去氢木香烃内酯通过抑制TGF-β1/Smad2/3通路改善单侧输尿管梗阻大鼠肾间质纤维化

Dehydrocostus lactone ameliorates renal interstitial fibrosis in rats with unilateral ureteral obstruction by inhibiting the TGF-β1/Smad2/3 pathway

  • 摘要:
    目的  探讨去氢木香烃内酯(DHL)对单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的作用机制。
    方法  将44只雄性SD大鼠随机分为假手术组(Sham组)、单纯药物干预组(Sham+DHL组)、实验组(UUO+Vehicle组)和DHL治疗组(UUO+DHL组),每组11只,分别进行假手术、假手术+DHL10 mg/(kg·d)、UUO造模+等量溶剂、UUO造模+DHL10 mg/(kg·d),手术造模2 d后连续用DHL或等量溶剂灌胃14 d。通过苏木素-伊红(HE)和Masson染色观察大鼠肾组织病理学改变;免疫组织化学染色检测collagen Ⅰ、collagen Ⅲ及α-平滑肌肌动蛋白(α-SMA)表达水平;蛋白质印迹法检测转化生长因子(TGF)-β1/Smad2/3通路蛋白水平。
    结果 与UUO+Vehicle组比较,DHL治疗缓解大鼠肾间质病理损伤,减少胶原纤维沉积以及collagen I、collagen III、α-SMA表达,同时抑制TGF-β1和Smad2/3蛋白的表达。
    结论  DHL通过抑制TGF-β1/Smad2/3通路减轻大鼠RIF,为慢性肾病的治疗提供新策略。

     

    Abstract:
    Objective  To explore the action mechanism of dehydrocostus lactone (DHL) on renal interstitial fibrosis (RIF) in rats with unilateral ureteral obstruction (UUO).
    Methods  Forty-four male SD rats were randomly divided into four groups: the sham surgery group (Sham group), the pure drug intervention group (Sham+DHL group), the experimental group (UUO+Vehicle group), and the DHL treatment group (UUO+DHL group), with 11 rats in each group. The rats underwent sham surgery, sham surgery + DHL 10 mg/(kg·d), UUO modeling + the same volume of solvent, and UUO modeling + DHL 10 mg/(kg·d), respectively. After surgery, DHL or the same volume of solvent was administered by gavage for 14 days starting from day 2 post-surgery. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes in renal tissue. Immunohistochemical staining was performed to detect the expression levels of collagen I, collagen III, and α-smooth muscle actin (α-SMA). Western blotting was used to detect the protein levels of the transforming growth factor (TGF)-β1/Smad2/3 pathway.
    Results  Compared with the UUO+Vehicle group, DHL treatment alleviated renal interstitial pathological damage, reduced collagen fiber deposition, and decreased the expression of collagen I, collagen III, and α-SMA. It also inhibited the expression of TGF-β1 and Smad2/3 proteins.
    Conclusions DHL mitigates RIF in rats by inhibiting the TGF-β1/Smad2/3 pathway, providing a new strategy for the treatment of chronic kidney disease.

     

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