| Diabetic nephropathy (DN) is the major microvascular complications of diabetes, and ultimately can lead to kidney failure,is one of the significant causes of diabetic patients’ physical disability and death. It’s a major clinical issue to explore the pathogenesis of DN and control its progression effectively and timely. The primary pathological manifestations of DN are glomerular capillary basement membrane thickening, mesangial cell proliferation and cause glomerular nodular sclerosis, pathological mechanism is very complex, including renal hemodynamics change, protein non enzymatic glycation, oxidative stress and endothelial cell injury, It is a multifactor, synergistic effect of multiple paths results. At present, there is no specific medicine for DN, the dialectical treatment for TCM and the personalized medicine regimen in DN show some advantages. According to the study, Single medicine or compound preparation of ophiopogon japonicus polysaccharide, Rhizoma Coptidis alkaloid and total saponins of Panax notoginseng can reduce blood sugar, improve insulin resistance and improve the vascular complications of diabetes.On the basis of clinical experience of advisor and research findings of DongLiang capsule at an early stage, we explore the effects of traditional Chinese medicine components (composed of ophiopogonpoly saccharide, berberine alkaloids and total saponins of panax notoginseseng) on the function of glomerulus filtration, vaso-active substance, Glycated protein and Na+-K+-ATPase of DN rats. Then we discuss mechanism of action on DN at the cellular level.Objective:To observe the effect of Chinese medicine components(中药组分) on the function of glomerulus filtration、vaso-active substance、Glycated protein and Na+-K+-ATPase of model diabetic nephropathy rats induced by STZ,wich conclude ophiopogonpoly saccharide, berberine alkaloids and total saponins of panax notoginseseng,To state the treatment mechanism of Chinese medicine components.Methods:There were 65 male rats aged 8 months(weight 180-210g),10 rats were pulled out randomly as blank control group, the others induced to diabetic model by intraperitoneal injection of Streptozotocin(STZ)(dose of 55mg/kg), After a week fasting blood-glucose passed 11.1mmol/L was considered as a successful diabetic model. 3 unsuccefful rats were eliminated, Those successful model rats were randomly divided equally into five groups, Chinese medicine components high-dose group (0.45g/kg), medium-dose group (0.15g/kg), low-dose group (0.05g/kg), metformin (0.05mg/kg) group and model group, each group rats were feed same volume medicines respectively for consecutive 4 weeks. Then we collected blood by cutting heads and taking from caudal vein, then, tested the levels of blood glucose, blood urea nitrogen (BUN)、serum creatinine (SCr)> soluble intercellular adhesion molecule (ICAM-1), P-selectin(P-S),Angiotensin Ⅰ (AngⅠ),Angiotensin Ⅱ (AngⅡ), Endothelin-1 (ET-1) in plasma and 24Upro.Results:1. The outcome of GFR show as follows:The content of the fasting blood glucose、BUN、SCr and 24Upro before administered and after 4 weeks, in diabetic model group were significant higher than the blank group, there was statistical significance (P< 0.01, P< 0.05).Compared with diabetic model group, fasting blood glucose、BUN after administered were decreased in high-dose, medium-dose group of Chinese medicine component and metformin group, SCr and 24Upro in high-dose,there was statistical significance (P<0.05).The content of the fasting blood glucose and 24Upro after administered in high-dose group were lower than medium-dose group, there was statistical significance (P< 0.05). To observe pathological changes in the kidney under light microscope, the glomerular structure in the blank group rats is clear, renal cysts wide, mesangial cells and extracellular matrix normal distribution,in the model group rats we can find glomerular swelling, hyperemia, basement membrane thickening, mesangial thickening, kidney follicle smaller was slit shaped. The pathological changes of the glomerular in the middle and high dose groups were lighter than the model group.2. The outcome of vaso-active substance show as follows:The content of ET-1, Ang Ⅰ,Ang Ⅱ,P-S,sICAM-1 in diabetic model group were significant higher than the blank group, there was statistical significance (P<0.01, P<0.05).Compare with diabetic model group, ET-1,AngⅠ, sICAM-1 decreased in high-dose, medium-dose group of Chinese medicine component and metformin group, AngⅡ, P-S decreased in high-dose and metformin group, there was statistical significance(P< 0.05),however,the content of sICAM-1 in low-dose group,medium-dose, high-dose group of Chinese medicine component, there was no difference (P>0.05) (P>0.05)3.The outcome of glycated protein in kidney and Na+-K+-ATPase in kidney show as follows:The content of glycated protein and Na+-K+-ATPase of kidney in diabetic model group were significant higher than the blank group, there was statistical significance (P< 0.01, P< 0.05).Compare with diabetic model group, glycated protein in kidney were decreased, in medium-dose, high-dose group of Chinese medicine components and metformin group, and Na+-K+-ATPase were increased,there was statistical significance (P<0.05),however,compare with diabetic model group,these index in low-dose group,medium-dose group of Chinese medicine component, there was no difference (P>0.05)Conclusion:1.Chinese medicine components can reduce the blood glucose and urinary protein excretion of diabetic nephropathy rats, regulate the charge and mechanical barrier of glomerular endothelial cell and mesangial cell, to improve the function of glomerulus filtration.2. Chinese medicine components can reduce the secretion of vasoactive substances in diabetic nephropathy rats, inhibit RAS and endothelin system activation, reduce oxidative stress, relieve the damage of glomerular endothelial and mesangial cells, It also reduce the formation of the extracellular matrix, retard the development of glomerular sclerosis, then, protect renal function.3.Chinese medicine components can reduce the formation of glycosylated protein in renal tissue of rats with diabetic renal and oxidative stress reaction by the inhibition of MAPK signal transduction pathway, reduce the fomation of mesangial cell proliferation and extracellular matrix components, It also increase the content of Na+-K+-ATPase in renal tissue, regulate water metabolism, ameliorate the function of glomerulus filtration, reduce glomerular swelling, alleviate the basement membrane thickening and protect renal function. |
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