Gliquidone decreases urinary protein by promoting tubular reabsorption in diabetic Goto-Kakizaki rats.

The efficacy of gliquidone for the treatment of diabetic nephropathy was investigated by implanting micro-osmotic pumps containing gliquidone into the abdominal cavities of Goto-Kakizaki (GK) rats with diabetic nephropathy. Blood glucose, 24 h urinary protein, and 24 h urinary albumin levels were measured weekly. After 4 weeks of gliquidone therapy, pathological changes in the glomerular basement membrane (GBM) were examined using an electron microscope. Real-time PCR, western blotting, and immunohistochemistry were employed to detect glomerular expression of receptors for advanced glycation end products (RAGE) (AGER), protein kinase C ß (PKCß), and protein kinase A (PKA) as well as tubular expression of the albumin reabsorption-associated proteins: megalin and cubilin. Human proximal tubular epithelial cells (HK-2 cells) were used to analyze the effects of gliquidone and advanced glycation end products (AGEs) on the expression of megalin and cubilin and on the absorption of albumin. Gliquidone lowered blood glucose, 24 h urinary protein, and 24 h urinary albumin levels in GK rats with diabetic nephropathy. The level of plasma C-peptide increased markedly and GBM and podocyte lesions improved dramatically after gliquidone treatment. Glomerular expression of RAGE and PKCß decreased after gliquidone treatment, while PKA expression increased. AGEs markedly suppressed the expression of megalin and cubulin and the absorption of albumin in HK-2 cells in vitro, whereas the expression of megalin and cubilin and the absorption of albumin were all increased in these cells after gliquidone treatment. In conclusion, gliquidone treatment effectively reduced urinary protein in GK rats with diabetic nephropathy by improving glomerular lesions and promoting tubular reabsorption.

[Effects of Bushen qiangdu decoction on MMP-9 and TIMP-1 produced by peripheral blood mononuclear cells in patients with ankylosing spondylitis].

OBJECTIVE: In order to investigate the roles of metalloproteinase in inflammatory bone destruction in ankylosing spondylitis (AS), and analyze the mechanism of preventing inflammatory bone destruction of Bushen Qiangdu decoction (BSQDD) in AS cases. Comparisons were made on the expressions of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) by peripheral blood mononuclear cells (PBMC) between AS patients and healthy controls. The effect of BSQDD was investigated on the expression and of MMP-9 and TIMP-1 produced by PBMC in AS patients. METHODS: From March 2005 to March 2006, 30 active AS cases of Kidney-asthenia, Du-cold and blood-stasis syndrome were selected as patients group in the China-Japan Friendship Hospital. There are 27 male patients and 3 female patients. The age range is from 16 to 45, averaging (30.8 +/- 8.8) years. Disease duration is from 0.5 to 10 years. Cases received three-month BSQDD treatment were considered as the treatment group. Twenty healthy persons were included in the control group. Serum and PBMC were separated. The PBMC were stimulated by PHA and PMA, and the supernatant was collected. The mRNA expression of MMP-9 and TIMP-1 in PBMC was analyzed by RT-PCR. The content of MMP-9 and TIMP-1 in serum and culture supernatant of PBMC were detected by ELISA. RESULTS: Compared with health control group, the serum concentration of MMP-9 and TIMP-1 in patients group before treatment increased (P<0.01, P<0.05), but the level of MMP-9 and TIMP-1 in the serum of patients after treatment decreased compared with pre-treatment cases (P<0.05). Furthermore,compared with health control group, PBMC of patients group before treatment expressed higher levels of MMP-9 and TIMP-1 both on transcript level and at protein level (P<0.01, P<0.05), and the expression levels of MMP-9 and TIMP-1 in PBMC in patients after treatment both on transcript level and at protein level was down-regulated compared with pre-treatment (P<0.01, P<0.05). CONCLUSION: PBMC of AS patients had a higher potential capacity for MMP-9 and TIMP-1. BSQDD possibly prevented inflammatory bone destruction of AS through inhibiting production of MMP-9 and TIMP-1 produced by PBMC.