TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

Abstract

Abstract:The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese) on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCG)consisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG) 10 rats, and Uremic Clearance Granules Treatment Group (UCG) 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGF-β 1 promoter was tested by methylation-specific PCR. TGF-β 1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1) Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05), improve renal function. (2) The expression of TGF-β 1 in mRNA and protein level were down-regulated. (3) TGF-β 1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-β 1 promoter and then lead to TGF-β 1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

Ureic clearance granule, alleviates renal dysfunction and tubulointerstitial fibrosis by promoting extracellular matrix degradation in renal failure rats, compared with enalapril

“…In clinics in China, UCG is frequently used to treat the CRF patients, and that, it can significantly ameliorate renal dysfunction and tubulointerstitial fibrosis for CKD patients at stage III to stage IV (Meng et al, 2013a). The recent studies in vivo and in vitro preliminarily expounded that UCG could lessen tubulointerstitial fibrosis via depressing TGFbeta1 over-expression, inhibiting tubular epithelial myofibroblast transdifferentiation and retarding oxidative stress damage (Miao et al, 2010;Lu et al, 2013). Despite this, the deep therapeutic mechanisms involved in vivo are still unclear.…”

Hot bath for the treatment of chronic renal failure

“…37 By remethylation of TGF-beta1 promoter and then the TGF-beta1 be transcripted and translated normally, Uremic Clearance Granules (Niaoduqing Keli in Chinese) was proved to be able to reduce serum creatinine, blood urea nitrogen, and homocysteine in adenine-induced CRF rats. 38 A combination of two Chinese herbs, Astragalus membmnaceus var. mongholicus and Angelica sinensis, displayed renoprotective effects by suppression of extracellular matrix deposition, upregulation of vascular endothelial growth factor (VEGF), and reducing the loss of capillaries.…”

Niaoduqing Granules Inhibits TGF-β1-induced Epithelial-Mesenchymal Transition in Human Renal Tubular Epithelial HK-2 Cells

“…Clinical studies showed that NDQ reduced serum creatinine and blood urea nitrogen, improved renal function [6], and also alleviates CKD progression in patients with moderate-to-severe renal insu ciency e ciently [7]. In animal models, NDQ was found to reduce tubulointerstitial brosis and relieve CKD in rat, which were related with the modulation of TGF-β and erythropoietin signaling pathways [6,8,9]. However, it's still unclear that if NDQ attenuates CRF by inhibiting TGF-β1-induced EMT.…”