Project description:Diabetic rats changes gene exprssion in Shenqi Jiangtang Granule-treated rats kidney Diabetic nephropathy (DN) is a major microvascular complication of diabetes. In addition to moderating hyperglycemia, Shenqi Jiangtang Granule (SJG) had a beneficial effect on kidney function in a clinical trial. However, the mechanism involved remains unclear. This study was conducted to identify the underlying molecular mechanisms. A diabetic rat model was generated by using a high-fat diet and streptozotocin (STZ) injection. Then, rats were given SJG at dosages of 800 mg/kg/d by gavage for 8 weeks.
Project description:Diabetic rats changes gene exprssion in Qishen Yiqi Dripping Pill-treated rats kidney Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Qishen Yiqi Dripping Pill (QYDP) has been reported to be a renal protective drug. However, the mechanisms remain not certain. This study was performed to investigate the mechanisms of the extract. In this study, Sprague Dawley SD rats were fed with a high-fat diet, and injected with streptozotocin (STZ) to generate a diabetic model. Diabetic rats were administered QYDP.
Project description:Hypertension and kidney disease, two related, common, and severe disease entities have been repeatedly associated with genomic variants and metabolic alterations of lysine metabolism. Here, we developed a stable isotope labeling strategy compatible with untargeted metabolomics acquisition to investigate the physiology and molecular spectrum of lysine’s metabolic fate in vivo. Mice received 13C6 labeled lysine through the diet over two months to track more than 100 lysine metabolites across various organs and body fluids. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, as opposed to slow or incorporation into proteins and metabolization into acylcarnitines. Lysine metabolism is accelerated in the rat model of the Dahl salt-sensitive hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Here, lysine administration completely diminished the development of salt-sensitive hypertension and kidney injury. Administration of lysine leads to diuresis, even further acceleration of 13C6 lysine conjugate formation, and inhibition of albumin uptake, thereby protecting from nephron injury and metabolic stress. Lysine conjugates with malonyl-CoA to form a novel metabolite N-malonyl-lysine, to deplete malonyl-CoA from fatty acid synthesis. This process occurs at the expense of protein malonylation. In hypertensive rats with kidney damage, lysine molecules were excreted as fructoselysine, saccharopine and Nε-acetyllysine, via the urine, leading to an overall depletion of central carbon metabolites from the organism and kidney. Consistent with findings in the salt-sensitive rat, lysine challenge of patients with mild kidney damage inhibited tubular albumin uptake, increased lysine conjugate formation in the urine, and reduced TCA cycle metabolites, in contrast to kidney-healthy volunteers. In conclusion, comprehensive lysine isotope tracing mapped an accelerated lysine metabolism in hypertension, and further, lysine administration induced kidney protection in kidney disease.
Project description:In our study, we investigated the effect of methylglyoxal on metabolic, transcriptomic, metabolomic and proteomic profiles in the context of the development of kidney impairment in an experimental model of metabolic syndrome. Dicarbonyl stress was induced in experimental group by intragastrical administration of methylglyoxal (3x/ week in dose 0.5 mg/kg b.wt.for 4 weeks) in a strain of hereditary hypertriglyceridaemic rats (HHTg). Transcriptome assessment in kidney cortex was performed in 8 male adult rats of experimental group and compared to that of 6 age- and sex- matched rats of control group.
Project description:Gender has strong impact on kidney performance. Female gender tends to be renal protective. PKD/Mhm is rat model for human polycystic kidney disease (PKD) caused by a mutation in gene Anks6. PKD progresses faster in male rats compared with females. We used microarrays to detect gender-dependent gene expression in kidney of 36d old PKD/Mhm rats. Keywords: gender, genotype