Department of Nephrology, the Second Affiliated Hospital of Shantou University Medical College, 515041, Shantou, China.
Curr Mol Med. 2024;24(12):1540-1549. doi: 10.2174/0115665240264823231101103226.
To explore a new approach for the treatment of renal interstitial fibrosis (RIF), we detected the expression of matrix metalloproteinase-9 (MMP9) and vascular endothelial growth factor (VEGF).
Twenty-four male Sprague Dawley (SD) rats were randomly divided into 2- week normal control (2NC) group, 4-week NC (4NC) group, 2-week unilateral ureteral obstruction (2UUO) group, and 4-week UUO (4UUO) group. We performed left ureteral ligation on UUO groups. Then, we sacrificed the rats of the 2NC group and 2UUO group at 2 weeks and the other groups at 4 weeks after the surgery. Immunohistochemistry and western blot were applied to detect the expression of MMP9, VEGF, fibronectin (FN), type IV collagen (Col-IV), and transforming growth factor-β1 (TGF-β1). MMP9 levels reduced after UUO surgery. Its expression was less in the 4UUO group than in the 2UUO group (P<0.05). The expression of VEGF, TGF- β1, FN, and Col-IV was higher in UUO groups than in NC groups (P<0.05). The expression of these indicators was higher in the 4UUO group than in the 2UUO group (P<0.05).
In the correlation analysis, MMP9 levels in UUO groups had a negative correlation with the expression of TGF-β1, VEGF, Col-IV, FN, and RIF index (all P<0.05). In UUO groups, VEGF levels had a positive correlation with the expression of TGF-β1, Col-IV, FN, and RIF index (all P<0.05).
In conclusion, with the aggravation of RIF lesions, MMP9 levels decreased, and VEGF levels increased. Whether there is a mutual inhibition relationship between them remains to be confirmed by further experiments.
探讨治疗肾间质纤维化（RIF）的新方法，检测基质金属蛋白酶-9（MMP9）和血管内皮生长因子（VEGF）的表达。
24 只雄性 Sprague Dawley（SD）大鼠随机分为 2 周正常对照组（2NC 组）、4 周对照组（4NC 组）、2 周单侧输尿管梗阻（2UUO 组）和 4 周单侧输尿管梗阻（4UUO 组）。UUO 组行左侧输尿管结扎术。然后，2NC 组和 2UUO 组大鼠分别于术后 2 周，其他各组大鼠于术后 4 周处死。采用免疫组化法和 Western blot 法检测 MMP9、VEGF、纤维连接蛋白（FN）、IV 型胶原（Col-IV）和转化生长因子-β1（TGF-β1）的表达。UUO 术后 MMP9 水平降低，4UUO 组低于 2UUO 组（P<0.05）。UUO 组 VEGF、TGF-β1、FN、Col-IV 表达高于 NC 组（P<0.05），4UUO 组高于 2UUO 组（P<0.05）。
相关性分析显示，UUO 组 MMP9 水平与 TGF-β1、VEGF、Col-IV、FN 和 RIF 指数呈负相关（均 P<0.05）。UUO 组 VEGF 水平与 TGF-β1、Col-IV、FN 和 RIF 指数呈正相关（均 P<0.05）。
随着 RIF 病变加重，MMP9 水平降低，VEGF 水平升高。它们之间是否存在相互抑制关系，有待进一步实验证实。
