The Study On The Influence Mechanism Of SREBP-2-LDLr Pathway In The Lipid Deposition In Kidney Of IgA Nephropathy In Children

PART ONE: THE SPECTRUM CHANGE OF INPATIENT URINARY SYSTEM DISEASE IN THE LAST 15 YEARS IN CHILDREN'S HOSPITAL OF CHONGQING MEDICAL UNIVERSITYObjective To understand the spectrum change state of urinary system disease in the last 15 years in children's hospital of chongqing medical university.Methods The data of inpatient children with urinary system disease from January 1, 1993 to December 31, 2007 were analysed retrospectively.Results The number of inpatient increased year by year. The ratio of male to female is 2.49 : 1, and 3522 cases were the children of age 7 to 14, accounting for 50.14%; primary glomerular diseases (PGD) with the largest proportion, but the proportion was in downward trend; the proportion of secondary, hereditary glomerular disease was in upward trend; constituent ratio of Henoch-Schonlein purpura nephritis, IgA nephropathy, interstitial nephritis was significantly increased; isolated hematuria was in downward trend; an upward trend was shown in the hospitalized number of congenital malformations, hydronephrosis and lithangiuria.Conclusion The spectrum of urinary system disease had changed among inpatient children in Children's Hospital of Chongqing Medical University during 15 years.PART TWO: THE PRELIMINARY STUDY OF THE ROLE OF SREBP-2-LDLR PATHWAY IN LIPID DEPOSITION IN HMCs WERE CO-CUITURED WITH SERUM OF IgANObjective To understand the situation of mesangial cell proliferation and lipid deposition in the serum enviroment of different IgAN patients and the relationship between the lipid deposition and the expression of LDLr, SREBP-2.Methods Serum of IgAN patients and HMC were co-cultured; mesangial cell proliferation was detected by MTT; lipid deposition in mesangial cell was detected by Oil Red O staining; the mRNA expression of LDLr, SREBP-2 in mesangial cell was detected by RT-PCR; the protein expression of LDLr, SREBP-2 was detected by Immunohistochemical technique; the contents of IL-1β, TGF-β1 in supernatant were detected by ELISA.Results The lipid deposition in the group of IgA nephropathy(IgAN)presented with nephritic syndrome(NS) is significantly higher than the group of non-nephritic syndrome and normal children (P<0.05); the mRNA and protein expression in nephritic group are also significantly higher than that of non-nephritic and normal children group (P<0.05); the contents of IL-1β, TGF-β1 in supernatant cultured with 24h in the group of IgAN presented with NS is higher than that of non-nephritic and normal children group (P<0.05); there is no significant difference between group of non-nephritic syndrome and normal children (P>0.05).Conclusion Serum of IgAN with NS could cause abundent lipid deposition in HMC. It may stimulates mesangial cell to secrete inflammatory factors, such as IL-1βand TGF-β1, breaks off the feedback control system of SCAP-SREBPs-LDLr, and makes the expressions of SREBP-2 and LDLr up regulated, which results in abundent lipid was absorbed and deposited in the cell. PART THREE: THE ROLE OF SREBP-2-LDLR PATHWAY IN LIPID DEPOSITION IN KIDNEY OF IgAN IN CHILDRENObjective Comparing the expression situation of apoB100,LDLr and SREBP-2 in IgAN patient children'kidneys of different clinical types, to find out the clinical types which tend to lipid deposition, and to study the relationship between lipid deposition and SREBP-2-LDLr pathway.Methods The kidney tissue specimens of 11 cases of IgAN presented with nephritic syndrome(NS), 32 cases of non-nephritic IgAN and 4 cases of the normal were collected, and the expressions of apoB100, LDLr, SREBP-2 in each group were detected by immunohistochemical method.Results The positive expression rate of apoB100 in nephritic IgAN group is higher than non-nephritic IgAN group and normal control. The expressions of LDLr, SREBP-2 in cases of apoB100 positivity were higher the cases of apoB100 negativity. The expression of LDLr, SREBP-2 and apoB100 was significantly and positively correlated(r=0.671,r=0.562,P <0.05).Conclusion IgA nephropathy presented with nephritic syndrome more tend to lipid deposition in kidney than non-nephritic IgAN. It may make the expression of SREBP-2-LDLr up regulated, which results in abundent lipid was absorbed and deposited in the kidney tissue.