Experimental Study On Protection Of Spleen-Strenthening Kidney-Supplementing And Blood-Flow-Promoting Traditional Chinese Recipe To Diabetic Nephropathy And Its Mechanism

Object:To invastigate the protective effect of spleen-strenthening, kidney -supplementing and blood-flow-promoting (SKBP) recipe to the kidney of diabetic rats and its pharmacodynamic mechanism.Method:Using rats as subjects to set up the animal models of spleen deficiency through giving the rats irregular and high fat diet for two weeks, and set up the diabetic models by injection of streptozotocin (STZ) . Then the Rats were treated with SKBP recipe for eight weeks, taking TRITACE as the comaparative drug. The invatigated items are: ( 1) blood glucose; (2) body weight (BW) , renal weight (Rw) and RW/BW; (3)a-24-hour urinary albumin (UAlb); (4) serum creatinine (Cr); blood urea nitrogen (BUN); (5) serum triglyceride (TG); tatol cholesterol (TO; (6) superoxide dismutase (SOD) and malondialdehyde (MDA) in renal cortex; (7) serum thromboxane B2 (TXB2) and 6-keto-prostaglandin Fl a (6-Keto-PGFl a ); (8) transforming-growth factor P ,mRNA in renal cortex; (9) pathological change of renal tissues.Results:The spleen-deficiency rat modals, with the presentation of huddled body and diarrhea, were set up by giving them irregular and hih fat diet; and diabetic rat models with feature of high blood glucose were set up 72 hours after intra-abdomiral injection of STZ, 53mg/kg, once. The modals were good. The diabetic modal rats, with the course going on, presented the feature of spleen deficiency such as huddled body, lassitude, listlessness, thinned skin hair and diarrhea, which was similar to what disease-syndrome combined rats did.The expression of TGF- P imRNA in renal cortex of modal rats in diabetic and disease-syndrome combined groups were enhanced, and the content of MDA increased; on the other hand, the expression of TGF-P imRNA and the content of MDAwere also significantly correlated with increase of UAlb, but the latter might be the result of the former. SKBP recipe could reduce UAlb of modal rats in disease-syndrome combined group; decrease contents of serum TG; increase activities of SOD and lower contents of MDA in renal cortex; decrease contents of serum TXB2 and increase contents of serum 6-Keto-PGFl a ; inhibit hyper-exprossion of TGF- 1mRNA, etc.. Of these, the actions of SKBP in lowering hyperlipoidemia, reducing hyperoxide injury, and anti-platelet aggregation were better than that of TRITACE; and the action of SKBPin inhibiting hyper-expression of TGF-β1mRNA was similar to that of TRITACE. The results in both optical and electron microscopy of kidney tissues in pathological morphology showed that SKBP could reduce renal hypertrophy, mean glomerular section areas, and mesangial hyperplasia and podocytic process fusion, which was similar to what TRITACE did. Conclusion:1. Diabetic modal rats set up by STZ had characteristic presentation of spleen deficioncy. The deficiency of spleen Qi is the pathological basis of diabetes mellitus.2. The pharmacodynamic mechanism for SKBP recipe in protection of the kidney of diabetic rats were:(1) Reducing discharge of a-24-hour UAlb.(2) Inhibiting hyper-expression of TGF-β1mRNA in renal cordex.(3) Decreasing content of serum TG.(4) Increasing activity of SOD, and reducing content of MDA.(5) Decreasing content of TXB2 and increasing content of 6-Keto-PGF1a .(6) Reducing renal hypertrophy, decreasing mean section areas of the glomeruli, and reducing mesangial hyperplasia and podocytic process fusion.3. Increase of MDA in renal cortex may lead to increased excretion of UAlb.4. Hyper-expression of TGF-β1mRNA may result in high excretion rate of UAlb.