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李琰,刘佑晖,蔡虎志,陈新宇.温阳振衰颗粒对慢性肾衰竭大鼠TGF-β1/Smad/MMP-2信号通路的影响[J].湖南中医药大学学报英文版,2022,42(12):1995-2001.[Click to copy
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| 温阳振衰颗粒对慢性肾衰竭大鼠TGF-β1/Smad/MMP-2信号通路的影响 |
| 李琰,刘佑晖,蔡虎志,陈新宇 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 通过研究温阳振衰颗粒对多柔比星诱导的慢性肾衰竭大鼠转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Sma和Mad相关蛋白(Sma-and Mad-related protein, Smad)/基质金属蛋白酶-2(matrix metalloproteinase-2, MMP-2)信号通路的影响,结合肾脏组织病理学、临床血尿生化指标,探讨温阳振衰颗粒对慢性肾衰竭的作用机制。方法 选取SPF级雄性大鼠57只,随机分为正常对照组(15只)和实验组(42只)。第4、第18天,实验组尾静脉注射多柔比星4 mg/kg进行造模。实验组造模成功后随机分为模型对照组、缬沙坦组、温阳振衰组,每组14只。予相应药物或蒸馏水灌胃,每天1次,干预12周。干预后,检测24 h尿蛋白(24 h urine protein, 24 h Upro)、血肌酐(serum creatinine, Scr)、血尿素氮(blood urea nitrogen, BUN),光学显微镜观察肾脏组织形态学改变,采用Western blot检测肾脏组织中TGF-β1、Smad3、Smad7、MMP-2、组织金属蛋白酶抑制物-2(tissue inhibitor of metalloproteinase-2, TIMP-2)的表达。结果 与正常对照组比较,模型对照组24 h Upro、Scr、BUN、TGF-β1、Smad3、MMP-2、TIMP-2均明显升高(P<0.05),Smad7明显降低(P<0.05)。与模型对照组比较,温阳振衰组和缬沙坦组24 h Upro、Scr、BUN、TGF-β1、Smad3、TIMP-2均明显降低(P<0.05),Smad7、MMP-2均显著升高(P<0.05)。结论 温阳振衰颗粒能有效降低慢性肾衰竭大鼠24 h Upro、Scr、BUN,下调TGF-β1、Smad3、TIMP-2的表达,上调Smad7、MMP-2的表达,并改善肾脏组织形态学变化,减少炎性细胞的浸润和纤维化的发生,延缓慢性病理进展。 |
| 关键词: 慢性肾衰竭 多柔比星 温阳振衰颗粒 转化生长因子-β1 Smad3 组织金属蛋白酶抑制物-2 |
| DOI：10.3969/j.issn.1674-070X.2022.12.007 |
| Received:September 07, 2022 |
| 基金项目:湖南省教育厅科学研究项目(20C1412); 湖南省研究生科研创新项目(CX2018B474); 全国名老中医药专家陈新宇传承工作室建设项目(国中医药人教函[2022]75号) |
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| Effects of Wenyang Zhenshuai Granule on the expression of TGF-β1/Smad/MMP-2 signal pathways in the rats model of chronic renal failure |
| LI Yan,LIU Youhui,CAI Huzhi,CHEN Xinyu |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the pharmacological mechanism of Wenyang Zhenshuai Granule on chronic renal failure by studying its influence on the expression of transforming growth factor-β1(TGF-β1)/Sma-and Mad-related protein(Smad)/matrix metalloproteinase 2(MMP-2) signal pathways of the renal tissue in chronic renal failure rat models induced by adriamycin.Histopathology, urinary protein and serum biochemical indexes were measured to support the study.Methods A total of 57 SPF male rats were randomly selected and divided into normal group(n=15) and experimental group(n=42). The experimental models were developed by injecting adriamycin 4 mg/kg into tail-vein on the 4th and 18th day. As soon as the experimental models were successfully developed, experimental group was randomly divided into model control group(n=14), valsartan group(n=14) and Wenyang Zhenshuai group(n=14). Each group was given corresponding drugs or distilled water by intragastric administration, once a day, for 12 weeks. After intervention, 24 h urine protein(24 h Upro), serum creatinine(Scr) and blood ureanitrogen(BUN) were detected,and the histomorphologic changes of kidney were observed by optical microscope. The expression levels of TGF-β1, Smad3, Smad7,MMP-2 and tissue inhibitors of matrix metalloproteinase-2(TIMP-2) were detected by Western blot.Results Compared with normal control group, 24 h Upro, Scr, BUN, TGF-β1, Smad3, MMP-2 and TIMP-2 increased significantly in model control group(P<0.05),while Smad7 remarkably decreased(P<0.05). Compared with model control group, 24 h Upro, Scr, BUN, TGF-β1, Smad3 and TIMP-2 in Wenyang Zhenshuai Granule group and valsartan group decreased significantly(P<0.05), and Smad7 obviously increased(P<0.05).Conclusion Wenyang Zhenshuai Granule can effectively reduce the 24 h Upro, Scr, BUN in rat model of chronic renal failure,down-regulate the expression levels of TGF-β1, Smad3, and TIMP-2, and up-regulate the expression levels of Smad7 and MMP-2.It also helps to improve the histopathological changes of kidney tissue and to delay the pathological progression of disease by reducing inflammatory cell infiltration and fibrosis. |
| Key words: chronic renal failure adriamycin Wenyang Zhenshuai Granule transforming growth factor-β1 Smad3 tissue inhibitor of metalloproteinase-2 |
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