| 1 Study backgrounds and objectionsDiabetic nephropathy (Diabetic nephropathy, DN) is the most common complication of diabetes, and also is one of important reasons which leads to the chronic renal insufficiency. Diabetic nephropathy the exact pathogenesis has not yet been clarified , Much experimental and clinical data show that immune injury may be the key aspect in the pathogenesis of DN . In recent years , CD4 + CD25 + Treg cells to prevent pathological immune response to injury aroused widespread interest, CD4 + CD25 + Treg cells maintained the body's own stability through a proactive approach , it chould inhibit the immune response, played some role in the immune pathology,immune tolerance and maintenance of immune balance. Type 1 diabetes is an autoimmune disease., by T cell-mediated, resulting in selective destruction of pancreatic islet B cells. Studies of patients with T1D had found that CD4 + CD25 + Treg cells generally appear to reduce the quantity or diminished ability to regulate in the patient's body. Similarly, Observation of non-obese diabetic (NOD) mice also found that CD4 + CD25 + Treg cells appear to reduce the quantity in sick mice. Then CD4 + CD25 + Treg cells in the expression level of DN patients, in DN pathogenesis of whether the work, at home and abroad there is no relevant reports. By detecting the number of CD4 + CD25 + CD127-Treg cells and the expression level of Foxp3mRNA in peripheral blood of patients with T2DN, the aim of the present study was to investigate whether Treg cells play role in the pathogenesis of T2DN.In recent years, studies have shown that connective tissue growth factor (CTGF) occupied an important position in the occurrence of DN as a new Desmoplastic growth factor. CTGF led to extracellular matrix deposition through its own or in conjunction with other cytokines to promote renal cell mitosis, regulate the cell cycle restriction point, increase extracellular matrix synthesis, reduce extracellular matrix degradation , Finally result renal hypertrophy, glomerular sclerosis and renal tubule fibrosis, mediate the occurrence and development of DN. A large number of animals and clinical trials confirm that, angiotensin II receptor blockers (ARBs) play the role of reducing proteinuria and delaying the deterioration of renal function.one of the mechanisms of renal protection is inhibiting the expression of renal cell CTGF by antagonistic AⅡ, to reduce the deposition of ECM in renal tissue, thereby delaying or blocking of diabetic nephropathy kidney hypertrophy and fibrosis and improving renal function. Fluvastatin, hydroxymethyl-Coenzyme A reductase inhibitor, has been widely applied at the Treatment of kidney disease as a classic and effective lipid-lowering drugs. In recent years, animal experiments and clinical confirm that statins may be through non-lipid-lowering dependent pathway on renal protective effect, but its mechanism is not yet completely clear. Song found that fluvastatin may inhibit CTGF- mediated ECM accumulation to prevent the occurrence of fibrosis in diabetic nephropathy. through studying the 5 / 6 nephrectomized rats. In this study, we explore the role of CTGF in the pathogenesis of diabetic nephropathy by detecting the expression level of CTGF in blood in patients with diabetic nephropathy , we separately give valsartan and fluvastatin to DN patients,after detecte 24 hours urinary albumin excretion rate and the levels of CTGF in patients before and after drug intervention , finally explore the effect of valsartan and fluvastatin on diabetic nephropathy and the mechanism..2 Experimental Subjects and methodsAccording to the diagnostic criteria of diabetic nephropathy ,we selected Type 2 diabetic nephropathy (T2DN) patients in our hospital in 2008, and randomly selected age-matched healthy volunteers as the control group (NC),.All the objects had no acute or chronic infections and other autoimmune diseases. we divided patients into diabetic nephropathy + valsartan treatment group (DA group), diabetic nephropathy + fluvastatin treatment group (DF group) according to medication , after observated 3 months. Collecting blood ,we Detected the number of CD4 + CD25 + CD127-Treg cells by flow cytometry and the expression level of Foxp3mRNA by RT-PCR technology in peripheral blood of all the objects, the concentrations of CTGF in blood by ELISA. Collecting 24-hour urine, we detected 24-hour urinary albumin excretion rate. Finally the treatment group compared before and after Tregeatment..3 Statistical analysisMeasurement data was performed by using mean±standard deviation (±s), using SPSS12.0 software analysis, groups compared with the T test, P <0.05,or P <0.01 for the difference between statistical significance.4 Results(1)the number of CD4 + CD25 + CD127-Treg cells and the expression level of Foxp3mRNA of NC and T2DN group in peripheral blood mononuclear cells(PBMCs) have no significant difference (P> 0.05). Since no difference between the two groups, we did not test their expression after drug treatment..(2)the concentration of CTGF in blood in the T2DN was more than NC group (P <0.01); Compared with before treatment, the expression of CTGF in the DA group, DF group was significantly reduced (P <0.01), but there was no significant difference between the two groups in the level of Decline(P>0.05). 24-hour urinary albumin excretion rate in the DA group, DF group was significantly reduced (P <0.01), but there was no significant difference between the two groups in the level of Decline(P>0.05).5 Conclusions(1) CD4 + CD25 + CD127- Treg cells have no significant change in Type 2 diabetic nephropathy, it possibly does not work in the pathogenesis of Type 2 diabetic nephropathy .(2) The expression of CTGF in blood in the DN obviously increased, CTGF may play an important role.in the pathogenesis of diabetic nephropathy.(3) Fluvastatin and valsartan can improve diabetic kidney disease by reducing the expression of CTGF, and have the role of slowing the progression in diabetic nephropathy.(4) Fluvastatin and valsartan.have the same role of improving diabetic nephropathy . |
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