Study The Expression And The Interference Of AGEs-RAGE System On Diabetic Nephropathy

Part I Clinical datas of diabetic nephropathy patients and longterm hemodialysis diabetic patientsObjective To elucidate the accumulation of LMW-AGEs(low molecular weight -advanced glycation end products) in patients with different kidney damageand observe the effects of Jinqi tablet combined with pancreatic kininogenase entric-coated tablets(PKE) on phase III diabetic nephropathy. Methods Determinated the fluorescent intensity of AGEs in serum of control subjects(N),diabetic patients without nephropathy(DM) and patients with different renal lesions (microalbuminuria, macroalbuminuria, nitremia and uremia). On the other hand, 80 phase III diabetic nephropathy patients were randomly divided into the A group(42) and the B group(38).A group was treated by Jinqi tablet combined with PKE, B group was treated by PKE only. All patients were observed the changes of HbA₁C, UMA, AGEs after 12 weeks interference. Result l.Fluorescent intensity of LMW-AGEs in serum: :Group N was lower than group DM;Group DN1 was lower than group DN2 and group DN3 was lower than group U but there was no difference between group DM and group DN1.So was between DN2 and DN3.2. After interference for 12 weeks, Two groups were significantly decreased in HbA₁C and UMA. A group was reduced in Homa-IR and AGEs too. The level of Homa-IR, UMA and AGEs in A group were significantly lower than those in B group but insignificant difference was found in HbAiC between two groups. Conclusion It would be valuable in diagnosis of early-stage nephropahty, determination of renal damage and assessment of end-stage renal failure to measure the fluorescent intensity of LMW-AGEs and it has important significance in prevention and therapy of diabetic complications too. Jinqi tablet combined with PKE can remedy diabetic nephropathy in early phases.Part II Study the expression and the interference ofAGEs-RAGE system on diabetic ratsObjective To observe the expression of AGEs^ RAGE> NF- k B> VEGF> TGF — 3 1 and CTGF in the kidney of diabetic rats and research their inhibitor. Methord Determinated the level of AGEs, RAGE, NF- k B> VEGF> TGF— ^ 1 and CTGF in the kidney of diabetes group(group DM), diabetes with jinqi tablet(group DD) and control group(group N) at 4thweek, 12thweek and 20thweek. Results l.FPG: group DM (23.47±4.12mmol/l) and group DD (23.31±4.13 mmol/1) are higher than group N(5.42±0.51mmol/l,P<0.001). It is no difference in FPG between group DD and group DM.2..AGEs:4thweek: It is no difference in AGEs among group DD , group DM and group N;12th week and 20th week:The level of AGEs in group DM is higher than group N (p<0.05);3.RAGE: 4thw: The level of RAGE(mRNA and protein) in group DM is higher than group N (p<0.05) but It is no difference in RAGE between group DD and group DM,so was between group DD and group N. 12thw and 20thw:Group DM has more RAGE than group DD(p<0.05) and group N(p<0.01). The level of RAGE between group DD and group N is no difference. 4. NF- K B: It is no difference in NF- K B among group DD , group DM and group N at 4 th week and 12 th week. The level of NF-KB in group DM is higher than group N (p<0.01) and group DD(P<0.05). The level of NF- K B between group DD and group N is no difference(p>0.05). 5.VEGF: The level of VEGF in group DM, group DD and group N are no difference at 4 th week.(p>0.05) Both mRNA to protein of VEGF in group DM are higher than group N (p<0.05) but It is no difference in VEGF between group DD and group DM, so was between group DDand group N at 12 th week. The level of VEGF(mRNA and protein) in group DM is higher than group N (p<0.001) and group DD (p<0.001) at 20th week. It is no difference in VEGF between group DD and group N. 6. TGF-Pi: At 4th week ,the level of TGF- P 1-mRNA in group DD is higher than group N (p<0.05) but It is no difference in TGF- P 1-mRNA between group DD and group DM. It is no difference between group DM and group N yet. The protein levels of VEGF are no difference among three groups. Both mRNA (p<0.001) to protein (p<0.01) of TGF- P 1 in group DM are higher than group N and group DD, but It is no difference in TGF- P 1 between group DD and group N at 12 th week. At 20 th week,the level of RAGE(mRNA and protein) in group DM is higher than group N (p<0.001) and group DD (p<0.001) .The mRNA level of group DD is higher than group N (p<0.001) but the protein level is no difference. 7.CTGF: The level of CTGF(mRNA and protein) in group DM, group DD and group N are no difference at 4 th week.(p>0.05). Atl2th week ,the level of CTGF-mRNA in group DM is higher than group N(p<0.001) and group DD(p<0.05).But the level of protein is no difference among three groups. Both mRNA to protein of VEGF are no difference between group DD and group N. Both mRNA(p<0.001) to protein(p<0.01) of VEGF in group DM is higher than group N and group DD at 20 th week. But it is no difference in both mRNA to protein of CTGF between group DD and group N, Conclusion :1.We can make diabetic rats by streptozotocin vein injection.2.The level of AGEs^ RAGE> NF- k B^ VEGFs TGF— P 1 and CTGF is intensive correlated with diabetic nephropathy. The pathway of RAGE—oxidative stress—P21?/ MAPK —NF- K B may bridge a lot of factors which cause tissue injured and RAGE may be a critical role in this pathway. 3.It is to release renal hurt of diabetes for taking jinqitablet for long time AThe renal protection of jinqi tablet is independence on the control of blood sugar and it may be related with the inhibition of AGEs % RAGE -. B^ VEGF. TGF- P 1 and CTGF.