| Diabetic nephropathy (DN), which is one of the Dabetes (DM) chronic microvascular complications, is a serious long term complications and the leading cause of death. In the United States, DN accounted for 25% to 40% of the total number of patients with diabetes, while DN has become the first cause of end-stage renal disease(ESRD). Therefore, how to prevent DN disease progression, its medical research has become a hotspot and difficulty. The role of TCM for the DN is a multi-target, multi-channel, multi-link, multi-level, which is the advantages of medical prevention and treatment, so the mechanism research of TCM for DN is very important. In this thesis, based on the preliminary PNS (Panax notoginseng saponins, PNS) monomer laboratory studies on adriamycin renal and DN fibrosis, we test STZ DN rats TGF-β1 (Transforming growth factorβ1, TGF-β1), p-p38MAPK (Phosphorylation of p38 Mitogen-activated protein kinase, p-p38MAPK), Caspase-3 protein and gene expression, and to explore the mechanism of PNS treatment of DN.Objective:In order to investiga te the mechanism of RNS in relief DN from levels of organ, tissue, cell, protein and gene, we established DN rat model and high glucose cell model then observed the efficiency of PNS in influence TGF-β1, p38MAPK, Caspase-3 gene and protein's expression, and provide a theoretical basis for the treatment of DN.Methods:Intraperitoneal injection of STZ(55 mg/kg) was used to build diabetic rats that were divided into normal group, model group, IRB group, PNS group. Rat body weight,24-hour urine protein test, test at 12 weeks, measured kidney weight body weight ratio, serum levels of serum triglycerides (Triglyceride, TG), blood urea nitrogen (Blood urea nitrogen, BUN), creatinine (Serum creatinine, Scr), NO (Nitric oxide, NO), MDA (Malondialdehyde, MDA) and superoxide dismutase (Superoxide dismutase, SOD) concentration; kidney HE, mallory, masson, methenamine silver staining; immunohistochemistry and RT-PCR detection of renal TGF-β1, p-p38MAPK, Caspase-3 protein and mRNA. Observed in vitro experiments with PNS on glucose podocyte TGF-β1, p38MAPK, Caspase-3 mRNA expression. Experimental data were analyzed statistically with SPSS 16.0.Results:1 Compared with model group, the body weight increased in all the other groups, and there is significant statistics difference in 8,10,12 weeks(P<0.05); The kidney weight/body weight ratio of PNS group were significantly decreased(P<0.01); the Urine protein of PNS group and IRB group were significantly decreased (P<0.01) at the end of the 4 and 8 week, and also decreased (P<0.05) at the end of the 12 week (P<0.01). And PNS also decrease the biochemical parameters such as BUN, Scr and TG. Compared with model group, the BUN of all the other groups were significa ntly decreased (P<0.01).The IRB and PNS group glomerular sclerosis index and interstitial damage examination scores significantly reduced (P < 0.01), PNS can reduce DN renal tissue pathology damage.2 Compared with the normal group, the model group MDA was increased, but there is no statistically significant differences; Compared with the model group, and IRB and PNS groups SOD,NO were significantly reduced (P< 0.01),.3 The model group renal tissue TGF-β1 protein, TGF-β1 mRNA, p-p38MAPK, Caspase-3 protein levels were significantly higher than the normal group(P< 0.01). PNS group TGF-β1 protein, TGF-β1 mRNA, p-p38MAPK, Caspase-3 protein levels compared with model group was significantly lower (P<0.01).4 Compared with the normal group, high sugar TGF-β1 podocyte group TGF-β1 and Caspase-3 gene expressions were increased significantly (P< 0.05), but there is no significantly difference of p38MAPK gene expression in all the groups (P> 0.05); Compared with high sugar groups, PNS group podocyte TGF-β1, Caspase-3 gene level were significantly reduced (P< 0.05), but the p38MAPK gene expression had no difference (P> 0.05).Conclusion:1 PNS can reduce oxidative stress in DN rats, cure the renal pathological changes, and protect renal function;2 Regulating renal TGF-β1, p38MAPK, Caspase-3 protein and gene expression may be the one of the mechanisms of PNS cure of DN.3 Control of high glucose podocyte TGF-β1, p38MAPK, Caspase-3 gene expression, may be the mechanism of PNS to prevent cell apoptosis of DN.4 Controling TGF-β1/p38MAPK signaling pathways may be the material foundation of the PNS resistance of renal fibrosis, which enrich Chinese medicine YI BING TONG ZHI theory connotation, provides new evidence of the clinical treatment for DN. |
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