| 摘要: |
| [目的] 探讨当归芍药散是否通过调控Wnt/β-catenin改善肾纤维化，进而延缓DKD进展。[方法] 8只SPF级雄性db/m小鼠设为正常组，40只SPF级雄性db/db小鼠随机分为5组，每组8只，分别为模型组、厄贝沙坦组[0.025 g/（kg·d）]、当归芍药散低剂量组[16.77 g/（kg·d）]、当归芍药散中剂量组[33.54 g/（kg·d）]、当归芍药散高剂量组[67.08 g/（kg·d）]，正常组及模型组给予等体积生理盐水灌胃，均连续灌胃8周。研究期间，监测小鼠空腹血糖并记录小鼠的体质量。连续给药8周后，检测血肌酐（Scr）、尿素氮（BUN）、尿微量白蛋白（mALB）水平；HE、Masson、PAS染色观察肾脏病理变化及纤维化程度；Western blot、免疫组化（IHC）分别检测小鼠肾组织Ⅰ型胶原蛋白（CollagenⅠ）、上皮钙黏蛋白（E-Cadherin）、α-平滑肌肌动蛋白（α-SMA）、无翅型MMTV整合位点家族成员4（Wnt4）、β-连环蛋白（β-catenin）蛋白表达与定位；RT-qPCR检测小鼠肾组织中CollagenⅠ、E-Cadherin、α-SMA mRNA水平。[结果] 与正常组相比，模型组小鼠血糖、体质量、血肌酐、尿素氮、尿微量白蛋白表达增加，小鼠肾小球系膜基质显著增多，肾小管发生空泡变性且排列紊乱，同时肾间质存在炎性细胞浸润，胶原纤维条纹明显，肾组织中CollagenⅠ、α-SMA、Wnt4、β-catenin表达增加，E-Cadherin表达下降（P<0.01或P<0.05）。与模型组相比，各给药组小鼠状态较改善，血糖、体质量、血肌酐、尿素氮、尿微量白蛋白不同程度降低，肾组织损伤及纤维化有不同程度改善，肾组织中Collagen Ⅰ、α-SMA、Wnt4、β-catenin表达下降，E-Cadherin表达有所上升（P<0.01或P<0.05）。[结论] 当归芍药散可通过改善EMT，减少细胞外基质堆积，有效改善肾间质纤维化，其机制可能与抑制Wnt/β-catenin通路有关。 |
| 关键词: 当归芍药散 糖尿病肾脏病 肾间质纤维化 db/db小鼠 Wnt/β-catenin |
| DOI：10.11656/j.issn.1672-1519.2026.09.14 |
| 分类号:R285.5 |
| 基金项目:河北省自然科学基金项目（H2022423367）；河北省中医药管理局（2025285）；研究生创新资助立项项目（XCXZZSS2025028）。 |
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| Mechanistic study of Danggui Shaoyao San amelioration of renal fibrosis in db/db mice through the Wnt/β-catenin pathway |
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WANG Zixuan1, LI Ruijia1, GUO Shilong1, HOU Luyu1, SHI Wenjing1, QIANG Yitong2, GUO Dengzhou2
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1.Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050000, China;2.The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050011, China
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| Abstract: |
| [Objective] To investigate whether Danggui Shaoyao San（DSS）improves renal fibrosis by regulating the Wnt/β-catenin pathway，thereby delaying the progression of diabetic kidney disease（DKD）. [Methods] Eight SPF-grade male db/m mice served as the normal control group. Forty SPF-grade male db/db mice were randomly divided into five groups（n=8 each）：model group，irbesartan group [0.025 g/ （kg·d）]，low-dose Danggui Shaoyao San group [16.77 g/ （kg·d）]，medium-dose Danggui Shaoyao San group [33.54 g/ （kg·d）]， and high-dose Danggui Shaoyao San group [67.08 g/ （kg·d）]. The normal and model groups received equal volumes of saline via gastric gavage，with all groups receiving continuous gavage for 8 weeks. During the study period，fasting blood glucose levels were monitored and body weights were recorded. After 8 weeks of continuous administration，serum creatinine（Scr），blood urea nitrogen（BUN），and urinary microalbumin（mALB）levels were measured. Renal pathological changes and fibrosis severity were assessed using hematoxylin and eosin（HE），Masson’s trichrome，and periodic acid-Schiff（PAS）staining. Western blot and immunohistochemistry（IHC）were used to detect the expression and localization of Collagen I，E-Cadherin，α-SMA，Wnt4，and β-catenin proteins in renal tissues；real- time quantitative polymerase chain reaction（RT-qPCR）was employed to measure mRNA levels of Collagen I，E-Cadherin，and α-SMA in renal tissues. [Results] Compared with the normal group，the model group exhibited increased blood glucose，body weight，serum creatinine，blood urea nitrogen，and urinary microalbumin levels. The mesangial matrix in the glomeruli was significantly increased， tubules showed vacuolar degeneration and disorganized arrangement，and the renal interstitium demonstrated inflammatory cell infiltration with prominent collagen fiber striations. Expression of Collagen I，α-SMA，Wnt4，β-catenin increased，while E-cadherin expression decreased in renal tissue（P<0.01 or P<0.05）. Compared with the model group，all treatment groups showed improved conditions with varying degrees of reduction in blood glucose，body weight，serum creatinine，blood urea nitrogen，and urinary microalbumin. Renal tissue damage and fibrosis improved to varying extents，and renal tissue expression of collagen I，α-SMA，Wnt4，β-catenin decreased，while E-Cadherin expression increased（P<0.01 or P<0.05）. [Conclusion] Danggui Shaoyao San effectively ameliorates renal interstitial fibrosis by improving EMT and reducing extracellular matrix accumulation，potentially through inhibition of the Wnt/β-catenin pathway. |
| Key words: Danggui Shaoyao San diabetic kidney disease renal interstitial fibrosis db/db mice Wnt/β-catenin |
