ABSTRACT

Baicalin is a flavone glycoside that possesses numerous pharmacological properties. but its protective mode of action in kidney injury induced by diabetes mellitus remains incompletely understood. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin could ameliorate diabetes-induced the pathological changes of the kidney function and morphology through suppressing inflammation and oxidative stress. Furthermore, baicalin treatment could alleviate interstitial fibrosis in the diabetic kidney via inhibiting epithelial-to-mesenchymal transition (EMT), which was accompanied by a sharp upregulation of Klotho, the endogenous inhibitor of renal fibrosis. We further verified that baicalin-rescued expression of Klotho was associated with Klotho promoter hypomethylation due to aberrant methyltransferase 3a expressions. Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Baicalin in HK2 cells. These findings suggested that baicalin could alleviate renal injury-induced by diabates through partly modulating Klotho promoter methylation, which provides new insights into the treatment of diabetic nephropathy.

摘要

黄芩苷是一种黄酮苷，具有多种药理特性。但其在糖尿病引起的肾损伤中的保护作用模式仍不完全清楚。使用链脲佐菌素（STZ）诱导的糖尿病小鼠模型，我们发现黄芩苷可以通过抑制炎症和氧化应激来改善糖尿病诱导的肾功能和形态学的病理变化。此外，黄芩苷治疗可以通过抑制上皮间质转化 (EMT) 来缓解糖尿病肾脏的间质纤维化，同时伴随着肾纤维化内源性抑制剂 Klotho 的急剧上调。我们进一步证实，由于异常甲基转移酶 3a 表达，黄芩素拯救的 Klotho 表达与 Klotho 启动子低甲基化有关。通过 RNA 干扰的 Klotho 敲低在很大程度上消除了黄芩苷在 HK2 细胞中的抗肾纤维化作用。这些发现表明黄芩苷可以通过部分调节 Klotho 启动子甲基化来减轻糖尿病引起的肾损伤，这为糖尿病肾病的治疗提供了新的见解。