阅读说明：本技术 Gmfb作为糖尿病肾病的生物标记物的应用 (Application of GMFB (GMFB) as biomarker of diabetic nephropathy ) 是由 吕立夏 徐国彤 朱彤 龚浩宇 邱天羽 于 2019-04-04 设计创作，主要内容包括：本发明提供了一种GMFB作为糖尿病肾病的生物标记物的应用。本发明实验发现：GMFB在早期糖尿病大鼠的肾小管上皮细胞中表达,而在正常大鼠的肾小管上皮细胞中不表达。相比正常STZ诱导2周的TIDM大鼠,GMFB敲除的STZ诱导2周的T1DM大鼠在链脲霉素腹腔注射诱导下的肾病早期相关标记物Kim-1、MCP-1、IL-1beta的mRNA表达量显著降低,说明敲除GMFB能在早期阻断糖尿病肾病的发病,避免糖尿病肾病产生。(the invention provides application of GMFB as a biomarker of diabetic nephropathy. The experiment of the invention finds that: GMFB is expressed in tubular epithelial cells of early diabetic rats, but not in tubular epithelial cells of normal rats. Compared with a normal TIDM rat induced by STZ for 2 weeks, the mRNA expression level of early nephropathy related markers Kim-1, MCP-1 and IL-1beta of a GMFB knockout STZ induced T1DM rat induced by 2 weeks under streptozotocin intraperitoneal injection induction is obviously reduced, which indicates that the GMFB knockout can block the onset of diabetic nephropathy at the early stage and avoid the generation of diabetic nephropathy.)

Use of GMFB as a biomarker for diabetic nephropathy.

Application of GMFB as a biomarker in preparation of a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy.

3. The application of the reagent for detecting the GMFB expression level in the preparation of a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy.

The application of the GMFB interfering agent in the preparation of the drugs for preventing, improving or treating diabetic nephropathy, wherein the GMFB interfering agent is a substance that interferes the GMFB activity or down-regulates the GMFB expression.

Technical Field

The invention belongs to the technical field of biological detection and biological medicine, and particularly relates to application of GMFB as a biomarker of diabetic nephropathy.

Background

With the rapid development of economy and the acceleration of aging process in China, the prevalence rate of Diabetes Mellitus (DM) is on the rapid rising trend, and the DM becomes another important chronic non-infectious disease which seriously harms the health of people after cardiovascular and cerebrovascular diseases and tumors. The world health organization speculates that in 2025, chinese diabetics will reach 3 billion. Diabetic nephropathy is one of the most important complications of diabetic patients, the incidence rate of the diabetic nephropathy in China is on the rise, and the diabetic nephropathy becomes the second cause of end-stage nephropathy at present and is second to various glomerulonephritis. Diabetic nephropathy has complex metabolic disorders, and once the diabetic nephropathy develops to end-stage nephropathy, the treatment of the diabetic nephropathy is more troublesome than the treatment of other kidney diseases, so that the timely prevention and treatment of the diabetic nephropathy has great significance for delaying the diabetic nephropathy. The etiology and pathogenesis of diabetic nephropathy are unclear. At present, the disease is caused by the participation of multiple factors under the combined action of certain genetic background and partial risk factors. Kim-1(van Timmen M, Mc V D H, Baily V, et al. tubular kit in jet patient-1 (KIM-1) in human residual disease. journal of Pathology,2007,212(2):209-17.), MCP-1(Haller H, Bertram A, Nadrowitz F, Menne J. monoclonal chemoattractant protein-1 and the kit. Current Optin protein-2016; 25(1):42-9.), IL-1b (Moreno JA, Gomemez-Guerrec, Mas S, et al. target in diabetes patient. beta. trial: expression of diabetes 917) was considered to be a directly involved in the development of diabetic nephropathy (diabetes mellitus) (33. 11. multidrug) in which diabetes mellitus was identified as a marker).

Glial cell maturation factor beta (GMFB), which was originally a 17kd acidic cytoplasmic protein isolated and purified from bovine brain, was highly conserved evolutionarily, produced mainly by astrocytes in the central nervous system, and had important effects on growth, differentiation and regeneration of brain tissue, with its expression being up-regulated during the developmental stage and significantly reduced in adulthood. Recent studies have shown that GMFB is a pro-inflammatory factor, closely related to degenerative diseases of the human central nervous system, such as alzheimer's disease and parkinson's disease; GMFB knockout mice are able to resist the toxicity of experimental autoimmune encephalitis and MPTP.

disclosure of Invention

In view of the state of the art in the background, it is an object of the present invention to provide the use of GMFB as a biomarker for diabetic nephropathy.

The invention provides application of GMFB as a biomarker of diabetic nephropathy.

The invention provides application of GMFB as a biomarker in preparation of a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy.

The invention provides an application of a reagent for detecting GMFB expression level in preparing a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy.

the invention provides application of a GMFB (GMFB) interfering agent in preparation of a medicament for preventing, improving or treating diabetic nephropathy, wherein the GMFB interfering agent is a substance interfering GMFB activity or down-regulating GMFB expression.

has the advantages that: the invention provides the use of GMFB as a biomarker for diabetic nephropathy. The research of the invention finds that: GMFB is expressed in tubular epithelial cells of early diabetic rats, but not in tubular epithelial cells of normal rats. Compared with a normal TIDM rat induced by STZ for 2 weeks, the mRNA expression level of early nephropathy related markers Kim-1, MCP-1 and IL-1beta of a GMFB knockout STZ induced T1DM rat induced by 2 weeks under streptozotocin intraperitoneal injection induction is obviously reduced, which indicates that the GMFB knockout can block the onset of diabetic nephropathy at the early stage and avoid the generation of diabetic nephropathy.

drawings

FIG. 1 shows the change in the expression level of Kim-1 in example 2 of the present invention;

FIG. 2 shows the expression level of MCP-1 of example 2 of the present invention;

FIG. 3 shows the expression level of IL-1. beta. according to example 2 of the present invention;

FIG. 4 is a microscope photograph of example 3 of the present invention.

Detailed Description

The invention provides application of GMFB as a biomarker of diabetic nephropathy. Preferably, the application comprises the preparation of a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy by using GMFB as a biomarker. The invention can detect that the expression of GMFB is obviously increased in the kidney of 1 week of the onset of type I diabetes, and is earlier than the expressions of MCP-1, IL-1beta and kim-1; can be used as a marker of early diabetic nephropathy.

the invention provides an application of a reagent for detecting GMFB expression level in preparing a reagent or a kit for early diagnosis and disease course progression of diabetic nephropathy. In the present invention, the reagent for detecting the expression level of GMFB preferably comprises a reagent for detecting the expression level of mRNA of GMFB in kidney. In view of the relationship between the GMFB expression level and the early diagnosis and the disease course progression of the diabetic nephropathy, the reagent for detecting the GMFB expression level has good application prospect when being applied to the preparation of the reagent or the kit for the early diagnosis and the disease course progression of the diabetic nephropathy.

the invention also provides application of the GMFB interfering agent in preparation of a medicament for preventing, improving or treating diabetic nephropathy. In the present invention, the GMFB interfering agent is a substance that interferes with GMFB activity or down-regulates GMFB expression. In view of the relationship between the GMFB expression level and the early diagnosis and the disease course progression of the diabetic nephropathy, the GMFB interfering agent has wide prospect in being applied to the drugs for preventing, improving or treating the diabetic nephropathy.

The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.