Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
J Ethnopharmacol. 2019 Mar 1;231:302-310. doi: 10.1016/j.jep.2018.10.023. Epub 2018 Oct 18.
Ribes diacanthum Pall (RDP), a folk medicine, has been widely used in Mongolia to treat urinary system diseases.
To investigate the effectiveness of RDP on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis and the underlying mechanisms.
A total of 60 mice were randomly divided into six groups: sham group, sham plus RDP (40 mg/kg) group, UUO model group, and UUO model plus RDP (10, 20 or 40 mg/kg) groups. After surgery, aqueous extract of RDP were administrated intragastrically (i.g) daily for a week and ipsilateral kidneys were collected seven days after surgery. Levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were detected to reflect the kidney injury. Hematoxylin & eosin and Masson's trichrome staining were used to evaluate the kidney morphological changes and fibrosis, respectively. ELISA was used to examine the levels of pro-inflammatory cytokines. Immunohistochemistry, western blot and PCR were used to examine the expression levels of key proteins involved in transforming growth factor (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways.
RDP treatment attenuates the level of BUN and kidney fibrosis in UUO mice, decreases the expressions of interleukin-6, tumor necrosis factor-α, Interleukin-1α, TGF-β1, monocyte chemotactic protein-1, α-smooth muscle actin, collagen I, fibronectin, and vimentin, while increases the expressions of E-cadherin and hepatocyte growth factor. Moreover, RDP administration significantly decreases the levels of p-Smad2/3, p-ERK1/2, p-p38 and p-JNK, while increases the expression level of Smad7 in UUO models.
These data demonstrate that RDP ameliorates renal fibrosis through TGF-β/Smad and MAPK pathways in a UUO mouse model.
黑穗醋栗（Ribes diacanthum Pall，RDP），一种民间药物，在蒙古被广泛用于治疗泌尿系统疾病。
研究 RDP 对单侧输尿管梗阻（UUO）诱导的肾间质纤维化的作用及其机制。
将 60 只小鼠随机分为 6 组：假手术组、假手术加 RDP（40mg/kg）组、UUO 模型组和 UUO 模型加 RDP（10、20 或 40mg/kg）组。手术后，RDP 的水提物通过灌胃（i.g）每天给药 1 周，手术后 7 天收集同侧肾脏。检测血尿素氮（BUN）和血清肌酐（Scr）水平以反映肾损伤。苏木精和伊红（H&E）及 Masson 三色染色分别用于评估肾脏形态变化和纤维化程度。ELISA 用于检测促炎细胞因子水平。免疫组织化学、Western blot 和 PCR 用于检测转化生长因子（TGF-β）/Smad 和丝裂原活化蛋白激酶（MAPK）信号通路相关关键蛋白的表达水平。
RDP 治疗可减轻 UUO 小鼠的 BUN 水平和肾纤维化程度，降低白细胞介素-6、肿瘤坏死因子-α、白细胞介素-1α、TGF-β1、单核细胞趋化蛋白-1、α-平滑肌肌动蛋白、I 型胶原、纤维连接蛋白和波形蛋白的表达水平，同时增加 E-钙黏蛋白和肝细胞生长因子的表达水平。此外，RDP 给药可显著降低 UUO 模型中 p-Smad2/3、p-ERK1/2、p-p38 和 p-JNK 的水平，同时增加 Smad7 的表达水平。
这些数据表明，RDP 通过 TGF-β/Smad 和 MAPK 通路改善 UUO 小鼠模型的肾纤维化。
