| Objective：To study the expression and function of neutrophil gelatinase-associated lipocalin(NGAL), vascular cell adhesion molecule-1(VCAM-1),CD4~+CD25~+regulatory T cells(CD4~+CD25~+Treg) in the diabetic nephropathy rats andin diabetes rats treated by leflunimide.Methods：Thirty male SD rats were randomly divided into three groups:normalcontrol group(A),diabetic nephropathy models group(B) and Leflunomide (LEF)treated group(C,5mg/kg/d).Diabetes mellitus were induced in SD rats byintraperitoneal injection of streptozotocin after animals were fed by high sugar and fatdiet for4weeks.body weight,blood sugar levels,24-hour urinary protein,creatinineclearance and serum and urine NGAL, CD4~+CD25~+Treg were examined at0week,4weeks and8weeks respectively. Pathology score and kidney pathology wereobserved at8weeks, Futhermore inmmunohistochemistry were used to analyse theexpression of VCAM-1.Results：(1) serum and urine NGAL of group B progressively increased, whichwas time-dependent.Urine NGAL increased earlier than blood NGAL, the differencewas signifycant at0week (P<0.05) as compared to control greoup, same results wereobtained at4week in blood NGAL. Blood NGAL was positively correlated withurine protein (r=0.670,P<0.05) and negatively correlated with creatinine clearaneerate (r=-0.660,P<0.05) at4weeks; While urine NGAL was positively correlated(r=0.726,P<0.05) with urine protein and negatively correlated with cer endogenouscreatinine clearanee rate (r=-0.747,P<0.05) at8weeks; There was no differencebetween group C and group B (P>0.05).(2) CD4~+CD25~+Treg of group B progressively decreased in a time-dependentmanner. There were significant differences (P<0.01) at4weeks. Compared withcontrol group, LEF treatment improved the expression of CD4~+CD25~+Treg signify-cantly(P<0.05) at4weeks,however there were no significant differences (P>0.05) at8weeks. Correlate analyze showed that CD4~+CD25~+Treg was negatively correlatedwith urine protein (r=-0.633,P<0.05) and positively correlated with creatinine clearanee rate (r=0.709,P<0.05).(3) Compared with control group, the expression of VCAM-1was increased(P<0.05) in group B. The expression of VCAM-1in group C was much lower thangroup B and higher than group A (P<0.05).(4) The pathologic score in group B was higher significantly than in group A(P<0.01). It decreased afer LEF intervention. Pathologic score was positivelycorrelated with blood NGAL (r=0.811,P<0.05) and had no correlation with urineNGAL.It negatively correlated with CD4~+CD25~+Treg(r=-0.917,P<0.05).(5)CD4~+CD25~+Treg was negatively correlated(r=-0.758,P<0.05)with bloodNGAL and had no correlation with urine NGAL, meanwhile negatively correlatedwith VCAM-1(r=-0.701,P<0.05).Conclusion：(1)In early stage of diabetic nephropathy, urine NGAL stronglyexpressed,which suggested it might be a sensitive index testing in early diabeticnephropathy renal tubular damage; blood NGAL increased progressively andcorrelative with urine protein and creatinine clearance at early stage, which had greatimportance in evaluating the glomerular damage in diabetic nephropathy.(2) Type2DN kidney tissue strongly expressed VCAM-1, especially in renaltubular, which may participate in the onset and development of diabetic nephropathy.(3) The onset and development of type2DN had relevance with the disorder ofimmunity system; the expression of CD4~+CD25~+Treg decreased as the diseaseprogressed.(4) CD4~+CD25~+Treg was negatively correlated with blood NGAL, CD4~+CD25~+Treg might influence blood NGAL via effecting the inflammatory cells.(5) LEF reduced the expression of VCAM-1, increased the percentage ofCD4~+CD25~+Treg in CD4~+Treg and imprved the DN damage in diabetic rats,whichsuggested that immunosuppressant therapy may improve the prognosis of DN. |
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