中国临床医学2025，Vol.32Issue(5)：812-819,8.DOI:10.12025/j.issn.1008-6358.2025.20250481
Tepp-46对系统性硬皮病皮肤纤维化的影响
Effects of Tepp-46 on dermal fibrosis in systemic scleroderma
摘要
Abstract
Objective To explore the effects of Tepp-46,a pyruvate kinase M2(PKM2)agonist,on the skin fibrosis of patients with systemic scleroderma(SSc)and its therapeutic effect on the SSc mouse models.Methods Full-thickness skin tissues of SSc patients and healthy controls were taken,and the expression levels of PKM2 and α-smooth muscle actin(α-SMA)were detected using immunohistochemical staining.The skin primary fibroblasts were isolated from the tissues,and the PKM2 protein expression was detected using Western blotting.SSc fibroblasts were stimulated with Tepp-46 of different concentrations,and Western blotting was used to measure the expression of PKM2,collagen type Ⅰα1(ColⅠα1)and α-SMA protein after the stimulation.The C57BL/6 mice were randomly divided into three groups:control group,bleomycin(BLM)group and Tepp-46 group.BLM was injected subcutaneously to establish the SSc mouse model,at the same time,Tepp-46 treatment initiated in the Tepp-46 group.At 21 d after modeling,the mice were executed and their skins were taken.HE staining and Masson staining were used to analyze morphological changes of the skin.The immunohistochemical staining was used to examine the expression of PKM2 and α-SMA protein in the mouse skin.Western blotting was used to analyze the expression of ColⅠα1 and PKM2 in the mouse skin.Results Compared with the healthy controls,α-SMA protein expression in the dermis of SSc patients was higher,and PKM2 protein expression in the epidermis and dermis of SSc patients increased(P＜0.000 1).PKM2 protein expression in primary fibroblasts of SSc skin was higher than that of healthy controls(P＜0.01);after Tepp-46 stimulation,the levels of ColⅠα1 and α-SMA in SSc fibroblasts decreased(P＜0.01),but PKM2 protein was not affected.In the mice,HE and Masson stainings showed that compared with BLM group,the pathological changes of skin were alleviated in the Tepp-46 group.The immunohistochemical staining results showed the levels of PKM2 and α-SMA in the skin of Tepp-46 group were lower than those of the BLM group(P＜0.000 1).Western blotting results showed the level of ColⅠα1 in the Tepp-46 group was lower than that in the BLM group(P＜0.001).Conclusions The expression of PKM2 protein in SSc skin tissue and primary fibroblasts is up-regulated,and PKM2 agonist Tepp-46 can inhibit SSc skin fibrosis.关键词
丙酮酸激酶同工酶M2/系统性硬皮病/代谢/Tepp-46Key words
pyruvate kinase M2/systemic scleroderma/metabolism/Tepp-46分类
医药卫生引用本文复制引用
黄柳婷,林曼娜,王修远,黄俊霞,杨骥..Tepp-46对系统性硬皮病皮肤纤维化的影响[J].中国临床医学,2025,32(5):812-819,8.基金项目
国家自然科学基金面上项目(82373463,82073436).Supported by National Natural Science Foundation of China(82373463,82073436). （82373463,82073436）
