| Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus. Proteinuria is not only the manifestation of DN but an important factor in DN progression. It is important to seek a more effective method to reduce proteinuria in the management of DN. The present paper carried out a meta-analysis for the randomized controlled trials evaluating Chinese herbal combination prescriptions supplementing Qi and activating blood circulation for proteinuria reduction in patients with DN. The present paper also studied the effect of a Chinese herbal combination prescription, namely, Qingre Tonglu, on proteinuria in DN rats induced by Streptozotocin (STZ) and its potential mechanism.Objectives:study the effect of Qingre Tongluo on proteinuria in DN rats induced by STZ and its potential mechanism..Methods:Type 1 diabetic nephropathy rat model was induced by STZ intraperitoneal injection. The rats were randomly assigned into four groups:normal control group, modeling group, Qingre Tongluo group and irbesartan group. Twelve weeks after successful modeling, the changes in the weight, fasting blood glucose (FBG),24 h urine volume and urinary protein and renal function were studied; the morphological changes in the glomeruli, tubules and interstitium were studied by light microscope and electron microscope; the changes in the mRNA expression of podocyte proteins, i.e., Nephrin and Podocin, were studied by in situ hybridization and the changes in positive expression area and intensity were semi-quantified. Results:at the end of experiment,â‘ compared with normal control rats, the weight of DN rats reduced while FBG and 24 h urine volume increased. The differences between normal rats and DN rats about these measures were statistically significant. Compared with normal rats, the 24h urinary protein was statistically increased in DN rats. The rats received irbesartan showed a reduction in 24h urinary protein and the difference between irbesartan and modeling group was statistically significant. The 24h urinary protein reduced in Qingre Tongluo group and the difference between Qingre Tongluo group and irbesartan group was statistically significant.â‘¡No obvious pathological changes were found in HE stained sections. This result was in line with the first grade pathological change in the four-grade DN classification system.â‘¢The results of electron microscope showed that the glomerular basement membrane (GBM) thickened in DN rats. The difference between normal rats and DN rats was statistically significant. When received irbesartan and Qingre Tongluo, the thickening degree of GBM obviously alleviated and, compared with modeling group, the difference was statistically significant.â‘£The results of in situ hybridization demonstrated that the expression of Nephrin mRNA reduced in DN rats. Compared with normal rats the difference was statistically significant. Irbesartan improved the reduction in Nephrin mRNA in DN rats and the difference between modeling group and irbesartan group was statistically significant. Compared with irbesartan, the difference about Qingre Tongluo improve the reduction in Nephrin mRNA was statistically significant. Compared with normal rats, the expression of Podocin mRNA in DN rats reduced and the difference was statistically significant. Both irbesartan and Qingre Tongluo could ameliorate the reduction in Podocin mRNA in DN rats and compared with modeling group the difference was statistically significant.Conclusions:â‘ The method could be used in early stage DN modeling that a single intraperitoneal injection of STZ after 14 weeks. The pathological change of this model is in line with the first level in the four-grade DN classification system.â‘¡Qingre Tongluo could reduce the proteinuria in early stage DN.â‘¢One of the mechanisms by which Qingre Tongluo reduces proteinuria is its antagonism against the downregulation of Nephrin and Podocin.â‘£One of the mechanisms by which Qingre Tongluo reduces proteinuria is its antagonism against the thickening of glomerular basement membrane.
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