摘要: |
[目的] 探讨保肾通络方对于糖尿病肾病(DN)小鼠肾小球炎症及系膜基质增生的影响。[方法] KK-Ay小鼠高脂喂养4周建立DN小鼠模型。造模成功的KK-Ay小鼠随机分为模型组、保肾通络方组及缬沙坦组,另外选取C57BL/6J小鼠作为正常对照组。保肾通络方组予保肾通络方灌胃,缬沙坦组予缬沙坦灌胃,模型组及正常对照组予等剂量的蒸馏水灌胃。连续灌胃12周。在灌胃0、4、8和12周收集24 h尿液检测尿蛋白水平。灌胃12周后心尖取血检测血肌酐及尿素氮水平。苏木精-伊红(HE)、糖原(PAS)、Masson染色观察肾脏病理改变,免疫组化检测各组小鼠肾小球Ⅳ型胶原蛋白(Collagen Ⅳ)及纤连蛋白(FN)表达,逆转录-聚合酶链反应(RT-PCR)检测各组小鼠肾小球Collagen Ⅳ及FN的mRNA表达水平,酶联免疫法检测各组小鼠肾组织中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量。[结果] 与正常对照组相比,模型组小鼠24 h尿蛋白、血肌酐、血尿素氮水平明显升高(P<0.05);肾小球系膜细胞增多,细胞外基质增生;肾小球基质蛋白Collagen Ⅳ及FN蛋白和mRNA表达明显上调(P<0.05);肾组织TNF-α和IL-6水平明显升高(P<0.05)。与模型组相比,保肾通络方及缬沙坦组小鼠24 h尿蛋白、血肌酐、血尿素氮水平明显降低(P<0.05);肾小球系膜细胞增多及细胞外基质增生明显减轻;肾小球细胞外基质蛋白Collagen Ⅳ及FN蛋白和mRNA表达明显下调(P<0.05);肾组织TNF-α和IL-6水平明显下降(P<0.05)。[结论] 保肾通络方能够降低DN小鼠蛋白尿,改善肾功能,并且能够抑制肾小球炎症和系膜基质增生,减轻肾脏病理损伤。 |
关键词: 保肾通络方 糖尿病肾病 细胞外基质 Ⅳ型胶原蛋白 纤连蛋白 炎性因子 |
DOI:10.11656/j.issn.1672-1519.2023.11.16 |
分类号:R285.5 |
基金项目:国家自然科学基金项目(81703989);北京市自然科学基金资助项目(7222271);北京市属医院科研培育计划(PZ2019013);首都医科大学科研培育基金(自然类)(PYZ22163)。 |
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Mechanism research of Baoshen Tongluo Formula inhibition on inflammation and extracellular matrix accumulation of glomeruli to reduce kidney demage in DN mice |
CUI Fangqiang, WANG Yuefen, CAI Zhen, MENG Yuan, JIANG Xincan, ZHAO Wenjing
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Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
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Abstract: |
[Objective] To observe the effect of Baoshen Tongluo Formula(BSF) on inflammation and extracellular matrix accumulation of glomeruli in DN mice. [Methods] The model KK-Ay mice were separated into 3 groups randomly, DN group, XST group and BSF group. Ten C57 mice performed for NC group. Mice in BSF group were given BSF. Mice in XST group were given XST. Mice in DN and NC group were given distilled water. All mice were successive administration for 12 weeks. [Results] Compared with NC group, 24 h proteinuria, serum creatinine and urea nitrogen was significantly increased(P<0.05) and mesangial matrix was significantly accumulated in DN group. Compared with NC group, Collagen Ⅳ and FN expression was significantly increased in DN group(P<0.05). IL-6 and TNF-α was significantly increased in DN group(P<0.05). Compared with DN group, 24 h proteinuria, serum creatinine and urea nitrogen was significantly decreased(P<0.05) and mesangial matrix accumulation was significantly reversed in BSF group and XST group. Compared with DN group, Collagen Ⅳ and FN expression was significantly decreased in BSF group and XST group(P<0.05). IL-6 and TNF-α was significantly decreased in BSF group and XST group(P<0.05). [Conclusion] BSF can alleviate proteinuria and ameliorate renal function of DN, which partially through decreasing extracellular matrix accumulation and inflammation in DN. |
Key words: Baoshen Tongluo Formula diabetic nephropathy mesangial matrix Collagen Ⅳ fibronectin inflammation |