Intervention Study Of Zhen Hua Xiao Shen An Capsule On The Relationship Between Experimental Diabetic Rat Podocyte Injury And Oxidative Stress

Purpose: Previous study considered that diabetic nephropathy(DN) is the main pathological characteristics of glomerular mesangial matrix increased, thickening of basement membrane, extracellular matrix increased, gradually as the illness, glomerular sclerosis, renal interstitial fibrosis. These pathological changes, however, can only explain 30% ~ 50% of urinary protein excretion, the pathogenesis of DN is still not completely clear. In recent years,many studies have shown that podocyte,which is the final barrier of glomerular filtration,play an important role in development of DN.ZhenHuaXiaoShenAn capsule is the clinical effective prescriptions commonly used by professor Nan Zheng,which is based on the according to the pathogenesis of DN "toxin impairing renal collaterals, evil fu film the original" theory,had quite good curative effect in clinical. This study by observing DM rat renal oxidative stress indicators of MDA, SOD,GSH-Px, and podocyte related proteins WT1, podocin, podocalyxin and α3β1 integrin expression, to explore ZhenHuaXiaoShenAn capsule’s Mechanism of diabetic nephropathy intervention from the perspective of relationship between podocyte damage and oxidative stress.Method:1 Adaptability of 70 male wistar rats fed a week, were randomly divided into normal control group(10) and module(60), made by intraperitoneal injection of module 1% STZ 50mg/kg in the preparation of experimental diabetic rats models, 72 h after STZ injection, tail vein blood sampling, measuring ≥16.7mmol/L as building success. Building successful 51 rats were randomly divided into 11 DM model group, ZhenHuaXiaoShenAn capsule high,medium and low dose group, Irbesartan tablet group 10 each. High, medium and low dose group with 1 g/kg/d respectively, 0.5 g/kg/d, 0.25 g/kg/d, to the ZhenHuaXiaoShenAn capsule suspension gavage; Positive control group to the Irbesartan suspension 20 mg/kg/d gavage,continuous gavage observation 12 weeks. To observe the general condition of rats, record 24 hours urine volume, weight; The end of the experiment records kidney weight/body weight,detection of fasting plasma glucose, 24 h urine trace albumin; Detection of cholesterol(TC),triglyceride(TG), serum creatinine(Scr), urea nitrogen(BUN).2 Observed renal ultrastructure by optical microscope and transmission electron microscopy, and observed the renal organism pathological structure changes and kidney podocytes changed for ZhenHuaXiaoShen capsule on diabetic rats kidney pathological morphological structure.3 Observed the renal tissue malondialdehyde(MDA) content, superoxide dismutase(SOD) activity and glutathione peroxidase(gsh-px) activity.4 Observed the foot cells related molecular WT1, podocin, podocalyxin protein expression using immunohistochemical method; Observed podocin, podocalyxin, α3β1integrin m RNA expression by real-time quantitative PCR.Result:1 ZhenHuaXiaoShenAn capsules can improve the experimental DM rats the general state and clinical symptoms, such as polydipsia, polyphagia, polyuria and athrepsy.2 ZhenHuaXiaoShen capsules can degrade the experimental DM rats blood glucose,triglyceride, cholesterol in a certain degree, and improve glycometabolism and lipid metabolism.3 ZhenHuaXiaoShen capsule can inhibit the experimental DM rats the early renal hypertrophy, reduce urinary albumin discharge, degrade serum creatinine and blood urea nitrogen, improve renal function.4 ZhenHuaXiaoShen capsules improve the experimental DM rats nephridial tissue pathology, reduce the thickening of the glomerular basement membrane, extracellular matrix accumulation, mesangial hyperplasy, improve podocyte morphous, thereby reducing DM glomerulosclerosis.5 ZhenHuaXiaoShen capsule can reduce experimental DM rats renal MDA content and increase SOD activity, gsh-px activity, antioxidant stress effect.6 ZhenHuaXiaoShen capsule can improve experimental DM rats kidney WT1, podocin,podocalyxin protein, increase podocin, podocalyxin, α3β1 integrin m RNA, protective effect glomerular podocytes.Conclusion:ZhenHuaXiaoShen capsules can improve the experimental DM rats the general state and clinical symptoms of polydipsia, polyphagia, polyuria and athrepsy; inhibit the early renal hypertrophy and relieve the renal pathological structure; degrade blood glucose, triglyceride,cholesterol, reduce urinary albumin discharge, degrade serum creatinine and blood urea nitrogen. ZhenHuaXiaoShen capsules can also inhibit early renal hypertrophy, reduce renal tissue pathological structure; Can improve blood sugar, blood lipid, protect renal function, its kidney protection.mechanism may be through inhibiting renal oxidative stress, increase the podocyte WT1, podocin, podocalyxin and alphaα3β1 integrin expression.My mentor professor Nan Zheng considers that the pathogenesis key of diabetic nephropathy is "toxin damaged renal meridian and hidden in pleurodiaphragmatic spaces." This experiment according to the key pathogenesis, in combination with the treatment of "toxin-relieving, meridian unblocking,tonifying kidney,spaces-tonifying" and modern medicine DN pathogenesis of oxidative stress with podocytel damage, by inhibiting renal oxidative stress and foot of glomerular filtration membrane cells related with the increase of protein expression play a role for the treatment of diabetic nephropathy.