| 吴志全,杜斯斯,王延鑫,马江涛,贺泽威,宋伟波.银杏叶提取物调节TGF-β1/HGF信号通路对单侧输尿管梗阻小鼠肾纤维化的影响[J].,2024,(16):3039-3045 |
| 银杏叶提取物调节TGF-β1/HGF信号通路对单侧输尿管梗阻小鼠肾纤维化的影响 |
| Effects of Ginkgo Biloba Extract on Renal Fibrosis in Mice with Unilateral Ureteral Obstruction by Regulating TGF-β1/HGF Signaling Pathway |
| 投稿时间：2024-02-08 修订日期：2024-02-28 |
| DOI：10.13241/j.cnki.pmb.2024.16.007 |
| 中文关键词: 单侧输尿管梗阻 肾纤维化 银杏叶提取物 TGF-β1/HGF信号通路 炎症反应 |
| 英文关键词: Unilateral ureteral obstruction Renal fibrosis Ginkgo biloba extract TGF-β1/HGFsignaling pathway Inflammatory response |
| 基金项目:河北省中医药管理局科研计划项目（2020285）；石家庄市科技局科研计划项目（201460833） |
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| 中文摘要: |
| 摘要 目的：探究银杏叶提取物（GBE）调节转化生长因子β1（TGF-β1）/肝细胞生长因子（HGF）信号通路对单侧输尿管梗阻（UUO）小鼠肾纤维化的影响。方法：采用单侧输尿管结扎术法构建UUO小鼠模型，造模成功后将小鼠随机分为模型组、厄沙贝坦组（20 mg/kg）、GBE低、中、高剂量组（25 mg/kg、50 mg/kg、100 mg/kg），每组10只；另取10只小鼠为假手术组（仅分离左侧输尿管但不结扎）。检测肾功能指标：β-N-乙酰氨基葡萄糖苷酶（NAG）、肌酐（Scr）、尿素氮（BUN）；酶联免疫吸附试验（ELISA）法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平；苏木精-伊红（HE）染色观察肾脏组织病理变化；马森（Masson）染色观察肾脏组织纤维化情况；免疫组化法检测α-平滑肌肌动蛋白（α-SMA）、TGF-α1表达；Western blot检测肾脏组织Ⅰ型胶原（Col-Ⅰ）、α-SMA、TGF-β1、细胞信号转导分子2（Smad2）、磷酸化Smad2（p-Smad2）、HGF蛋白表达。结果：相比于假手术组，模型组小鼠肾脏组织肾小管腔扩张或萎缩，炎症细胞浸润，胶原纤维沉积明显，NAG、Scr、BUN、TNF-α、IL-1β、IL-6、肾纤维化水平、Col-Ⅰ、α-SMA、TGF-β1、p-Smad2/Smad2表达明显升高，HGF蛋白表达明显下降（P＜0.05）；相较于模型组，厄沙贝坦组和GBE低、中、高剂量组小鼠肾组织病理损伤减轻，胶原沉积纤维减少，NAG、Scr、BUN、TNF-α、IL-1β、IL-6、肾纤维化水平、Col-Ⅰ、α-SMA、TGF-β1、p-Smad2/Smad2表达明显降低，HGF蛋白表达明显升高（P＜0.05），其中厄沙贝坦组和EG高剂量组改善最为显著。结论：GBE能减轻肾功能损伤，抑制炎症反应，改善UUO小鼠的肾纤维化，其作用机制可能与调节TGF-β1/HGF信号通路平衡有关。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of ginkgo biloba extract (GBE) on renal fibrosis in mice with unilateral ureteral obstruction (UUO) by regulating transforming growth factor-β1 (TGF-β1)/hepatocyte growth factor (HGF) signaling pathway. Methods: The UUO mouse model was constructed by unilateral ureteral ligation, the mice were randomly divided into model group, irbesartan group (20 mg/kg), GBE low, medium and high dose groups (25 mg/kg, 50 mg/kg, 100 mg/kg) after successful modeling, with 10 mice in each group. Another 10 mice were taken as sham operation group (only the left ureter was separated but not ligated). Renal function indexes: β-N-acetylglucosaminidase (NAG), creatinine (Scr), urea nitrogen (BUN) were detected; The levels of serum tumor necrosis factor-α(TNF-α), interleukin (IL)-1β and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. The fibrosis of renal tissue were observed by masson (Masson) staining. The expressions of α-smooth muscle actin (α-SMA) and TGF-β1 were detected by immunohistochemistry. The expression of type I collagen (Col-I), α-SMA, TGF-β1, cell signal transduction molecule 2 (Smad2), phosphorylated Smad2 (p-Smad2) and HGF protein in renal tissue were detected by Western blot. Results: Compared with sham operation group, the renal tubular lumen in model group was dilated or atrophied, inflammatory cell infiltration, collagen fiber deposition was obvious, NAG, Scr, BUN, TNF-α, IL-1β, IL-6, renal fibrosis level, Col-I, α-SMA, TGF-β1, p-Smad2/Smad2 expression were significantly increased, and HGF protein expression was significantly decreased(P<0.05). Compared with model group, the pathological damage of renal tissue in irbesartan group and GBE low, medium and high dose groups was reduced, the collagen deposition fibers were reduced, NAG, Scr, BUN, TNF-α, IL-1β, IL-6, renal fibrosis level, Col-I, α-SMA, TGF-β1, p-Smad2/Smad2 expression were significantly decreased, and HGF protein expression was significantly increased(P<0.05), among which irbesartan group and EG high dose group improved most significantly. Conclusion: GBE can reduce renal function damage, inhibit inflammatory response, and improve renal fibrosis in UUO mice, the mechanism may be relate to regulating the balance of TGF-β1/HGF signaling pathway. |
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