参桂甲减丸对老龄甲状腺功能减退大鼠心肌纤维化及TGF-β1/Smads信号通路的影响  

Effects of Shengui Jiajian Pills on myocardial fibrosis and TGF-β1/Smads signaling pathway in aged hypothyroid rats

作　　者：王登坤 熊鹏 苟于瑞 张敏 白永胜 Wang Dengkun;Xiong Peng;Gou Yurui;Zhang Min;Bai Yongsheng(Department of Geriatrics,Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China;The First Clinical Medical College of Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学附属医院老年病科,咸阳712000 [2]陕西中医药大学第一临床医学院,咸阳712000

出　　处：《国际中医中药杂志》2024年第12期1583-1592,共10页International Journal of Traditional Chinese Medicine

基　　金：陕西省中医药管理局中医药科研项目(SZY-KJCYC-2023-031);陕西省咸阳市重点研发计划科研项目(S2023-ZDYF-SF-2093);陕西中医药大学国科金培育项目(2023GP43)。

摘　　要：目的研究参桂甲减丸对老龄甲状腺功能减退性心脏损伤大鼠心肌纤维化及TGF-β1/Smads信号通路的影响,探讨参桂甲减丸通过TGF-β1/Smads通路治疗甲状腺功能减退性心脏病的作用机制。方法将60只SD大鼠按随机数字表法分为空白组、模型组、左甲状腺素钠组及参桂甲减丸低、中、高剂量组,每组10只。采用自由饮用含0.1%丙基硫氧嘧啶(PTU)的双蒸水10周制备老年甲状腺功能减退性心脏损伤大鼠模型。各组大鼠灌胃相应药物,1次/d,持续6周。末次灌胃后,行心电图检测;HE染色观察心脏组织病理改变;苦味酸-天狼猩红染色检测心脏组织纤维化;TUNEL染色观察心肌细胞凋亡情况;ELISA法检测血清促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平及脑利尿钠肽(BNP)、肌酸激酶同工酶MB(CK-MB)、LDH水平;Western blot法检测心脏组织TGF-β1、p-Smad2、p-Smad3、α-平滑肌肌动蛋白(α-SMA)、MMP-1、基质金属蛋白酶抑制剂-1(TIMP-1)、Bax、Caspase-3相对表达;免疫荧光染色检测心脏组织中TGF-β1、Smad3、α-SMA、MMP-1阳性表达。结果与模型组比较,参桂甲减丸各剂量组大鼠心肌细胞损伤均有改善,心肌纤维化面积占比、心肌细胞凋亡率降低(P<0.05),血清TSH、BNP、CLD、HK-MB水平降低(P<0.05);参桂甲减丸中、高剂量组FT3、FT4水平升高(P<0.05),TGF-β1、Smad3、α-SMA、MMP-1阳性表达降低(P<0.05),TGF-β1、p-Smad3、MMP-1、Bax、Caspase-3蛋白表达降低(P<0.05),TIMP-1表达升高(P<0.05),参桂甲减丸中剂量组Smad7表达升高(P<0.05)。结论参桂甲减丸可能通过调控TGF-β1/Smad3信号通路减少心肌胶原纤维沉积,进而一定程度上逆转甲减性心肌损伤的病理特征,且中、高剂量组改善作用较为明显。Objective To study the effects of Shengui Jiajian Pills on myocardial fibrosis and the transforming growth factor-β1(TGF-β1)/Smads signaling pathway in elderly rats with hypothyroidism;To preliminarily explore the mechanism of Shengui Jiajian Pills in treating hypothyroid heart disease through the TGF-β1/Smads pathway.Methods Totally 60 SD rats were randomly divided into normal group,model group,sodium levothyroxine group,and Shengui Jiajian Pills low-,medium-,and high-dosage groups,with 10 rats in each group.A model of elderly hypothyroid heart injury in rats was prepared by freely drinking 0.1%propylthiouracil(PTU)for 10 weeks.Each group of rats was gavaged with the corresponding drug once a day for 6 weeks.After the last gastric lavage,an electrocardiogram was performed,hematoxylin-eosin staining(HE)was used to observe pathological changes in the heart tissue;bitter acid-toluidine blue staining was used to detect fibrosis of the heart tissue;TUNEL staining was used to observe myocardial cell apoptosis;Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of thyroid stimulating hormone(TSH),free triiodothyronine(FT3),free thyroxine(FT4)in the serum,as well as brain natriuretic peptide(BNP),creatine kinase isoenzymes MB(CK-MB),and lactate dehydrogenase(LDH);Western blot was used to detect the relative expressions of TGF-β1,p-Smad2,p-Smad3,α-smooth muscle actin(α-SMA),matrix metalloproteinase-1(MMP-1),TIMP1,Bax,and Caspase-3 in the heart tissue;and immunofluorescence was used to detect the positive expressions of TGF-β1,Smad3,α-SMA,and MMP-1 in the heart tissue.Results Compared with the model group,the inflammatory cell infiltration and cell damage in the heart of rats in each dosage group of Shengui Jiajian Pills were improved,the myocardial fibrosis area ratio was significantly reduced(P<0.05),and the myocardial cell apoptosis rate significantly decreased(P<0.05),the levels of TSH,BNP,CLD,and HK-MB in serum significantly decreased(P<0.05).The levels of FT3 and FT4 increased in the Shengu

关 键 词：甲状腺功能减退症 甲状腺功能减退性心脏病 参桂甲减丸 TGF-β1/Smads 心肌纤维化 大鼠 

分 类 号：R285.5[医药卫生—中药学]