Angptl4在人足细胞损伤相关疾病中的作用研究
发布时间：2019-06-29 20:24
【摘要】：研究背景：膜性肾病(MN, membranous nephropathy)和微小病变性肾病(MCN, minimal change nephropathy)分别是成人和儿童肾病综合征中最常见的病理类型,它们临床上都是以大量蛋白尿、低白蛋白血症、水肿和高脂血症为主要特点,病理改变上两者都会发生足突细胞的融合,同时也有各自特征性的改变。长期大量蛋白尿对肾病患者的预后具有极大的影响,近年来,以MCD大鼠为研究对象的研究发现：与肾病综合征其他病理类型相比, MCD大鼠肾组织中血管生成素样蛋白-4(Angpt14, Angiopoietin-like4)的表达明显升高。 目的：通过对比分析足细胞损伤肾病综合征患者、足细胞损伤非肾病综合征患者、IgA肾病患者和正常健康对照者的血浆、尿液和肾组织石蜡切片中Angpt14的表达特点及差异。 实验方法：实验分四组,分别为足细胞损伤肾病综合征组(NS组,nephrotic syndrome group)72例、足细胞损伤非肾病综合征组(non-NS组)64例、IgA肾病组(IgAN组,IgA nephropathy group)37例和健康对照组60例(Con组,healthy control group),收集四组个体的血浆、尿液和肾组织石蜡切片标本,运用酶联免疫吸附剂测定法(ELISA, enzyme linked immunosorbent assay)测定Angpt14蛋白的表达情况,并用方差分析(Analysis of Variance)进行数据分析。应用免疫组化测定肾活检组织石蜡切片中Angptl4蛋白的表达情况。 结果：血浆中,NS组、non-NS组、IgAN组和Control组之间Angptl4OD值比较,结果除NS组与non-NS组之间没有差异外,其余两两之间均有显著差异(NS:1.296±0.634; non-NS:1.469±0.546; IgAN:1.731±0.387; Control:2.142±0.416),比较IgAN组中尿蛋白肌酐比值不同的三组患者(0-0.5g/g vs0.5-3.5g/g vs3.5-g/g)的血浆Angpt140D值发现,三者之间有差异(1.875±0.381vs1.694±0.324vs1.016±0.098).同样对non-NS组中尿蛋白肌酐比值不同的两组患者和NS组进行了比较(0-0.5g/g vs0.5-3.5g/g vs NS组),三者之间没有显著差异。应用线性相关分析发现NS组中血浆Angpt14OD值与患者尿蛋白肌酐比值、尿蛋白浓度、GFR以及Scr之间均没有显著相关关系。IgAN组中血浆Angpt14与尿蛋白肌酐和尿蛋白浓度有线性相关关系。分析non-NS组,发现血浆Angpt14OD值与患者尿蛋白浓度之间呈负相关关系。 尿液中,NS组、non-NS组、IgAN组和Control组之间Angpt14OD值比较显示两两之间均有显著差异(NS:2.830±0.340; non-NS组：2.456±0.770; IgAN:1.569±0.810; Control:0.163±0.270)。比较IgA组中尿蛋白肌酐比值不同的三组患者(0-0.5g/g vs0.5-3.5g/g vs3.5-g/g)的尿液Angptl4OD值发现,两者之间没有显著差异。同样对non-NS组中尿蛋白肌酐比值不同的两组患者与NS组进行了比较(0-0.5g/g vs0.5-3.5g/g vs NS组),发现两两之间均有显著差异(1.150±0.086vs2.537±0.717vs2.830±0.340).线性相关分析发现NS组中尿液Angpt14OD值与患者尿蛋白肌酐比值、尿蛋白浓度、GFR以及Scr之间均没有显著相关关系。IgAN组中发现尿液Angpt14的OD值与尿蛋白肌酐比值以及尿蛋白浓度均呈正相关。分析non-NS组,发现尿液Angpt14OD值与患者尿蛋白肌酐比值之间也呈正相关关系。 免疫组化结果显示,NS组和non-NS组的足细胞均有阳性染色,IgAN组和Control组肾小球足细胞均为阴性,其中NS组的阳性染色高于non-NS组。 结论：足细胞损伤肾病综合征患者、足细胞损伤非肾病综合征患者、IgA肾病患者和正常健康对照者(两两之间)的血浆、尿液和肾组织Angptl4的表达有差异。Angpt14在足细胞损伤患者,尤其是肾病综合征患者中有特异性表达,尿液中Angpt14蛋白的差异可以反映足细胞损伤程度的差异。该蛋白在足细胞损伤的病理生理过程中有重要作用。
[Abstract]:Background: The most common pathological types in adult and children's nephrotic syndrome are membranous nephropathy (MN, mbinous nephron) and micro-pathological renal disease (MCN, minimbal change nephron), which are mainly characterized by a large amount of proteinuria, hypoalbuminemia, edema and hyperlipidemia. The fusion of the apophysis cells can occur both in the pathological change and the characteristic changes. In recent years, the expression of angiopoietin-like protein-4 (Angpt14, Angiopoietin-like4) in the kidney of the MCD was significantly increased compared with the other pathological types of the nephrotic syndrome. Objective: To compare the expression and difference of Angpt14 in serum, urine and renal tissue paraffin sections of patients with nephrotic syndrome, diabetic nephropathy and normal healthy controls. Methods: The experimental methods were divided into four groups: group NS group, nephrastic syndrome group (72 cases), foot cell injury non-nephrotic syndrome group (non-NS group)64 cases, IgA nephropathy group (IgAN group, IgA nephron group)37 cases and healthy control group 60 cases (Con group, healthy control gro). Up), blood plasma, urine and kidney tissue paraffin section specimens of four groups were collected, and the expression of the Angpt14 protein was determined by an enzyme-linked immunosorbent assay (ELISA, enzyme linked immunosorbent assay) and the number of analysis of variance was used to count the expression of the Angpt14 protein. An immunohistochemical method for the determination of Angptl4 protein in paraffin section of renal biopsy tissue As a result, the Angptl4OD values between the NS group, the non-NS group, the IgAN group and the Control group were compared, and there was no difference between the NS group and the non-NS group, and there was a significant difference between the other two groups (NS: 1.296-0.634; non-NS: 1.469-0.546; IgAN: 1.731-0.387; Control: 2.142-0 .416) The plasma Angpt140D values of three groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgAN group were found to be different (1.875) 0.381 vs1.694 and 0.324 vs1.016-0 in comparison with the plasma Angpt140D values of the different groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgAN group. .0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group) were also compared in two groups of patients and NS groups with different urinary protein levels in the non-NS group (0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group). There was a significant difference. There was no significant difference in the ratio of Angpt14OD in the NS group to the ratio of the patient's urinary protein, the concentration of urinary protein, the GFR, and the Scr in the NS group. The relationship between plasma Angpt14 and urinary protein and urinary protein concentration in the IgAN group The relationship between plasma Angpt14OD and urinary protein concentration was found in non-NS group. There were significant differences in the Angpt14OD between the NS group, the non-NS group, the IgAN group and the Control group (NS: 2.830-0.340; non-NS group: 2.456-0.770; IgAN: 1.569-0.810; Control: 0.163 (0.270) The urine Angptl4OD values of three groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgA group were found to be different from those in the IgA group, both of which There was no significant difference between the two groups (0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group) in the non-NS group, and there was a significant difference between the two groups (1.150, 0.086 vs2.537) 0.717 vs2.830 (0.340). The linear correlation analysis found that the urine Angpt14OD value in the NS group was not related to the ratio of the urinary protein of the patient, the concentration of the urinary protein, the GFR, and the Scr. There was a significant correlation. In the IgAN group, the ratio of OD value of the urine Angpt14 to the urinary protein muscle and the urinary protein were found in the IgAN group. The concentrations were positively correlated. The non-NS group was analyzed to find the ratio of Angpt14OD of urine to the ratio of urinary protein in the patient. The positive staining was positive in both the NS group and the non-NS group. The positive staining of the NS group was negative. Higher than non-NS group. Conclusion: The plasma, urine and renal tissue An in the patients with diabetic nephrotic syndrome, patients with foot cell injury, non-nephrotic syndrome, patients with IgA nephropathy and normal healthy controls (between two) The expression of gtl4 is different. Angpt14 is specifically expressed in patients with foot cell injury, especially in nephrotic syndrome, and the difference of Angpt14 protein in urine can be reversed. The difference of the degree of damage to the foot cell. The protein is in the disease of the foot cell.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692
本文编号：2508086
[Abstract]:Background: The most common pathological types in adult and children's nephrotic syndrome are membranous nephropathy (MN, mbinous nephron) and micro-pathological renal disease (MCN, minimbal change nephron), which are mainly characterized by a large amount of proteinuria, hypoalbuminemia, edema and hyperlipidemia. The fusion of the apophysis cells can occur both in the pathological change and the characteristic changes. In recent years, the expression of angiopoietin-like protein-4 (Angpt14, Angiopoietin-like4) in the kidney of the MCD was significantly increased compared with the other pathological types of the nephrotic syndrome. Objective: To compare the expression and difference of Angpt14 in serum, urine and renal tissue paraffin sections of patients with nephrotic syndrome, diabetic nephropathy and normal healthy controls. Methods: The experimental methods were divided into four groups: group NS group, nephrastic syndrome group (72 cases), foot cell injury non-nephrotic syndrome group (non-NS group)64 cases, IgA nephropathy group (IgAN group, IgA nephron group)37 cases and healthy control group 60 cases (Con group, healthy control gro). Up), blood plasma, urine and kidney tissue paraffin section specimens of four groups were collected, and the expression of the Angpt14 protein was determined by an enzyme-linked immunosorbent assay (ELISA, enzyme linked immunosorbent assay) and the number of analysis of variance was used to count the expression of the Angpt14 protein. An immunohistochemical method for the determination of Angptl4 protein in paraffin section of renal biopsy tissue As a result, the Angptl4OD values between the NS group, the non-NS group, the IgAN group and the Control group were compared, and there was no difference between the NS group and the non-NS group, and there was a significant difference between the other two groups (NS: 1.296-0.634; non-NS: 1.469-0.546; IgAN: 1.731-0.387; Control: 2.142-0 .416) The plasma Angpt140D values of three groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgAN group were found to be different (1.875) 0.381 vs1.694 and 0.324 vs1.016-0 in comparison with the plasma Angpt140D values of the different groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgAN group. .0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group) were also compared in two groups of patients and NS groups with different urinary protein levels in the non-NS group (0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group). There was a significant difference. There was no significant difference in the ratio of Angpt14OD in the NS group to the ratio of the patient's urinary protein, the concentration of urinary protein, the GFR, and the Scr in the NS group. The relationship between plasma Angpt14 and urinary protein and urinary protein concentration in the IgAN group The relationship between plasma Angpt14OD and urinary protein concentration was found in non-NS group. There were significant differences in the Angpt14OD between the NS group, the non-NS group, the IgAN group and the Control group (NS: 2.830-0.340; non-NS group: 2.456-0.770; IgAN: 1.569-0.810; Control: 0.163 (0.270) The urine Angptl4OD values of three groups of patients (0-0.5 g/ g vs0.5-3.5 g/ g vs3.5-g/ g) in the IgA group were found to be different from those in the IgA group, both of which There was no significant difference between the two groups (0-0.5 g/ g vs0.5-3.5 g/ g vs. NS group) in the non-NS group, and there was a significant difference between the two groups (1.150, 0.086 vs2.537) 0.717 vs2.830 (0.340). The linear correlation analysis found that the urine Angpt14OD value in the NS group was not related to the ratio of the urinary protein of the patient, the concentration of the urinary protein, the GFR, and the Scr. There was a significant correlation. In the IgAN group, the ratio of OD value of the urine Angpt14 to the urinary protein muscle and the urinary protein were found in the IgAN group. The concentrations were positively correlated. The non-NS group was analyzed to find the ratio of Angpt14OD of urine to the ratio of urinary protein in the patient. The positive staining was positive in both the NS group and the non-NS group. The positive staining of the NS group was negative. Higher than non-NS group. Conclusion: The plasma, urine and renal tissue An in the patients with diabetic nephrotic syndrome, patients with foot cell injury, non-nephrotic syndrome, patients with IgA nephropathy and normal healthy controls (between two) The expression of gtl4 is different. Angpt14 is specifically expressed in patients with foot cell injury, especially in nephrotic syndrome, and the difference of Angpt14 protein in urine can be reversed. The difference of the degree of damage to the foot cell. The protein is in the disease of the foot cell.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692
【共引文献】
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