Study Of The Protective Effect And Its Mechanism Of A Compound Made By Effective Components Extracted From Chinese Medicine On Diabetic Nephropathy

Objective: To investigate the influence of a compound consisting of tea polysaccharides (TPS), lycium barbarum polysaccharides(LBP) and aqueous extracts from the Eucommia Ulmoides Oliv on the indexes related to diabetic nephropathy(DN) and the cultured rat islet cell function, and explore the protective effect and its mechanism of this compound on the development of DN.Methods:Ⅰ. Experiment in vivo: The type 2 diabetic rat model was established by the injection of small-dose streptozotocin(STZ) combined with high-energy feeding. The model rats were divided into 6 groups: normal control group; Diabetic model group; The compound treated groups(low-dose, middle-dose, high-dose) and LBP treated group. All the treated groups were administered with the compound by intragatric at dosage of 162.5 mg/kg, 325 mg/kg, and 650 mg/kg, respectively; LBP group was treated with LBP at dosage of 325 mg/kg every day. After 1 month treatment, the levels of glucose, insulin, creatinine, triglycerides (TG), total cholesterol (TC), total antioxidative capacity (T-AOC), glutathione (GSH) and advanced glycosylation endproducts (AGEs) in serum, hemoglobin-Alc (HbAlc) in plasma, alodose reductase (AR) and protein kinase c (PKC) in kidney, insulin sensitivity index (ISI) were detected. The expression of transforming growth factor-β(TGF-β) in nephridial tissue was observed by immunohistochemical method.Ⅱ. Experiment in vitro: To observe the influence of the compound on the function of the cultured rat islet cells in vitro. The secretion function of the islet cell and its proliferation in different concentrations of the compound were measured.Results: Compared to the diabetic model group, the average values of glucose, creatinine, TG, TC and LP(a) in serum, HbAlc in plasma, creatinine and protein in urine of the treated-group with the compound were decreased significantly(P<0.05). Meanwhile, the average values of insulin in serum, ISI and body weight were increased significantly(P<0.05), especiall, the high-dose and middle-dose groups had the effects of relieving the hypernephrotrophy and raising the level of T-AOC in serum (P<0.05). The activity of AR in kidney tissue in the treated-group was lower than that of diabetic model rats (P<0.05). Further more, the activity in the compound treated groups approached to that of normal control group, and there was no significant difference between them(P>0.05). The average values of AGEs in serum and PCK in kidney tissue in treated-groups were lower than those of diabetic model rats significantly(P<0.05). The expression of TGF-βin kidney tissue in treated groups were decreased significantly (P<0.05), and the pathological morphology changes were improved greatly.SD rat islet cells were isolated for monolayer cell culture and treated with the compound. The activity of superoxide dismutase (SOD) and the insulin secretion of the islet cells in supernate were increased by treated with the compound compared with normal control group (P<0.05). The level of malondialdehyde (MDA) in supernate treated with high-dose compound was decreased significantly, and the high dose and middle dose of compound had the effect of reinforcing islet cells proliferation compared with normal control group(P<0.05).Conclusions: This compound consisting of LBP, TPS, and extracts aqueous from the Eucommia Ulmoides Oliv decreased the serum glucose level of the diabetic rats and promoted islet cells secretion function, and deceased the index related to renal function, such as creatinine in serum, protein in urine, and Ccr etc. The compound could protect the kidney function damaged by hyperglycosemia, and relieve the renal pathological lesion. The results showed that this compound had the protective effect on renal function in DN rats. The effect was produced by improving glucose and adipic metabolic disturbance, and relieving oxidative stress, suppressing the expression of TGF-β, PKC, and AR.