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The Variation And Value Of Neutrophil Gelatinase Associated Lipocalin In The Epithelial-Mesenchymal Transition In Children With Henoch-Sch(?)nlein

Posted on:2011-12-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y D WangFull Text:PDF
GTID:2144360302499951Subject:Academy of Pediatrics
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Background and objective:It is well known that Henoch-Schonlein purpura (HSP) is a systemic abnormal reactive vasculitis, and renal function failure induced by progressive Henoch-Schonlein purpura nephropathy (HSPN) is the primary cause of the mortality. However, the exact pathogenesis of HSPN remains unknown, and no unified and effective medicine have been found to heal HSPN. The pathological hallmarks of HSPN are mesangial cell proliferation and extracellular matrix(ECM) accumulation, which lead to increased thickness of the glomerular and tubular basement membrane(GBM) and mesangial expansion, and finally result in glomerulosclerosis and loss of the renal function. These mainly result from an imbalance between the synthesis and degradation of ECM. Recent study show that epithelial-mesenchymal transition is the key point of renal fibrosis.α-Smooth Muscle Actin, as the marker of myofibroblast, is generally used to detect the phenotype transformation from renal tubular epithelial cell to myofibroblast. Most study have indicate that neutrophil gelatinase associated lipocalin can decrease the degree of renal fibrosis by many ways and promote a certain proliferative effect on renal tubular cell. In this study, we examined the expression of a-SMA and NGAL in renal tissue of HSP children and HSPN children, also detected serum and urinary changes of NGAL in these cases, discussed their function in the development and progression of HSPN. Our results suggest novel approaches for the early diagnosis and accurate evaluation of HSPN progression.Methods:1. Subjects:Our study included 81 patients who had been diagnosed with HSP and 35 healthy children as the control. Based on the urinary albumin excretion rate (UAER) in the acute phase, the HSP children were divided into three groups. Group A (the normoalbuminuria group, N= 38), group B (the microalbuminuria group, N=26), and group C (the macroalbuminuria group, N=17). Among the above 81 patients, 22 received renal biopsy in the acute phase, including five children from group A, nine children from group B, and eight children from group C. The control kidney samples were taken from the normal portions of nephrectomy specimens of patients who underwent surgery due to trauma.2.Blood serum and urinary NGAL excretion was determined by ELISA.3. Renal pathology observation:The nephridial tissues were stained by HE and PAS seperately, then observed by a light microscope.4.α-SMA/ NGAL andⅣ-collagen expression in renal tissues: Immunoenzymic-SABC method was applied, then film reading was viewed by LEICA Qwin V3 image processing system and Image-Pro plus software was used to determine the integral optical density (IOD) ofα-SMA/NGAL andⅣ-collagen exression.5. Statistical methods:Software used:SPSS 16.0Data representation:x±SDComparison among control group and HSP groups:the least significant difference, LSD (P<0.05)Association between the urinary NGAL level and the renal NGAL expression and the renal NGAL expression with a-SMA expression:linear correlation analysisResults:1.The blood serum and urinary NGAL level in acute phase Compared with the control group, the serum NGAL level in group A and B were not found statistical difference(P>0.05), howerve, the serum NGAL level in group C was increased obviously(P<0.05). The urinary NGAL level was increased in group A (P<0.05),group B (P<0.01) and group C(P<0.01).2. The a-SMA expression in kidneyNone or little a-SMA was expressed in the renal tissues of the controls while much more a-SMA was apparently expressed in the HSP patients. The IOD ofα-SMA staining was increased with the aggravate of renal damage(P<0.05).3. TheⅣ-collagen expression in kidneyNone or littleⅣ-collagen was expressed in the renal tissues of the controls while much moreⅣ-collagen was apparently expressed in the HSP patients. The IOD ofⅣ-collagen staining was increased with the aggravate of renal damage(P<0.05).4. The NGAL expression in kidneyNone or little NGAL was expressed in the renal tissues of the controls while much more NGAL was apparently expressed in the HSP patients. The IOD of NGAL staining was increased with the aggravate of renal damage(P<0.05).5. The correlationThe linear correlation analysis revealed a tight correlation between NGAL expression andⅣ-collagen expression (r=0.823, P<0.01)The linear correlation analysis revealed a tight correlation between urinry NGAL level and renal NGAL expression (r=0.604, P=0.03).The linear correlation analysis revealed a tight correlation between NGAL expression and a-SMA expression (r=0.792, P<0.01)Conclusion:1. NGAL is related to the development and progression of HSPN, expression of NGAL will increase along with the aggravation of pathological damages in HSPN cases.2. Children with HSP has a-SMA expression, which show there exists EMT of renal tubular epithelial cells in Children with HSPN, and a-SMA has expressed in normal albuminuria group, which can indicate this change has appeared in normal albuminuria group.3. The linear correlation between NGAL expression andα-SMA expression is positive, which prompt that NGAL can accommodate the process of EMT.4. In children with HSP, NGAL levels in urine is significantly positively related to expression of NGAL, this result reveals NGAL level in urine can reflect levels of NGAL expression in renal tissue.5. The urinary NGAL is appeared in normal albuminuria group which indicate NGAL could be an early marker for predicting HSPN.
Keywords/Search Tags:neutrophil gelatinase associated lipocalin, α-smooth muscle actin, epithelial-mesenchymal transition, Henoch-Schonlein purpura, Henoch-Schonlein purpura nephritis, urinary albumin excretion rate
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