| Diabetic nephropathy(DN) is a major complication of diabetes mellitus and a primary cause of end-stage renal failure. So, it is of improtant clinical significance to prevent the progression toward chronic renal failure in the early stage of diabetic nephropathy.Sea cucumber, an important food and medicine resource, has lots of bioactive substances, such as sea cucumber polysaccharide, saponins, collagen proteins and cerebrosides. These substances have been proved to possess anti-oxidation, hypolipidemic, antihypertensive and immunomodulatory activities. Cordyceps militaris, one of the most valued traditional Chinese medicines, which contains polysaccharide, cordycepin, cordycepic acid and SOD, has the activities of hypoglycemic, anti-tumour, anti-aging and kidney protection. In this study, the mixture of Apostichopus japonicus and Cordyceps militaris (AC) was used to investigate the protection effect and mechanisms in diabetes nephropathy rat which was induced by a single intraperitoneal injection of Streptozotocin. Results are shown as follows:AC has remarkable suppress hyperglycemia and promote glomerular filtration rate in diabetic rats. And it could decreased the renal index (p<0.05, p<0.01), the level of BUN, Cr and UA (p<0.05,p<0.01) in serum, and decreased excretion of protein, mAlb and NAG (p<0.05, p<0.01) in urine. The AC was more effective than Apostichopus japonicus and Cordyceps militaris.The effect of AC on rugulate lipid metabolism in DN rats was detected. The results showed that AC could significantly reduce the serum TC, TG and FFA contents (p<0.05,p<0.01) and improve the ratio of hepatic SFA. It also reduced the activities of SCD and the ratio of MUFA in the liver tissue. It is suggested that AC could inhibit the synthesis of fatty acid wich attribute to the protection of renal injury in diabetic rats.Comparative investigation on the effect of AC on the anti-oxidation possibility in DN rats was also conducted. The results showed that AC could reduce the content of MDA and NO (P<0.01), increase the activities of CAT(P<0.05, P<0.01) and SOD(P<0.01) remarkably in the kidney. Therefore, AC could downregulate the level of fasting blood glucose, improve lipid metabolism and promote the activities of endogenous anti-oxidation enzymes, which attribute to the impact of preventing DN. The AC was more effective than Apostichopus japonicus and Cordyceps militaris. The AC was more effective than Apostichopus japonicus and Cordyceps militaris.The changes of renal tissue morphology in diabetic rats were observed by optical microscope and electric microscope. The results showed that AC could lessen the glomerular hypertrophy and the extracellar matrix expansion, inhibit the mesangial hyperplasia and extension; AC could also reduce glomerular basement membrane thickness, decrease the deposition of immunocomplex and lysosomes aggregation in mesangium,witch were observed under electromicroscopy. The results presented here indicated that AC could raise the pathological change of diabetic ratsThe investigation of the protection of diabetes nephropathy mechanisms of AC were conducted by RT-PCR, immunohistochemistry or western blot analysis. The results demonstrated that the TGF-β1, TβRⅡand CTGF mRNA expression were markedly increased in the kidney of diabetic rats, which were effectively suppressed by AC treatment (P<0.05, P<0.01); AC could also improve the mRNA expression level of PPARy (P<0.05, P<0.01); Western blot and immunohistochemistry analysis showed that the expression of TGF-β1 and CollagenⅣprotein was reduced significantly by AC treatment. All these rusults suggested that the beneficial effect of AC might result from its inhibiting TGF-β1, TβRⅡand CTGF expression and activating PPARy.In summary, the protective effect and its mechanism of AC on the renal in the DN rats was systemically investigated for the first time, which could further the pharmaceuticals applications of AC and supplied comprehensive and intensive theoretical basis for the clinic trial on the DN.
|
PDF Full Text Request