Abstract：
The accumulation of advanced glycation end products (AGE) plays significant role in developing tubular hypertrophy during diabetic nephropathy (DN). Reactive oxygen species and nitric oxide (NO) are directly involved in the progression of DN. We have studied the effect of standardized Gymnemasylvestre organic extract (GE) on AGE induced cellular hypertrophy using rat renal tubular epithelial cells (NRK 52E). AGE (400 μg/ml) induced cytotoxicity to NRK 52E cells as determined by MTT assay at 0-72 h. We report cellular hypertrophy mediated cytotoxicity by AGE which was the result of significant reduction in the cellular nitric oxide and cGMP levels associated with increased lipid peroxidation and antioxidant depletion (P < 0.05). Upon treatment with GE the cell viability was increased with reduced cellular hypertrophy by 1.7 folds when compared to AGE treated group. GE could significantly increase NO by 1.9 folds and cGMP by 2.8 folds and inhibited GSH depletion by 50% during AGE induced toxicity. The antioxidant enzyme activity of catalase was increased by 50% while, glutathione peroxidase and superoxide dismutase enzyme activities were significantly increased by 42% and 67% with decreased lipid peroxidation (49%) upon GE treatment. Thus, GE attenuates AGE induced hypertrophic growth by inhibiting GSH depletion and partly through increased NO/cGMP signaling.
摘要：
晚期糖基化终产物（AGE）的积累在糖尿病肾病（DN）期间发生肾小管肥大中起重要作用。活性氧和一氧化氮（NO）直接参与DN的发展。我们已经使用大鼠肾小管上皮细胞（NRK52E）研究了标准化Gymnemasylvestre有机提取物（GE）对AGE诱导的细胞肥大的影响。AGE（400μg/ml）在0-72h通过MTT测定测定对NRK52E细胞的细胞毒性。我们报道了AGE介导的细胞肥大细胞毒性，这是与脂质过氧化和抗氧化剂消耗增加相关的细胞一氧化氮和cGMP水平显着降低的结果（P<0.05）。在用GE处理后,与AGE处理组相比,细胞活力增加1.7倍,细胞肥大减少。在AGE诱导的毒性过程中，GE可使NO显着增加1.9倍，cGMP显着增加2.8倍，并抑制GSH消耗50％。过氧化氢酶的抗氧化酶活性提高了50%,谷胱甘肽过氧化物酶和超氧化物歧化酶活性在GE处理后分别显着增加了42％和67％，脂质过氧化降低（49％）。因此，GE通过抑制GSH耗竭和部分通过增加NO/cGMP信号传导来减弱AGE诱导的肥大生长。
