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专家账号密码找回目的 探讨圣草酚对转化生长因子β1（TGF⁃β1）诱导的人皮肤成纤维细胞（HSF）的增殖、氧化应激反应及 TGF⁃β1/Smad 信号通路活化的影响。方法 将HSF分为对照组、模型组、圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组、SB⁃431542组。对照组不做任何处理，模型组用5.0 ng/mL TGF⁃β1干预24 h，圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组分别用40 μmol/L、80 μmol/L、160 μmol/L圣草酚和5.0 ng/mL TGF⁃β1同时干预24 h，SB⁃431542组用10 μmol/L SB⁃431542和5.0 ng/mL TGF⁃β1同时干预24 h。检测各组HSF细胞活力、α平滑肌肌动蛋白（α⁃SMA）蛋白表达水平、活性氧簇（ROS）含量、超氧化物歧化酶（SOD）活性，TGF⁃β1、α⁃SMA、Ⅰ型胶原蛋白（ColⅠ ）、Ⅲ型胶原蛋白（Col Ⅲ ）、基质金属蛋白酶2（MMP2） 的mRNA表达量及TGF⁃β1的蛋白表达水平。检测对照组、模型组、圣草酚中剂量组HSF的Smad2、Smad3、磷酸化Smad2 （p⁃Smad2）、磷酸化Smad3 （p⁃Smad3）蛋白表达水平。结果 与对照组相比，模型组的HSF细胞活力及α⁃SMA蛋白表达水平增加，ROS含量增加而SOD活性降低，TGF⁃β1、α⁃SMA、ColⅠ、Col Ⅲ和MMP2 mRNA表达量上调，TGF⁃β1、Smad2、Smad3、p⁃Smad2、p⁃Smad3的蛋白表达量亦上调（P<0.05）。与模型组相比，圣草酚各剂量组和SB⁃431542组HSF细胞活力降低、ROS含量降低、SOD活性增强，且α⁃SMA、ColⅠ、Col Ⅲ、MMP2的mRNA表达量和TGF⁃β1蛋白表达量下调，圣草酚中剂量组、圣草酚高剂量组和SB⁃431542组HSF细胞中α⁃SMA 蛋白表达水平降低，圣草酚中剂量组及SB⁃431542组Smad2、Smad3、p⁃Smad2、p⁃Smad3蛋白表达量下调（P<0.05）。圣草酚低剂量组、圣草酚中剂量组、圣草酚高剂量组HSF细胞活力、α⁃SMA 蛋白表达水平、ROS含量依次降低，SOD活性依次增强，α⁃SMA、ColⅠ、Col Ⅲ mRNA表达量依次降低（P<0.05）。结论 圣草酚可能通过抑制氧化应激反应及TGF⁃β1/Smad 通路的活化，从而剂量依赖性地抑制TGF⁃β1诱导的HSF细胞纤维化。
广西医学 页码：873-881
作者机构：张泆琳，在读硕士研究生，研究方向为中西医结合防治内科疾病。
基金信息：广西自然科学基金重点项目（2018GXNSFDA281047）；广西中医药重点学科建设项目（GZXK⁃Z⁃20⁃52）；广西研究生教育创新计划项目（YCSW2023213）
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Objective To explore the effect of eriodictyol on proliferation, oxidative stress response and TGF⁃β1/Smad signaling pathway activation of human skin fibroblasts (HSF) induced by transforming growth factor β1 (TGF⁃β1). Methods HSF was assigned to control group, model group, eriodictyol low⁃dose group, eriodictyol medium⁃dose group, eriodictyol high⁃dose group, or SB⁃431542 group. The control group did not received any treatment, whereas the model group received intervention for 24 hours with 5 ng/mL TGF⁃β1, and the eriodictyol low⁃, medium, and high⁃dose groups received intervention for 24 hours with 40 μmol/L, 80 μmol/L, and 160 μmol/L eriodictyol and 5.0 ng/mL TGF⁃β1 simultaneously, respectively; in addition, the SB⁃431542 group received intervention for 24 hours with 10 μmol/L SB⁃431542 and 5.0 ng/mL TGF⁃β1 simultaneously. The HSF cell activity, α⁃smooth muscle actin (α⁃SMA) protein expression, reactive oxygen species (ROS) content, superoxide dismutase (SOD) activity, and mRNA expressions of TGF⁃β1, α⁃SMA, collagen type Ⅰ (ColⅠ ), collagen type Ⅲ (Col Ⅲ ), matrix metalloproteinase 2 (MMP2), as well as TGF⁃β1 protein expression were detected in various groups. The protein expressions of Smad2, Smad3, phosphorylated Smad2 (p⁃Smad2), and phosphorylated Smad3 (p⁃Smad3) of HSF were detected in the control group, the model group, and the eriodictyol medium⁃dose group. Results Compared with the control group, the model group exhibited increased HSF cell activity and elevated α⁃SMA protein expression, increased ROS content while decreased SOD activity, up⁃regulated mRNA expressions of TGF⁃β1, α⁃SMA,ColⅠ , Col Ⅲ , and MMP2, and up⁃regulated protein expressions of TGF⁃β1, Smad2, Smad3, p⁃Smad2, and p⁃Smad3 (P<0.05). Compared with the model group, the eriodictyol various⁃dose groups and the SB⁃431542 group yielded decreased HSF cell activity, ROS content, while increased SOD activity, and down⁃regulated mRNA expressions of α⁃SMA, ColⅠ , Col Ⅲ , and MMP2, as well as down⁃regulated protein expression of TGF⁃β1; in addition, eriodictyol medium⁃ and high⁃dose groups and the SB⁃431542 group depicted decreased protein expression of α⁃SMA in HSF cell, and the eriodictyol medium⁃dose group and the SB⁃431542 group interpreted down⁃regulated protein expressions of Smad2, Smad3, p⁃Smad2, and p⁃Smad3 (P<0.05). The eriodictyol low⁃, medium⁃, and high⁃dose groups presented as decreased HSF cell activity, α⁃SMA protein expression, and ROS content successively, and increased SOD activity successively, as well as decreased mRNA expressions of α⁃SMA, ColⅠ , Col Ⅲ successively (P<0.05). Conclusion Eriodictyol may inhibit fibrosis of HSF cell induced by TGF⁃β1 in a dose⁃dependent manner by inhibiting oxidative stress response and the activation of TGF⁃β1/Smad pathway.
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