Ji Lei, Yin Xiao-xing, Wu Zheng-mei, Wang Jian-yun, Lu Qian, Gao Yuan-yuan
Department of Clinical Pharmacology, Faculty of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
Phytother Res. 2009 Apr;23(4):477-85. doi: 10.1002/ptr.2652.
Pathological remodeling characterized by extracellular matrix (ECM) accumulation contributes to diabetic nephropathy (DN). This study evaluated the effects of Ginkgo biloba extract (GbE) on the metabolism of the ECM in rat mesangial cells cultured in hyperglycemic conditions. The cultured mesangial cells in high glucose conditions were allotted into six groups: normal control group, high glucose group, low concentration of GbE group, moderate concentration of GbE group, high concentration of GbE group, and captopril group. In the presence of high glucose, the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN) were decreased significantly, and the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) were increased significantly. These changes were reversed by GbE. GbE lowered the levels of transforming growth factor-beta(1) (TGF-beta(1)), insulin-like growth factor-1 (IGF-1) and connective tissue growth factor (CTGF) of the high glucose group. Furthermore, GbE also decreased the expressions of collagen IV and laminin of the high glucose group. In summary, the results suggest that GbE postpones the extracellular matrix accumulation by inhibiting the synthesis of ECM and promoting the degradation of ECM, and therefore, is a potential drug for the prevention and treatment of DN.
以细胞外基质（ECM）积聚为特征的病理重塑会导致糖尿病肾病（DN）。本研究评估了银杏叶提取物（GbE）对在高血糖条件下培养的大鼠系膜细胞中ECM代谢的影响。将在高糖条件下培养的系膜细胞分为六组：正常对照组、高糖组、低浓度GbE组、中浓度GbE组、高浓度GbE组和卡托普利组。在高糖存在的情况下，基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和细胞外基质金属蛋白酶诱导剂（EMMPRIN）的水平显著降低，金属蛋白酶组织抑制剂-2（TIMP-2）、金属蛋白酶组织抑制剂-1（TIMP-1）和纤溶酶原激活物抑制剂-1（PAI-1）的水平显著升高。这些变化被GbE逆转。GbE降低了高糖组中转化生长因子-β(1)（TGF-β(1)）、胰岛素样生长因子-1（IGF-1）和结缔组织生长因子（CTGF）的水平。此外，GbE还降低了高糖组中IV型胶原和层粘连蛋白的表达。总之，结果表明GbE通过抑制ECM的合成和促进ECM的降解来延缓细胞外基质的积聚，因此，是一种预防和治疗DN的潜在药物。
