甘林望, 张丽玲, 黄焱, 高利超, 耿蕾. 姜黄素调控TGF-β1/Smad信号通路改善大鼠腹膜透析相关腹膜纤维化及机制研究[J]. 临床肾脏病杂志, 2023, 23(2): 129-135. DOI: 10.3969/j.issn.1671-2390.2023.02.008
    引用本文: 甘林望, 张丽玲, 黄焱, 高利超, 耿蕾. 姜黄素调控TGF-β1/Smad信号通路改善大鼠腹膜透析相关腹膜纤维化及机制研究[J]. 临床肾脏病杂志, 2023, 23(2): 129-135. DOI: 10.3969/j.issn.1671-2390.2023.02.008
    Gan Lin-wang, Zhang Li-ling, Huang Yan, Gao Li-chao, Geng Lei. Curcumin regulated TGF-β1/Smad signaling pathway for improving peritoneal fibrosis related to peritoneal dialysis in rats and understanding its mechanism[J]. Journal of Clinical Nephrology, 2023, 23(2): 129-135. DOI: 10.3969/j.issn.1671-2390.2023.02.008
    Citation: Gan Lin-wang, Zhang Li-ling, Huang Yan, Gao Li-chao, Geng Lei. Curcumin regulated TGF-β1/Smad signaling pathway for improving peritoneal fibrosis related to peritoneal dialysis in rats and understanding its mechanism[J]. Journal of Clinical Nephrology, 2023, 23(2): 129-135. DOI: 10.3969/j.issn.1671-2390.2023.02.008

    姜黄素调控TGF-β1/Smad信号通路改善大鼠腹膜透析相关腹膜纤维化及机制研究

    Curcumin regulated TGF-β1/Smad signaling pathway for improving peritoneal fibrosis related to peritoneal dialysis in rats and understanding its mechanism

    • 摘要: 目的 探讨姜黄素对大鼠腹膜透析(peritoneal dialysis,PD)相关腹膜纤维化(peritoneal fibrosis,PF)的影响及可能作用机制。方法 随机选取10只雄性Wistar大鼠作为正常组(生理盐水),剩余大鼠随机分为模型组(生理盐水)及姜黄素低(15 mg·kg-1·d-1)、中(30 mg·kg-1·d-1)、高(60 mg·kg-1·d-1)剂量组,每组各10只,给药同时腹腔内注射4.25%葡萄糖PD溶液(100 mL/kg),连续30 d。4 h腹膜平衡试验评估腹膜功能;测量腹膜厚度;腹膜组织行HE和Masson染色观察腹膜病理变化;ELISA法检测腹膜组织肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)及白细胞介素1β(interleukin-1β,IL-1β)水平;蛋白质印迹法检测腹膜组织中转化生长因子-β1(transforming growth factor-β1,TGF-β1)、Smad2/3、p-Smad2/3、Smad7、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原蛋白(collagen Ⅰ,Col Ⅰ)蛋白相对表达情况。结果 与正常组比较,模型组大鼠腹膜超滤体积降低,葡萄糖转运量升高,腹膜厚度增加(P<0.05),结构紊乱、间皮细胞变形、炎症细胞严重浸润、胶原蛋白严重沉积;腹膜组织中TNF-α、IL-6、IL-1β水平升高,TGF-β1、p-Smad2/3、α-SMA及Col Ⅰ蛋白相对表达水平升高,Smad7蛋白相对表达水平降低(P<0.05);与模型组比较,姜黄素低、中、高剂量组大鼠腹膜组织超滤体积升高,葡萄糖转运量降低,腹膜厚度减少(P<0.05),结构逐渐完整,炎症浸润及胶原蛋白沉积情况有所减轻;腹膜组织中TNF-α、IL-6、IL-1β水平降低,TGF-β1、p-Smad2/3、α-SMA及Col Ⅰ蛋白相对表达水平降低,Smad7蛋白相对表达水平升高(P<0.05);姜黄素改善PD相关PF大鼠的效果呈剂量依赖性作用。结论 姜黄素可减轻PD相关PF大鼠腹膜组织病理损伤,改善腹膜功能障碍,其作用机制可能与减轻炎性反应,阻滞TGF-β1/Smad信号通路激活,进而抑制PF发生、发展有关。

       

      Abstract: Objective To explore the effect of curcumin on peritoneal fibrosis(PF) associated with peritoneal dialysis(PD) in rats and elucidate its possible mechanism.Methods Ten male Wistar rats were selected as normal group(normal saline) while the remaining rats were randomly divided into model group(normal saline), curcumin low-dose(15 mg·kg-1·d-1), medium-dose(30 mg·kg-1·d-1) and high-dose(60 mg·kg-1·d-1) groups(n=10 each).At the same time, 4.25% glucose PD solution(100 mL/kg) was intraperitoneally injected for 30 consecutive days.And 4h peritoneal balance test was performed for evaluating peritoneal function.Peritoneal thickness was measured.Hematoxylin-eosin(HE) and Masson stains were performed for observing the pathological changes of peritoneum.The levels of tumor necrosis factor-α(TNF-α), interleukin 6(IL-6) and interleukin 1β(IL-1β) in peritoneal tissue were determined by enzyme-linked immunosorbent assay(ELISA).Western blot was employed for detecting the relative expressions of transforming growth factor -β1(TGF-β1), Smad2/3, p-Smad2/3, Smad7, α-smooth muscle actin(α-SMA) and type Ⅰ collagen(Col Ⅰ) proteins in peritoneal tissues.Results As compared with normal group, peritoneal ultrafiltration volume(UFV) of model group declined, glucose transfer volume(MTG) expanded and peritoneal thickness increased(P<0.05).There were structural disarray, deformation of mesenchymal cell, infiltration of inflammatory cell and collagen deposition.In peritoneal tissues, the levels of TNF-α, IL-6 and IL-1β spiked, the relative expression levels of TGF-β1, p-Smad2/3, α-SMA and Col Ⅰ protein jumped and the relative expression level of Smad7 white declined(P<0.05).As compared with model group, peritoneal tissue UFV rose, MTG and peritoneal thickness declined(P<0.05) and structure grew gradually more intact, inflammatory infiltration and collagen deposition declined in curcumin low/medium/high-dose group.The levels of TNF-α, IL-6 and IL-1β declined, the relative expression levels of TGF-β1, p-Smad2/3, α-SMA and Col Ⅰdropped and the relative expression level of Smad7 white rose(P<0.05).The effect of curcumin on PD-related PF rats was dose-dependent.Conclusions Curcumin could alleviate peritoneal histopathological injury and improve peritoneal dysfunction in PD-related PF rats, and its mechanism may be related to alleviating inflammatory response, blocking the activation of TGF-β1/Smad signaling pathway, and then inhibiting the occurrence and development of PF.

       

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