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Correlation between the Expression of High Mobility Group Box 1 and it Ligand Receptor for Advanced Glycation Endproducts in Lupus Nephritis

Author: YiHua
Tutor: LiBiJuan
School: Central South University
Course: Internal Medicine
Keywords: Lupus nephritis HMGB1 RAGE MCP-1
CLC: R593.242
Type: Master's thesis
Year: 2011
Downloads: 24
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Abstract

Objective:Systemic lupus erythematosus (SLE) is a kind of systemic autoimmune diseases involving multiple systems and organs,and the kidney lesions is the most common. Almost all patients with SLE have kidney pathological change, but there are only about 75% perform clinical behavior. There is something relevant between inflammatory reaction caused by immune complex and occurrence and development of the kidney lesion. And some of cytokines involved. Lots of research thought that Lupus nephritis (LN) was associated with high mobility group box 1 (HMGB1).As one of receptor of HMGB1, receptor for advanced glycation endproducts (RAGE) is relevant with inflammation response of LN. The renal biopsy is the gold standard to the diagnosis in lupus nephritis. But it’s a virulence operation, which could cause a series of complications like hematuresis, perirenal hematoma, infection, and the kidney lacerated wound, that are not widely accepted by patients. The clinical common methods of inspection, such as routine urine, total urine protein ration of 24 hours and creatinine clearance rate, can only distinguish obviously damaged kidneys but not early static changes. These limitations make a considerable portion of patient delay the best opportunity for treatment. This study through observe the expression changes of HMGB1, RAGE and its downstream factor monocyte chemoattactant protein 1(MCP-1), disused the mechanism of HMGB1 and RAGE in LN, to provide new experimental strategies to LN. Methods:Samples of peripheral blood were obtained from 83 patients with SLE who had hospitalized in Xiangya Hospital from September 2010 to January 2011,including 17 patients without LN,46 patients with LN. The control samples were obtained from 20 healthy volunteers.The choose of All SLE patients were conformed to the 1987 revised diagnostic criteria formulated by the American College of Rheumatology(ACR),and all into the group were no smoking history, malignant tumors or infectious diseases. Enzyme linked immunosorbent assay(ELISA)was used to detect serum concentration of HMGB1,MCP-1 and Neopterin(Npt).Reverse transcriptase-polymerse chain reaction (RT-PCR)was adopted to detect the expression of RAGEmRNA in the peripheral blood mononuclear cell(PBMC).Meanwhile, the related clinical and lab indexes were recorded.Results:1.Expression of RAGE in the peripheral blood of patients with LN:(1)The changes of RAGEmRNA detected by RT-PCR in PBMC RT-PCR showed that expression of RAGEmRNA on PBMC were higher in patients with LN than those with SLE and healthy people. There was no statistically significant difference between SLE group and control group.2. Expression of HMGB1 in the peripheral blood.The level of HMGB 1 in serum was higher in patients with LN [(257.69士68.87)ng/ ml]than those with SLE[(180.81士35.05)ng/ml] (P<0.01) and healthy people[(151.27士35.91)ng/ml](P<0.01); There was no statistically significant difference between SLE group and control group. 3.Expression of NPT in the peripheral blood.The level of Npt proteins in serum was higher in patients with LN [(215.66士41.65)ng/ ml]and SLE [(196.80士36.19)ng/ml] than healthy people[(119.61士26.84)ng/ml](P<0.01); There was no statistically significant difference between LN group and SLE group.4. Expression of MCP-1 in the peripheral blood.The level of MCP-1 in serum was higher in patients with LN[(4387.41士605.72)pg/ ml] and SLE [(4243.94士578.40)pg/ml] than healthy people[2118.97士358.77)pg/ml](P<0.01); There was no statistically significant difference between LN group and SLE group.5. Level of HMGB 1 protein in serum of SLE was both negatively correlated with the hemoglobin and negatively correlated with the albumen. Level of RAGE mRNA in PBMC was both negatively correlated with the hemoglobin,and negatively correlated with the albumen.Conclusions:Level of HMGB 1 protein、RAGE mRNA in serum of LN patients was higher in patients with LN than those without LN and healthy people. That was also negatively correlated with the level of Hemoglobin and albumen. These revealed that HMGB 1 and RAGE were important cytokines in LN. And they may become some of the indicators in laboratory diagnosis in LN.

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CLC: > Medicine, health > Internal Medicine > Systemic disease > Autoimmune diseases > Autoimmune diseases, connective tissue disease > Lupus erythematosus > Lupus nephritis
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