Effects of Cordyceps sinensis cultivated by artificial fermentation on expression of pigment epithelium-derived factor and matrix metalloproteinase-2 in diabetic rat kidney

Abstract

Objective To investigate the effects of Cordyceps sinensis cultivated by artificial fermentation on the expression of pigment epithelium-derived factor(PEDF), matrix metalloproteinase-2(MMP-2) and transforming growth factor-β1(TGF-β1) in the kidney of diabetic rats. Methods A total of 8-week-old 45 male SD rats with a weight of 180-220 g were randomly divided into three groups by randomized block design: normal group (group A, n=15), diabetic group (group B, n=15) and Cordyceps sinensis treated group (group C, n=15). The rats in group B and C were injected intraperitoneally with streptozotocin in a dose of 55 μg/g to establish the rats DM models. Three days after the animal model was established, Cordyceps sinensis was administrated intragastricly in a dose of 4 μg·g-1·d-1 at certain times in group C, and the rats were given saline in the same manner in group A and B. Twelve weeks after, the kidney mass/body mass index (KI), 24-h urinary volume, 24-h urinary albumin excretion (UAE), serum creatinine (SCr), blood ureanitrogen (BUN), triacylglycerol(TG) and total cholesterol(TC) in the three groups were measured and compared. The expression of PEDF, MMP-2 and TGF-β1 proteins and PEDF m RNA in the kidney tissue were determined by using immunohistochemistry methods and reverse transcription-polymerase chain reaction (RT-PCR) analysis in the three groups. The t test was used in the comparison between two groups and analysis of variance was used among the three groups. Results The level of KI, BUN, SCr, UAE, TC and TG in group B and C were all significantly higher than those in group A (all P<0.01), and the above-mentioned indexes in group C were all significantly lower than those in group B(all P<0.01). Immunohistochemistry showed that renal PEDF, MMP-2 protein expression in group B (1.53±0.12, 1.8±0.5) and C (2.60±0.15, 3.3±0.4) were significantly lower than those in group A(3.96±0.14, 4.3±0.6), while the TGF-β1 was higher in group B (4.60±0.15) and C(2.60±0.09) than that in group A(1.57±0.09); the expression of PEDF and MMP-2 was higher in group C than that in group B (P<0.01), while expression of TGF-β1 decreased (P<0.01). RT-PCR analysis showed that the expression of PEDF mRNA in group B and C was 0.3±0.1 and 0.8±0.2 respectively, and was significantly lower than that in group A (1.2±0.3)(all P<0.01), and it was higher in group C than that in group B(P<0.01). Conclusions PEDF, MMP-2 and TGF-β1 may play a role in the development of diabetic nephropathy. The kidney protection effects of Cordyceps sinensis cultivated by artificial fermentation in diabetic rats may be exerted through ameliorating renal function, regulating serum lipid and modulating the expression of PEDF, MMP-2 and TGF-β1. Key words: Diabetic nephropathies; Matrix metalloproteinase 2; Transforming growth factor beta1; Pigment epithelium-derived factor; Cordyceps sinensis cultivated by artificial fermentation