关键词: 糖尿病肾病；粉红胶霉菌 ；链尿佐菌素；转化生长因子β1；金属蛋白酶组织抑制剂1；纤溶酶原激活物抑制剂1；模型，动物；大鼠，Wistar

Abstract:

Objective    To investigate the effect of Gliocladium roseum Bain on  expression of TGF-β1 TIMP-1 and PAI-1 in the kidneys of rats with diabetes and its relationship with pathological changes in diabetic kidneys. Methods    Twenty-four male Wistar rats were randomly and evenly divided into the normal control group(N group)， the model group(M group) and the Gliocladium roseum Bain group(G group). The diabetic rat model was established by intraperitoneal injection of streptozotocin at  a dosage of 6.5mg/100g in group M and G, while group G were intragastriced with Gliocladium roseum Bain(0.05g/100g·d)  and the other two groups were treated with normal saline at the same dosage. Blood glucose was  detected every four weeks, 24h urine protein，serum creatinine（SCr）and blood urea nitrogen(BUN) were detected at the end of the 8-week treatment,   pathological changes of nephridial tissue were observed by HE,PAS and Masson stain during the study. Expressions of TGF-β1, TIMP-1 and PAI1mRNA in nephridial tissue were detected by fluorescent RT-PCR. Results    Compared to group N, 24h urine protein, SCr and BUN in group M and  group G were significantly higher(P<0.01).Also, all the levels were higher in group M than group G (P<0.01).  Pathological changes of nephridial tissue in group N showed no obvious abnormality, while  glomerular enlargement, extracellular matrix accumulation and thickening of the glomerular basement membrane(GBM) were found in group M whose mesangial cell proliferation index was significantly higher than group N(P<0.01). The pathological changes were lighter in group G than group M. Expressions of TGFβ1, TIMP-1 and PAI-1mRNA in group  G were significantly lower than group M but higher than those of group N (P<0.01). Conclusion    Gliocladium roseum Bai has some protective and anti-glomerulosclerosis effects on early kidney injury in STZ-induced diabetic rats, partly through down-regulating  expression of  TGF-β1, TIMP-1 and PAI1mRNA, and reducing extracellular matrix and urine protein.

Key words: Diabetic nephropathy; Gliocladium roseum Bai; Streptozotocin; Transforming growth factor-betal;  Metalloproteinase-1; Plasminogen activatorinhibitor-1;  Model,animal;Rats, Wistar