Effects Of Tongluo Recipe On P38 Mitogen-activated Protein Kinase-fibronectin Passway In Diabetic Rats Kidney Cortex

Diabetic nephropathy is one of diabetes important capillary vessel complications, its primary pathology is mesenteria hyperplasia,basilar membrane thickening,which lead to kidney glomeulus cirrhosis and interstitial substance fibrosis at last. P38 is one of MAPK family, it has a important function in diabetic nephropathy generation and development, which participate extracellular matrix fibrosis pathophysiology procedure. Tong luo recipe is one compound preparation by Chinese medic science meridians theory trituration, made up of ginseng, leechis, scorpion, centipede, ground beetle and red peony root et al, lots of clinic research indicate, which have protection to diabetic nephropathy. in diabetic rats kidney, TLR had action by inhibiting RAS system, anti-oxidant, ameliorating blood vessels endothelial function et al. TLR have an effect on diabetic kidney fibronectin, which have not been reported hethreto. the diabetic rats model were induced by STZ in the research, to observate TLR effect on diabetic rats kidney p38 MAPK-FN pathway relate to protein and pathology. To explore pathogenesis of the diabetic nephropathy.The research observated the control group,diabete group,TLR+diabete group rats glucose, BUN, serum creatinine, urine creatinine, left kidney weight/body weight, 24 hours urine protein/creatinine, kidney cortex PAS staining;kidney glomerulusbasilar membrane electron microscope observed, western blot detecting total-p38MAPK,phosphorylated-p38 MAPK,t-CREB,P-CREB,FN. to detect the renal function had a severity decrease, kidney glomerulus enlargement and mesenteria hyperplasia in pathology. p-p38 MAPK, P-CREB,FN protein expression increasing apparently. after TLR intervention, diabetic rats renal function ameliorate apparently, p-p38 MAPK,P-CREB,FN protein expression decreased apparently. TLR may had protection on diabete rats renal function by inhibiting the p38 MAPK -FN pathway.Objective: To study the effects of Tongluo recipe on p38 mitogen-activated protein kinase–fibronectin signal transduction pathway in the kidney of streptozotocin induced diabetic rats, so as to explore the possible mechanism by which Tongluo recipe protects the kidney. Methods: object of study : healthy, SPF Male Sprapue-Dawley(SD) rats were randomly divided into control group(n=7, model group(n=7) and tongluo recipe group(n=7. The first section: to inspect rats glucose, BUN, serum, urine creatinine, left kidney weight/body weight, 24 hours urine protein/creatinine, kidney cortex PAS staining. kidney glomerulus basilar membrane electron microscope observed. The second section: western blot detecting kidney cortex total-p38MAPK, phosphorylated -p38 MAPK, t-CREB, P-CREB, FN.Results:1. Rats general state: 1 week after STZ induced, the blood sugar>16.7mmol/L by bleeding in tail veil, diabetic model was well set up. The achievement ratio was 86.7%. blood glucose was monitored once a week, which kept over 16.7mml/L, diabetic model was kept good stabilized. Rats had polydipsia, polyuria after STZ induced 36-48h, Polyphagia, low-spirited, dryness of hair, glossiness descent appeared after STZ induced 3-4 days. After TLR treatmented, diabetic rats reaction were sensitive, the glossiness of hair had been raised little",polydipsia, polyuria,polyphagia, and weight loss"symptom to improve.2. Rats biochemical indicator:The average left kidney weight/body weight, BUN, serum creatinine, 24 hours urine protein and urine protein/creatinine were significantly increased in model group compared with the control group(p<0.05), while the average body weight was decreased.3. Renal tissues were stained by PAS. The glomerular hypertrophy and mesangial matrix expansion were shown in DM and DM+TLRgroups except the control group, and were decreased in DM+TLR group compared with the DM group.4. Kidney glomerulus basilar membrane was observed by electron microscope. The kidney glomerulus basilar membrane thickening were shown in DM and DM+TLR groups except the control group, and were decreased in DM+TLR group compared with the DM group.5. Expression of the renal cortical p-p38 MAPK, t-p38 MAPK, P-CREB, t-CREB, FN proteins in rats :The expression of p-p38MAPK, p-CREB, fibronectin was increased by 2.37-fold, 2.21-fold, 2.03-fold respectively in model group compared with those in control group (p<0.05). TLR markedly decreased the average left kidney weight/body weight , serum creatinine, 24 hours urine protein, urine protein/urine creatinine (p<0.05), TLR also had a weak effect on the level of blood sugar and BUN. The expression of p-p38MAPK, p-CREB and fibronectin were also significantly downregulated in TLR group compared with those in model group(p<0.05).Conclusion: TLR was efficient to ameliorate renal dysfunction in diabetic nephropathy rats probably by its inhibition of the activation of the p38 MAPK -fibronectin pathway .