Protective Effects And Mechanisms Of Gliocladium Roseum Bai On Early Kidney Injury In Diabetic Rats Induced By STZ

Background and Objective Diadetic nephropathy in our country has an important position in liver glomerular disease. With the increasing of diabetes incidence,the incidence of diadetic nephropathy increases a lot. Nowadays diadetic nephropathy has become the main causes of the end-stage renal failure. At present there has no specially good effective treatment to diadetic nephropathy, except strict adherence to blood glucose, rationally use ACEI and ARB, and appropriately control natrium and protein intake, certain progresses have also been made on traditional Chinese medicine and combining traditional Chinese and Western medicine. With the cytobiology and molecular biology development, a lot of researches have discovered inflammatory cells infiltrate, many cell factors and mediators of inflammatory increasing at first, and then caused glomerular extracellular matrix abnormal assemble and fibrosis. Researches show transforming growth factor-β1 (TGF-β1) is one of important growth factor in glomerular fibrosis progress. In recent years the therapy of Cordyceps sinensis on kidney disease has been focused worldwide. It could improve cell metabolize, regulate fatty metabolize, anti-oxidize, anti-fibrosis, and it has an advantage and a good prospect on controlling the clinical symptoms, improving objective indices and long-term therapeutic effects. This experiment uses Gliocladium roseum Bai which is a kind of artifical mycelia of cultivated cordyceps to treat diabetic rats induced by STZ and makes a group combined with ACEI,8 weeks later we observed the changes of every index and cell factors in kidney tissue, and discussed the protective effects of Gliocladium roseum Bai on early kidney injury in diabetic rats and its mechanisms.Methods Fourty male Wistar rats were randomly divided into normal control group(N group),model group(M group),Gliocladium roseum Bai group(G group),benazepril(B group) and Gliocladium roseum Bai plus benazepril group(GB group) each with 8.The diabetic rats model was established by intraperitoneal injection streptozotocin in a dosage of 65mg/kg in M group, G group,B group and GB group, the rats in G group and B group were intragastriced with Gliocladium roseum Bai (0.5g/kg/d) and benazepril(4mg/kg/d) respectively, the GB group was treated with Gliocladium roseum Bai plus benazepril, while the other two groups were treated with normal saline at the same dosage. The 24h urine protein,seruin creatinine (Scr) and blood urea nitrogen(BUN) were detected at the end of 8 weeks treatment.. Each four-week monitor blood glucose, in the meantime the pathological changes of nephridial tissue were observed by HE,PAS and Masson stain methods.The expressions of TGF-β1, TIMP-1 and PAI-1mRNA in nephridial tissue were detected by fluorescent quanfitation RT-PCR,the TGF-β1, LN, ColIV expression was measured by immunohistochemistry. Results (1)Compared to the N group, the 24h urine protein,SCr and BUN level in M group,G group, B group and GB group were signaficantly higher(p<0.01).The levels mentioned above were significantly higher in M group compared with other groups, while GB group was lower than G group and B group(p<0.01).There was no statistically significance in glucose level between M group,G group, B group and GB group(p>0.05).(2)Pathological changes of nephridial tissue in N group had no obvious abnormal, while the glomerular enlargement, extracellular matrix accumulation and thickening of glomerular basement membrane(GBM) were found in M group whose mesangial cell proliferation index was significantly higher than N group(p<0.01). The pathological changes were lighter in G group and B group than M group but higher than those in GB group(p<0.05).There was no significant difference between G group and B group(p<0.05).(3)The expressions of TGF-β1, TIMP-1 and PAI-1mRNA in G group and B group were significantly lower compared with M group but higher than those in N group(p<0.01). The levels of TGF-β1 and TIMP-1 mRNA in GB group was lower than G group and B group.There was no statistically significance between G group and B group(p>0.05). The level of PAI-1mRNA in GB group was lower than M group and B group (p<0.05) but no significant difference compared with G group(p>0.05).(4)The level of expressions of TGF-β1,LN and ColIV was reduced both in G group, B group and GB group(p<0.01), GB group performed significant difference with G group and B group(p<0.05).Conclusion Gliocladium roseum Bai could obviously decrease the levels of 24h urine protein,seruin creatinine (Scr) and blood urea nitrogen(BUN) in diabetic rats, reduce the expression of TGF-β1, TIMP-1,PAI-1mRNA, inhibit the accumulation of extracellular matrix, relieve pathological change of diabetic rats kidney tissue and delay glomerulosclerosis, which is similar to benazepril. The effects of combined drug treatment could play some better protective effects and anti-glomerulosclerosis effects on early kidney injury in diabetic rats than each of single drug on,...