSH水平、心肌组织病理学程度、TGFβ1、Smad4蛋白水平在高剂量+LY2109761组显著降低(P<0.05)。结论 人参四逆汤通过抑制TGFβ1/Smad4通路改善SCH大鼠心功能。Objective Based on the transforming growth factor β1(TGFβ1)/mothers against DPP homolog 4(Smad4) signaling pathway, to explore the effect of Renshen Sini Decoction on the heart function of subclinical hypothyroidism(SCH) rats.Methods Sixty rats were divided into sham operation group, SCH group, L-T4 group, low dose group, high dose group, high dose+LY2109761 group(TGFβ1/Smad4 pathway inhibitor LY2109761) by random number table method, with 10 rats/group;total thyroidectomy and postoperative subcutaneous injection of L-T4 were performed to build SCH model rats, and after success, each group was given corresponding doses of drugs or normal saline for 30 days.After the experiment, the general conditions of the rats were observed;the indicators of rat heart function were detected;the levels of serum thyroid-stimulating hormone(TSH) and total thyroxine(TT4) were detected with ELISA method;the pathology of rat myocardial tissue was observed with HE staining;the expression of myocardial tissue sarcoplasmic reticulum calcium ATPase 2 a(serca2 a),Ryanodine receptor(Ryr2) and TGFβ1/Smad4 pathway proteins was detected with Western blot.Results Compared with the sham operation group, the left ventricular systolic pressure(LVSP),the maximum rate of left ventricular pressure increase(LV+dp/dtmax),heart rate(HR),and the maximum rate of left ventricular pressure decrease(LV-dp/dtmax),serca2 a and Ryr2 protein levels were significantly reduced in the SCH group, the left ventricular end diastolic pressure(LVEDP),TSH level, myocardial histopathology, TGFβ1 and Smad4 protein levels were significantly increased in the SCH group(P<0.05);compared with the SCH group, the LVSP,LV+dp/dtmax, HR, LV-dp/dtmax, serca2 a, and Ryr2 protein levels were significantly increased in the L-T4 group, low-dose group, high-dose group, and high-dose+LY2109761 group, the LVEDP,TSH level, myocardial histopathology, TGFβ1 and Smad4 protein levels were significantly reduced in the L-T4 group, low-dose group, high-dose group, and high-dose+LY2109761 gro

关 键 词：人参四逆汤 心功能 亚临床甲状腺功能减退症 转化生长因子β1 Smad同源物4 

分 类 号：R581.2[医药卫生—内分泌]