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Received Aug 18, 2017; Revised Dec 1, 2017; Accepted Dec 26, 2017
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1. Introduction
Diabetes mellitus is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period, and the incidence of diabetes in the world is increasing because of high sugar intake, high-fat diet intake, lack of physical exercise, and so on [1]. Chronic high blood sugar leads to the structural and functional lesion of multiple tissues, including the retinopathy, peripheral neuropathy, diabetic cardiomyopathy and kidney injury, and even tissue failure [2–5]. Among those complications, one of the most serious is diabetic nephropathy (DN), which is mainly characterized by accumulation of extracellular matrix (ECM) in glomeruli, as well as other secondary features: glomerular hypertrophy, proteinuria, renal fibrosis, and even renal damage [6, 7]. Now DN has become a global health problem; although the level of clinical nursing for DN patients has been greatly improved in recent years, the number of DN patients at end stage is still increasing year by year [8]. Therefore, studies should be conducted for better understanding of pathogenic mechanisms and novel therapeutic agents of DN.
Oxidative stress is involved in the pathogenic mechanisms of DN. Reactive oxygen species (ROS) are generated by sustained high glucose challenge, which are found by different teams [9, 10]; then ROS induce releasing of series fibrosis factor, promoting ECM remodeling and finally leading to renal interstitial fibrosis and damage [11, 12]. Meanwhile at DN stage, inhibiting the degradation of ECM usually leads to the accumulation of ECM in glomeruli, while matrix metalloproteinases (MMPs) system is responsible for the degradation of ECM [13, 14]. Under DN, state plasminogen activator inhibitor (PAI-1), which is the main inhibitor of activating plasminogen, is upregulated to inhibit the plasminogen activities and then to decrease the activities of plasmin and further subsequently to decrease the activates of plasmin-dependent MMPs [15]. Numerous studies have indicated that PAI-1 has a profound effect on the development of DN, and the symptom of DN would be significantly retarded after PAI-1 gene is knocked out [16]. Moreover, tissue inhibitor of...