Department of Chinese Medicine/Department of Chinese Integrative Medicine, The First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
3 Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Chinese Medicine, Shanghai 200062, China.
J Tradit Chin Med. 2022 Oct;42(5):723-731. doi: 10.19852/j.cnki.jtcm.2022.05.006.
To investigate the effect of Huangqi decoction on renal interstitial fibrosis and its association with the transforming growth factor-β1 (TGF-β1) / mitogen-activated protein kinase (MAPK) signaling pathway.
120 C57/BL mice were randomly divided into six groups: sham group, Enalapril (20 mg/kg) group, 5/6 nephrectomy model group, and 5/6 nephrectomy model plus Huangqicoction (0.12, 0.36 and 1.08 g/kg respectively) groups. Detecting 24hours urinary protein, blood pressure, serum creatinine, urea nitrogen content changes. Periodic Acid-Schiff stain (PAS) and Masson's trichrome staining was used to observe the renal tissue pathological changes. Protein expression of TGF-β1, Phosphorylated P38 mitogen activated protein kinases (P-P38), Phosphorylated c-jun N-terminal kinase (P-JNK), Phosphorylated extracellular regulated proteinhnase (P-ERK), Fibroblast-specific protein-1 (FSP-1), Alpha smooth muscle actin (α-SMA), Type III collagen (Collagen III), Connective tissue growth factor (CTGF), Bcl-2 Assaciated X protein (Bax) and B cell lymphoma 2 (Bcl-2) were measured with western blot and immunohistochemical.
Both Huangqi decoction and Enalapril improved the kidney function, 24 h urinary protein and the fibrosis in 5/6 nephrectomy mice, Huangqi decoction downregulated the expressions of TGF-β1, FSP-1, α-SMA, Collagen III and CTGF in a dose-dependent manner, and it has a significant difference ( 0.01) compared with model group.Huangqi decoction downregulated the expressions of P-P38, P-JNK, P-ERK and Bcl-2 in a dose-dependent manner, while upregulated the expression of Bax.
The protective effect of Huangqi decoction for renal interstitial fibrosis in 5/6 nep-hrectomized mice the inhibition of Epithelial-Mesenchymal Transitions and downregulating the TGF-β1/ MAPK signaling pathway.
探讨黄芪汤对肾间质纤维化的影响及其与转化生长因子-β1（TGF-β1）/丝裂原活化蛋白激酶（MAPK）信号通路的关系。
将 120 只 C57/BL 小鼠随机分为六组：假手术组、依那普利（20mg/kg）组、5/6 肾切除模型组及 5/6 肾切除模型加黄芪汤（0.12、0.36 和 1.08g/kg）组。检测 24 小时尿蛋白、血压、血肌酐、尿素氮含量变化。过碘酸希夫染色（PAS）和 Masson 三色染色观察肾组织病理变化。Western blot 和免疫组化法检测 TGF-β1、磷酸化 P38 丝裂原活化蛋白激酶（P-P38）、磷酸化 c-jun N 末端激酶（P-JNK）、磷酸化细胞外调节蛋白激酶（P-ERK）、成纤维细胞特异性蛋白-1（FSP-1）、α平滑肌肌动蛋白（α-SMA）、III 型胶原（Collagen III）、结缔组织生长因子（CTGF）、B 细胞淋巴瘤 2 相关 X 蛋白（Bax）和 B 细胞淋巴瘤 2（Bcl-2）的蛋白表达。
黄芪汤和依那普利均改善了 5/6 肾切除小鼠的肾功能、24 小时尿蛋白和纤维化，黄芪汤呈剂量依赖性下调 TGF-β1、FSP-1、α-SMA、Collagen III 和 CTGF 的表达，与模型组比较差异有统计学意义（P<0.01）。黄芪汤呈剂量依赖性下调 P-P38、P-JNK、P-ERK 和 Bcl-2 的表达，同时上调 Bax 的表达。
黄芪汤对 5/6 肾切除小鼠肾间质纤维化具有保护作用，其机制可能与抑制上皮间质转化及下调 TGF-β1/MAPK 信号通路有关。
