| Recent studies indicate that the number of patients with chronic kidney disease (CKD) in China is about 119 million, which causes a great burden to the society and economy. Glomerular disease continues to be the leading cause of CKD in China. Recently, the damage and repairof podocytes has become a hot topicin kidney disease research. MiRNAs are a set of endogenoussmall molecules,20-22 nucleotides in length, that are widely present in plants, animals, viruses, and humans. They are highly conserved and tend to exhibit a region-specific expression from large gene clusters. Previous studies have shown that microRNAs can modify gene expression, and microRNA deregulation is correlated with major kidney diseases. The Traditional Chinese Medicine (TCM) provides us with valuable theories and rich clinical experience, especially in the field of CKD. TCM gives us curative therapeutic effect, and it has the incomparable advantage for modern medicine. This study is to focus on the mechanism of podocyte protection from Traditional Chinese Compound Prescription and Chinese Herbal Monomer.Study I:The Study of YiShenQingLiHuoXue Decoction on the expressions of microRNA and podocyte Injury in Rats with Adriamycin-induced NephropathyObjectives.To investigate the action of YSQLHXF in rats with adriamycin-induced nephropathy and evaluate the possible mechanisms underlying its protective effect against podocyte injury.Methods. In total,30 healthy male Sprague-Dawley rats were randomized into three groups (normal group, model group, and YSQLHXF group).On days 7,28,42, and 56,24-h urine samples were collected. All rats were sacrificed on day 56, and their blood sample and renal tissues were collected for determination of biochemical and molecular biological parameters. Expression of miRNAs in the renal cortex was analyzed by a biochip assay. Results. YSQLHXF decreased proteinuria, improved renal function, alleviated renal pathological lesions, and increased the nephrin protein level. Furthermore, levels of miRNA-494-5p、miRNA-1249、 miR-3596c were elevated in rats with adriamycin-induced nephropathy, and levels of miRNA-582-5p were downregraded in rats with adriamycin-induced nephropathy, while YSQLHXF treatment reversed these changes in the expression of those two miRNAs.Conclusions. YSQLHXF may attenuate podocyte injury in rats with adriamycin-induced nephropathy by regulating the expression of miRNA-494-5p、 miRNA-1249、miR-3596c、miRNA-582-5p.Study II:The Study of Triptolideon the expressions of microRNA and podocyte injury in Rats with Adriamycin-induced NephropathyObjectives.To investigate the action of triptolideon rats with adriamycin-induced nephropathy and evaluate the possible mechanisms underlying its protective effect against podocyte injury.Methods.In total,30 healthy male Sprague-Dawley rats were randomized into three groups (normal group, model group, and triptolide group).On days 7,28,42, and 56,24-h urine samples were collected. All rats were sacrificed on day 56, and their blood and renal tissues were collected for determination of biochemical and molecular biological parameters. Expression of miRNAs in the renal cortex was analyzed by a biochip assay and RT-PCR was used to confirm the differences in miRNA levels. Results.Triptolide decreased proteinuria, improved renal function without apparent adverse effects on the liver, and alleviated renal pathological lesions. Triptolide also elevated the nephrin protein level. Furthermore, levels of miR-344-3p and miR-30b-3p were elevated in rats with adriamycin-induced nephropathy, while triptolide treatment reversed the increase in the expression of these two miRNAs.Conclusions.Triptolide may attenuate podocyte injury in rats with adriamycin-induced nephropathy by regulating expression of miRNA-344-3p and miRNA-30b-3p.Study III:The comparison the therapeutic effectbetween YSQLHXF and Triptolide in rats with adriamycin-induced nephropathyObjectives.To investigate the actions of YSQLHXF and triptolide in rats with adriamycin-induced nephropathy and compare the effects.Methods.In total,40 healthy male Sprague-Dawley rats were randomized into four groups (normal group, model group, YSQLHXF group, and triptolide group).On days 7,28,42, and 56,24-h urine samples were collected. All rats were sacrificed on day 56, and their blood and renal tissues were collected for determination of biochemical and molecular biological parameters. The expression of nephrin protein was detected by immunohistochemistry and west-blot method. The expression of nephrin nucleic acid in kidney tissue was detected by RT-PCR. Results. YSQLHXF and triptolidereduced proteinuria, improved renal function without apparent adverse effects on the liver, and alleviated renal pathological lesions.Compared with triptolide, YSQLHXF improved the level of serum albumin in the rats with adriamycin-induced nephropathy. Conclusions. YSQLHXF and triptolide may attenuate podocyte injury in rats with adriamycin-induced nephropathy by regulating expression of nephrin. |
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