三叶香茶菜介导 IκB-α 磷酸化对 CCl4 致大鼠肝纤维化的影响
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作者单位:

1.广西医科大学附属柳州市人民医院,广西 柳州 545006;2.右江民族医学院,广西 百色 533000; 3.广西中医药大学,南宁 530001

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R-33


Isodon ternifolius (D. Don) Kudo alleviates carbon tetrachloride-induced liver fibrosis in rats by downregulating IκB-α phosphorylation
Author:
Affiliation:

1. Liuzhou People’s Hospital of Guangxi Medical University, Liuzhou 545006, China. 2. Youjiang Medical University for Nationalities, Baise 533000. 3. Guangxi University of Chinese Medicine, Nanning 530001

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    摘要:

    目的 探讨三叶香茶菜通过影响 IκB-α 及其磷酸化下调核转录因子( nuclear transcription factor-κB, NF-κB)信号通路减轻四氯化碳诱导大鼠肝纤维化。 方法 采用 CCl4 肝纤维化大鼠模型,生化检测血清中谷丙转 氨酶(ALT)、羟脯氨酸(HYP),ELISA 检测转化生长因子 β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)水平、白介素-6 (IL-6)、肿瘤坏死因子-α( TNF-α),荧光定量 PCR 法检测大鼠肝组织 Toll 样受体 4 ( TLR4) mRNA、NF-κB p65 mRNA、NF-κB 抑制蛋白-α(IκB-α)mRNA 的表达,Western blot 法检测大鼠肝组织中 TLR4、NF-κB p65、p-IκB-α 蛋白表达,HE 染色评价肝组织病理损害。 结果 与模型组相比较,三叶香茶菜能够显著抑制肝纤维化大鼠中 ALT、 HYP、TGF-β1、α-SMA、IL-6、TNF-α 水平,改善大鼠肝组织病理损害,显著抑制肝纤维化大鼠 TLR4 mRNA、NF-κB p65 mRNA 的表达,上调 IκB-α mRNA 的表达,下调 TLR4、NF-κB p65 蛋白表达,下调 p-IκB-α 蛋白的表达。 结论 三叶香茶菜下调IκB-α 磷酸化,抑制 NF-κB 信号通路的活化,达到抗肝慢性炎症损伤作用。

    Abstract:

    Objective To investigate whether the Isodon ternifolius ( D. Don ) Kudo attenuates carbon tetrachloride (CCl4 )-induced liver fibrosis in rats by downregulating the nuclear transcription factor-κB (NF-κB) signaling pathway through interference with IκB-α phosphorylation. Methods Hepatic fibrosis was induced in rats with CCl4 . Biochemical analysis was used to detect alanine aminotransferase (ALT) and hydroxyproline ( HYP), and the enzyme- linked immunosorbent assay was used to detect transforming growth factor (TGF-β1), α-smooth muscle actin (α-SMA), interleukin-6 (IL-6) and tumor necrosis factor-α ( TNF-α) levels in sera. Fluorescence quantitative PCR was used to detect Toll-like receptor 4 (TLR4), NF-κB p65, IκB-α mRNA expression, and Western blot were used to analyze TLR4, NF-κB p65, and phosphorylated (p)-IκB-α protein expression in rat liver tissues. Hematoxylin-eosin staining was used to evaluate histopathological damage in the rat livers. Results Compared with that in the model group, the pathological damage to the livers of rats treated with Isodon ternifolius (D. Don) Kudo extracts was ameliorated; the levels of ALT, HYP, TGF-β1, α-SMA, IL-6 and TNF-α in the serum of rats with liver fibrosis treated with Isodon ternifolius (D. Don) Kudo extracts were significantly reduced; the expression of TLR4 and NF-κB p65 mRNA were significantly inhibited; IκB- α mRNA was significantly upregulated; and the expression of TLR4, NF-κB p65 and p-IκB-α protein was downregulated. Conclusions Isodon ternifolius (D. Don) Kudon alleviated liver fibrosis by downregulating IκB-α phosphorylation and inhibiting activation of the NF-κB signaling pathway.

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周至品,农汝楠,覃 乐,刘代华,王竟静,陈 勇,王晓源.三叶香茶菜介导 IκB-α 磷酸化对 CCl4 致大鼠肝纤维化的影响[J].中国比较医学杂志,2022,32(2):10~15.

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  • 收稿日期:2021-04-25
  • 在线发布日期: 2022-04-12
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