Lu Qian, Yin Xiao-Xing, Wang Jian-Yun, Gao Yuan-Yuan, Pan Ying-Mei
Department of Pharmacy, Xuzhou Medical College, Xuzhou 221002, China.
Acta Pharmacol Sin. 2007 Jun;28(6):818-28. doi: 10.1111/j.1745-7254.2007.00570.x.
To observe the preventive and therapeutic effects of Ginkgo biloba extract (GbE) on early experimental diabetic nephropathy (DN) in rats.
After an early DN model was induced by streptozotocin, rats were administered GbE at 3 doses for 12 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein, kidney index, anti-oxidase, advanced glycosylation end products (AGE), collagen IV and laminin, matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), connective tissue growth factor (CTGF), and transforming growth factor-beta1 (TGF-beta1) mRNA were measured by different methods. The ultrastructural morphology and the thickness of glomerular base membrane (GBM) were observed by a transmission electron microscope.
For the GbE-treated DN rats, when compared with the vehicle-treated DN rats, the fasting blood glucose level, Cr, BUN, urine protein level, and the intensity of oxidative stress were significantly decreased. The expression of MMP-2 greatly increased, and TIMP-2 decreased. Also, AGE, either in serum or in renal, the collagen IV, laminin, CTGF levels, and TGF-beta1 mRNA were reduced. Furthermore, both relative grades of mesangium hyperplasia by microscopical observation and the thickness of GBM by electron microscope measurement decreased significantly.
GbE has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.
观察银杏叶提取物(GbE)对大鼠早期实验性糖尿病肾病(DN)的防治作用。
用链脲佐菌素诱导建立早期DN模型后,将大鼠分为3个剂量组给予GbE干预12周。采用不同方法检测空腹血糖、肌酐(Cr)、血尿素氮(BUN)、尿蛋白、肾指数、抗氧化酶、晚期糖基化终末产物(AGE)、IV型胶原、层粘连蛋白、基质金属蛋白酶-2(MMP-2)及其组织抑制剂金属蛋白酶组织抑制剂-2(TIMP-2)、结缔组织生长因子(CTGF)以及转化生长因子-β1(TGF-β1)mRNA。用透射电子显微镜观察超微结构形态及肾小球基底膜(GBM)厚度。
与给予赋形剂的DN大鼠相比,给予GbE的DN大鼠空腹血糖水平、Cr、BUN、尿蛋白水平及氧化应激强度均显著降低。MMP-2表达显著增加,TIMP-2表达降低。此外,血清及肾组织中的AGE、IV型胶原、层粘连蛋白、CTGF水平及TGF-β1 mRNA均降低。而且,显微镜观察的系膜增生相对分级及电镜测量的GBM厚度均显著降低。
GbE在DN进展过程中对多个药理靶点具有保护作用,是预防早期DN的潜在药物。