| 杨勇琴.基于TGF-β1/Smad信号通路探讨地龙提取物蚓激酶对肾间质纤维化大鼠的肾脏保护作用[J].安徽医药,待发表. |
| 基于TGF-β1/Smad信号通路探讨地龙提取物蚓激酶对肾间质纤维化大鼠的肾脏保护作用 |
|
| 投稿时间：2025-05-06 录用日期：2025-06-03 |
| DOI： |
| 中文关键词: TGF-β1/Smad 蚓激酶 肾间质纤维化 大鼠 |
| 英文关键词: |
| 基金项目:楚雄医药高等专科学校科学研究基金项目（2023YYXM29）、云南中医药大学校院联合基金重点项目（XYLH202341） |
|
| 摘要点击次数: 107 |
| 全文下载次数: 0 |
| 中文摘要: |
| 目的：基于TGF-β1/Smad信号通路，探讨地龙提取物蚓激酶对肾间质纤维化大鼠肾脏的保护作用。方法：单侧输尿管结扎法制备肾间质纤维化大鼠模型。将SD大鼠分为假手术组、模型组、蚓激酶低、中、高剂量组和蚓激酶高剂量+SRI-011381组，每组10只。测定各组大鼠的血清肌酐（Scr）、血尿素氮（BUN）及24小时尿蛋白（24 h-Upro）水平，HE染色检测大鼠肾脏组织的病理学改变，Masson染色检测大鼠肾脏组织的胶原沉积情况，ELISA检测血清中IL-6、TNF-α的表达水平，Western blot检测肾脏组织中Ⅰ型胶原蛋白（collagen Ⅰ）和纤连蛋白（Fibronectin）、α-平滑肌肌动蛋白（α-SMA）、E-cadherin、N-cadherin、Vimentin、TGF-β1、p-Smad2/Smad2、p-Smad3/Smad3、Smad4、Smad7的表达。结果：相对于假手术组，模型组大鼠尿液中24 h-Upro水平及血清中Scr、BUN水平显著提升（P<0.05），肾组织可见病理学损伤及胶原纤维沉积，血清中IL-6、TNF-α的水平显著升高（P<0.05），肾组织中collagen Ⅰ、Fibronectin、N-cadherin、Vimentin、α-SMA、TGF-β1、p-Smad2/Smad2、p-Smad3/Smad3、Smad4蛋白的表达显著上调（P<0.05），E-cadherin、Smad7蛋白的表达显著下调（P<0.05）；相对于模型组，蚓激酶低、中、高剂量组大鼠尿液中24 h-Upro水平及血清中Scr、BUN水平显著降低（P<0.05），肾组织损伤及胶原纤维沉积减轻，血清中IL-6、TNF-α的水平显著降低（P<0.05），肾组织中collagen Ⅰ、Fibronectin、N-cadherin、Vimentin、α-SMA、TGF-β1、p-Smad2/Smad2、p-Smad3/Smad3、Smad4蛋白的表达显著下调（P<0.05），E-cadherin、Smad7蛋白的表达显著上调（P<0.05）；相对于蚓激酶高剂量组，蚓激酶高剂量+SRI-011381组大鼠的上述指标被显著逆转（P<0.05）。结论：本研究发现蚓激酶可通过减少过度的细胞外基质沉积、抑制炎症、抑制EMT对抗肾间质纤维化，其机制可能与抑制TGF-β1/Smad信号通路相关。 |
| 英文摘要: |
| Objective: Based on the TGF-β1/Smad signaling pathway, the protective effect of lumonkinase from dinosaur extract on the kidneys of rats with renal interstitial fibrosis. Methods: The rat model of renal interstitial fibrosis was prepared by unilateral ureteral ligation, and the experiment was divided into sham group, model group, lumbrokinase low, medium,high dose groups and high dose+SRI-011381 group, with 10 rats in each group. The serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour urine protein (24 h-Upro) levels were measured in each group. HE staining was used to detect the pathological changes of rat kidney tissue. Masson staining was used to detect collagen deposition in rat kidney tissue. ELISA was used to detect the expression levels of IL-6 and TNF-α in serum. The expression levels of type I collagen, fibronectin, α-smooth muscle actin (α-SMA), E-cadherin、N-cadherin、Vimentin、TGF-β1、p-Smad2/Smad2、p-Smad3/Smad3、Smad4、Smad7 in kidney tissue were detected by Western blot. Results: Compared with sham group, 24 h-Upro level in urine and Scr, BUN levels in serum of model group significantly increased (P<0.05), and pathological injury and collagen fiber deposition were observed in kidney tissue, and the levels of IL-6, TNF-α in serum significantly increased (P<0.05), and the expression levels of collagen Ⅰ, Fibronectin, N-cadherin, Vimentin, α-SMA, TGF-β1, p-Smad2/Smad2, p-Smad3/Smad3, Smad4 protein in kidney tissue significantly up-regulated (P<0.05), and the expression levels of E-cadherin, Smad7 protein significantly down-regulated (P<0.05). Compared with model group, 24 h-Upro level in urine and Scr, BUN levels in serum of lumbrokinase low, medium and high dose groups significantly decreased (P<0.05), and renal tissue damage and collagen fiber deposition reduced, and the levels of IL-6, TNF-α levels in serum significantly decreased (P<0.05), and the expression levels of collagen Ⅰ, Fibronectin, N-cadherin, Vimentin, α-SMA, TGF-β1, p-Smad2/Smad2, p-Smad3/Smad3, Smad4 protein in kidney tissue significantly down-regulated (P<0.05), and the expression levels of E-cadherin, Smad7 protein significantly up-regulated (P<0.05). Compared with the lumbrokinase high-dose group, the above indexes were significantly reversed in the lumbrokinase high-dose +SRI-011381 group (P<0.05). Conclusion: In this study, lumbrokinase reduces excessive extracellular matrix deposition, inhibit inflammation, and inhibit EMT against renal interstitial fibrosis, and its mechanism may be related to the inhibition of TGF-β1/Smad signaling pathway. |
|
查看/发表评论 下载PDF阅读器 |
| 关闭 |
|
|
|
