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+腹腔注射DHL[10 mg/(kg·d)]、UUO造模+腹腔注射等量溶剂、UUO造模+腹腔注射DHL[10 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collagenⅠ、collagenⅢ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。
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 andα-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 andα-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.
作者
黎忠大
王舒泓
谭宏伟
王晓
庄锦炀
申升
孙其鹏
Li Zhongda;Wang Shuhong;Tan Hongwei;Wang Xiao;Zhuang Jinyang;Shen Sheng;Sun Qipeng(Department of Organ transplantation,the Second People's Hospital of Guangdong Province,Affiliated to Jinan University,Guangzhou 510317,China;不详)
出处
《器官移植》
北大核心
2025年第5期763-770,共8页
Organ Transplantation
基金
广东省自然科学基金面上项目(2021A1515011379)。
