| 林晓蒙,蔡旭东,钟光辉,等.温阳消癥方对5/6肾切除小鼠肾纤维化的保护作用及对TGF-β1/Smad3信号通路的影响[J].浙江中医药大学学报,2022,46(4):345-352, 387. |
| 温阳消癥方对5/6肾切除小鼠肾纤维化的保护作用及对TGF-β1/Smad3信号通路的影响 |
| Protective Effect of Wenyang Xiaozheng Decoction on Renal Fibrosis in 5/6 Nephrectomy Mice and Its Influence on TGF-β1/Smad3 Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2022.04.001 |
| 中文关键词: 温阳消癥方 肾纤维化 5/6肾切除 TGF-β1/Smad3信号通路 α-平滑肌肌动蛋白 纤维连接蛋白 |
| 英文关键词: Wenyang Xiaozheng Decoction renal fibrosis 5/6 nephrectomy TGF-β1/Smad3 signaling pathway α-smooth muscle actin fibronectin |
| 基金项目:浙江省自然科学基金项目(LY20H270004)；宁波市医疗卫生品牌学科项目(PPXK2018-07)；宁波市自然科学基金项目(2019A610265)；浙江省中医药科技计划项目(2020ZA102) |
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| 中文摘要: |
| [目的] 观察温阳消癥方对5/6肾切除小鼠肾功能、肾脏病理、纤维化指标及转化生长因子-β1(transforming growth factor-β1，TGF-β1)/Smad3通路的影响，探讨该方对肾纤维化的保护作用及可能的机制。[方法] 40只C57BL/6小鼠中随机选取10只作为假手术组，30只制作5/6肾切除模型，造模2周后测血清肌酐，确定造模成功，并将造模组随机分为温阳消癥组、缬沙坦组、模型组。温阳消癥组予温阳消癥方灌胃，缬沙坦组予缬沙坦灌胃，模型组与假手术组予等体积0.9%氯化钠注射液灌胃，给药8周后测定血清肌酐、尿素氮，苏木精-伊红(hematoxylin-eosin，HE)及Masson染色观察肾脏病理学改变，实时荧光定量聚合酶链式反应(Real-time fluorescence quantitative polymerase chain reaction，Real-time qPCR)和免疫印迹法检测肾组织α-平滑肌肌动蛋白(α-smooth muscle actin，α-SMA)、纤维连接蛋白(fibronectin，FN)、TGF-β1、Smad3的mRNA和蛋白表达。[结果] 与假手术组比较，模型组肾脏纤维化改变明显，血清肌酐、尿素氮、胶原染色阳性率及α-SMA、FN、TGF-β1、Smad3的mRNA和蛋白表达均显著升高(P＜0.01)。与模型组比较，温阳消癥组和缬沙坦组小鼠的肾脏病理纤维化形态改变较轻，血清肌酐、尿素氮、胶原染色阳性率，α-SMA、FN、TGF-β1的mRNA和蛋白表达，Smad3蛋白表达均显著降低(P＜0.01)；Smad3 mRNA表达降低(P＜0.01，P＜0.05)。与缬沙坦组比较，温阳消癥组的α-SMA mRNA和蛋白表达，以及TGF-β1 mRNA表达显著降低(P＜0.01)；胶原染色阳性率和FN mRNA表达降低(P＜0.05)。[结论] 温阳消癥方可改善5/6肾切除小鼠肾功能，减轻病理改变，下调肾纤维化标志物α-SMA及FN的表达，减轻细胞外基质(extracellular matrix，ECM)异常堆积，其机制可能与抑制TGF-β1/Smad3信号通路有关。 |
| 英文摘要: |
| [Objective] To observe the effects of Wenyang Xiaozheng Decoction on renal function， renal pathology， fibrosis index and transforming growth factor-β1(TGF-β1)/Smad3 signaling pathway in 5/6 nephrectomy mice， and to explore the protective effect and possible mechanism of Wenyang Xiaozheng Decoction on renal fibrosis. [Methods] Ten of 40 C57BL/6 mice were randomly selected as sham operation group， and 30 mice were made 5/6 nephrectomy models. After 2 weeks， serum creatinine was measured to confirm that the model construction was successful. The model was randomly divided into Wenyang Xiaozheng group， valsartan group and model group. Wenyang Xiaozheng group was given Wenyang Xiaozheng Decoction， valsartan group was given valsartan， model group and sham operation group were given equal volume of 0.9% sodium chloride injection. Eight weeks after administration， serum creatinine and urea nitrogen were measured， hematoxylin-eosin(HE) staining and Masson staining were used to observe renal pathology， and Real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR) and Western blot were used to detect the expressions of mRNA and protein of α-smooth muscle actin(α-SMA)， fibronectin(FN)， TGF-β1， Smad3 in renal tissue. [Results] Compared with sham operation group， the pathological fibrosis of the kidney was significantly changed in model group， and the serum creatinine， urea nitrogen， and the positive rates of collagen staining as well as the mRNA and protein expressions of α-SMA， FN， TGF-β1 and Smad3 were all significantly increased(P＜0.01). Compared with model group， the renal pathological changes in Wenyang Xiaozheng group and valsartan group were slighter， the serum creatinine and urea nitrogen， the positive rate of collagen staining， the mRNA and protein expressions of α-SMA， FN， TGF-β1， the protein expression of Smad3 were significantly lower(P＜0.01)， and the mRNA expression of Smad3 was lower(P＜0.01， P＜0.05). Compared with valsartan group， the expressions of α-SMA mRNA and protein， and TGF-β1 mRNA in Wenyang Xiaozheng group were decreased significantly(P＜0.01); the positive rate of collagen staining and the mRNA expression of FN were decreased(P＜0.05). [Conclusion] Wenyang Xiaozheng Decoction can improve the renal function of 5/6 nephrectomy mice， reduce the pathological changes， down-regulate the mRNA and proteins expressions of α-SMA and FN of renal fibrosis markers， and reduce the abnormal accumulation of extracellular matrix(ECM)， which may be related to the inhibition of TGF-β1/Smad3 signaling pathway. |
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