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The Variation and Value of Neutrophil Gelatinase Associated Lipocalin in the Epithelial-Mesenchymal Transition in Children with Henoch-Sch(?)nlein

Author: WangYanDong
Tutor: SunShuZhen
School: Shandong University
Course: Pediatrics
Keywords: Neutrophil gelatinase-associated carrier protein α- smooth muscle actin Tubular epithelial cell transdifferentiation Allergic purpura Purpura nephritis Urinary albumin excretion rate
CLC: R726.9
Type: Master's thesis
Year: 2010
Downloads: 106
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Abstract

Background and purpose: allergic purpura (Henoch-Schonlein purpura, HSP) is an allergic inflammation of the main pathological changes of systemic vasculitis, renal involvement or determine the prognosis of the key factors, by purpura nephritis (Henoch-Schonlein purpura nephropathy, HSPN) led to the acute and chronic renal failure is the leading cause of death of children with HSP. However, the exact pathogenesis of HSPN still unclear about its treatment is no unified and effective drugs. Known extracellular matrix (Extracellular matrix, ECM) produce too much degradation due to reduced ECM excessive deposition is the main reason of glomerular sclerosis, renal fibrosis. HSPN main pathological features of mesangial cell proliferation and accumulation of a large number of the matrix, mesangial area widened basement membrane thickening, eventually leading to the loss of the entire kidney function, with the progress of the disease is the progressive development of glomerulosclerosis. Recent studies have found that transdifferentiation of renal tubular epithelial cells (epithelial-mesenchymal transition, EMT) is a key to the renal interstitial fibrosis. α-smooth muscle actin (α-smooth muscle actin, α-SMA), as the myofibroblast marker proteins, now commonly used in the detection of renal tubular epithelial cells to muscle phenotypic transformation of fibroblasts. It has been proved that the neutrophil gelatinase-associated carrying protein (neutrophil gelatinase-associated lipocalin, NGAL) through a variety of channels affect renal fibrosis, promote tubular cell hyperplasia and repair. In this study, by observing the HSP and HSPN children with kidney tissue of α-SMA of NGAL expression and changes as well as NGAL in serum and urine, to explore its occurrence in HSPN role in the development of early diagnosis for HSPN and estimated condition to provide new ideas. Research Methods: The clinical diagnosis of HSP in children 81 cases, different according to the HSP of children with acute urinary albumin excretion rate (urinary albumin excretion rate, UAER) is divided into: normal albuminuria group (A, 38 cases): the UAER in lt; 20μg/min; microalbuminuria group (group B, 26 cases): UAER in 20-200μg/min; macroalbuminuria group (C group, 17 cases): the UAER in gt; 200μg/min or total protein gt; 50mg/kg · d. Age, sex matched normal healthy children 35 cases (20 male, 15 female, mean age 7.6 years) as a healthy control group (D). A total of 22 cases in the acute phase passing through percutaneous renal biopsy in 81 children with HSP A group of five cases, B group, 9 cases; the C 8 patients, resection in patients with renal trauma in 2 patients with no history of kidney kidney tissues. Detection of serum and urinary NGAL: enzyme-linked immunosorbent assay method (ELISA). Renal pathological morphology observed in renal tissue paraffin sections were hematoxylin - eosin (HE) and periodic acid - Sealed husband's (PAS) staining, light microscopy, the extent of damage classification of renal pathology. Kidney tissue of α-SMA of NGAL and type IV collagen expression detection of α-SMA, renal tissue was detected using immunohistochemistry SABC method of NGAL expression and type IV collagen, Applied Image-Pro plus image analysis software measurement of α-SMA, NGAL and type IV collagen cumulative optical density (IOD). 5. Statistical processing statistical analysis using SPSS 16.0 software for statistical analysis, all the experimental data the data were used as x ± s, the least significant difference (LSD) t test was used to compare the groups. Some indicators linear correlation analysis, P lt; 0.05 was considered statistically significant. Results: 1.HSP acute phase concentrations of serum and urine NGAL change: Compared with the normal control group, the A and B group were serum NGAL concentration change was not statistically significant, the C group was significantly higher (P lt; 0.05 ); compared with the normal control group, A, B, C group of children with urinary NGAL levels were significantly higher (A group P lt; 0.05 in group B P lt; 0.01 in group C P lt; 0.01), and urine with white The increase in the rate of protein excretion showed an increasing trend (P lt; 0.05): the expression of α-SMA 2.HSP renal tissues of children: in normal kidney tissue, only a little or no expression of α-SMA, HSP children with kidney compared with a marked increase in the expression of α-SMA, and showed an increasing trend in the A, B, C group (P lt; 0.05). Expression of type IV collagen 3.HSP renal tissues of children: just a small amount or type Ⅳ collagen expression in normal kidney tissue type IV collagen expression of HSP children with kidney tissue compared has increased significantly, and in the A , B, C group showed an increasing trend (P lt; 0.05). Of NGAL expression 4.HSP renal tissues of children: in normal kidney tissue, only little or no NGAL expression, compared with a significant increase in the expression of the HSP children with renal tissue of NGAL, and in the A, B, C group was increasing trend (P lt; 0.05). 5. Correlation analysis results show renal tissue NGAL and type Ⅳ collagen expression was positively correlated, (r = 0.823, P lt; 0.01); HSP renal tissues of children of NGAL expression and urinary NGAL level was positive related (r = 0.604, P = 0.03 ); HSP in children with renal tissue of NGAL expression of α-SMA expression was positively correlated (r = 0.792, P lt; 0.01). Conclusions: With increased urinary albumin and renal pathological damage increased NGAL levels and kidney tissue of HSP in children with urinary NGAL also showed an increasing trend, suggesting of the NGAL with of HSPN the occurrence and development related. Renal tissues of children 2.HSP presence of abnormal expression of α-SMA, renal tubular epithelial cell transdifferentiation show that the existence of in HSPN the occurrence and development, and α-SMA in normal albuminuria group had expressed, that such a transformation in normal the albuminuria group had occurred. 3. Kidney tissue NGAL and α-SMA was positively correlated prompted NGAL might EMT from regulation. Children of urine NGAL 4.HSP level of kidney tissue NGAL expression was positively correlated to the the, prompt urine NGAL level can reflect the level of expression of NGAL in the kidney tissue. 5.HSP children with urinary NGAL levels in normal albuminuria group has increased, suggesting that as early as in the early diagnosis of urinary albumin HSPN sensitive indicators.

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