| Backgroud and Objective:Diabetic nephropathy is one of the common chronic microvascular complications of diabetes mellitus, and it is also a major etiology of end stage renal disease. So it is important to explore the pathogenesis of diabetic nephropathy and look for early preventing drugs. The pathogenesis of diabetic nephropathy has not yet been fully elucidated. With the deepening of the study, it is fonud that on the basis of glycolipids metabolic disorders, diabetic nephropathy is induced by hemodynamic changes, oxidative stress, inflammation, cytokines, growth factors and other factors. Previous studies have confirmed that licorice has the pharmacological effects of inhibitingα-glucosidase, decreasing fasting blood glucose(FBG), inhibiting aldose reductase(AR) activity, antioxidation and anti-inflammatory, and it has a protective effect on renal function. But we have few studys about the pharmacological effects and mechanism of licorice to microvascular complications of diabetes such as diabetic nephropathy. Therefore, in this study, we use the method of intraperitoneal injection of streptozotocin to copy the rat model of diabetic renal injury, and investigate the protective effects of licorice extracts on the kidney of diabetic rats, further discuss the mechanism from aspects of regulation of renal AR activity, antioxidation, anti-inflammatory.Methods:1. Licorice extracts were prepared.2. The activity of licorice extracts to inhibitα-glucosidase was determinated by spectrophotometric method.3. The rat model of diabetes was established and grouped:32 male wistar rats were housed in cages and fed standard pellet diet and tap water. DM was induced by a single intraperitoneal injection of streptozotocin(STZ,65mg/kg body weight) diluted in citrate buffer, pH 4.5. Rats were randomly divided into diabetic group and therapy group, each group included 16 rats. Therapy group was gavaged by licorice extracts(1mL/100g body weight) once daily for 10 weeks. Other 16 normal male wistar rats were control group.4. Detection index:10 weeks later,24-h urine was collected for urinary creatinine, urinary albumin and urinary MCP-1. Blood was collected for FBG, GHbAlc, blood creatinine, BUN, TC, TG, MDA, SOD, SeGSHPx, AR. Ccr and KI were calculated. Kidney tissue was collected to made renal tissue homogenate to detect the content of MDA and the activity of SOD, SeGSHPx and AR. The morphological changes were observed in HE-stained sections by light microscope. The disposition of MCP-1 in kidney was detected by immunohistological staining.Results:1. The inhibition rate of licorice extracts toα-glucosidase was 52.17%.2.10 weeks later, in contrast to control group, KI, Ccr, FBG, GHbAlc, Scr, BUN, TC, TG,24-h urinary albumin and 24-h urinary MCP-1 in diabetic group and therapy group were obviously increased(P<0.05).3. In contrast to diabetic group, KI, Ccr, FBG, GHbAlc, Scr, BUN, TC, TG,24-h urinary albumin,24-h urinary MCP-1, MDA and the AR activity of blood and nephridial tissue homogenate in therapy group were obviously decreased(P<0.05). In contrast to diabetic group, the activity of SOD and SeGSHPx of blood and nephridial tissue homogenate in therapy group were obviously increased(P<0.05).4. No significant changes in kidney tissue were observed in the control group by light microscope.In the diabetic group, we could see that glomerular volume and mesangial area were significantly increased, renal tubular swelled, vacuolar degeneration of some tubular epithelial cells, distribution of interstitial focal inflammatory. Compared with diabetic group kidney lesions in therapy group significantly reduced. We observed the strong expression of MCP-1 in renal tissue of diabetic group, while there was no or rare expression of MCP-1 in control group. By immunohistochemistry, licorice extracts suppressed the expression of MCP-1 in renal tissue(P<0.05).Conclusion:1. Licorice extracts could inhibite the activity of a-glucosidase, and it could also decrease the level of FBG, TC, TG and urinary albumin.2. Licorice extracts could prevent the oxidative stress in DN.3. Licorice extracts could inhibite the AR activity in erythrocytes and renal tissue.4. Licorice extracts could prevent the expression of MCP-1 in the diabetic kidney and prevent the inflammatory process in DN. |
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