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Low-molecular-weight fucoidan and effect thereof on diabetic nephropathy

A technology of molecular fucoidan sulfate and fucoidan sulfate, which is applied in the field of low molecular weight fucoidan sulfate and its effect on diabetic nephropathy, can solve problems such as hypoglycemia and difficult control of DN-inducing factors

Inactive Publication Date: 2014-05-21
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because DN-inducing factors are often difficult to control and can easily lead to serious consequences such as hypoglycemia, how to block a key link in the pathogenesis of DN to achieve twice the result with half the effort has become a hot research topic at present.

Method used

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  • Low-molecular-weight fucoidan and effect thereof on diabetic nephropathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: Degradation and separation and purification of low molecular weight fucoidan sulfate

[0019] (1) Take fucoidan sulfate (undegraded) and degrade it with hydrochloric acid, the concentration of hydrochloric acid is 0.1mol / L, the degradation temperature is 60°C, and the degradation time is 18 hours;

[0020] (2) After the above-mentioned acid is degraded, it is roughly separated by an ultrafiltration membrane with a molecular weight cut-off of 6000Da to obtain LMWF of <6000Da;

[0021] (3) The above-mentioned LMWF 1 H NMR and 13 C NMR results show that LMWF-2-3 is composed of α-configuration pyranose, the monosaccharide component is mainly fucose, and there is 4-OSO 3 - ; The structure of LMWF-2-3 is thus deduced as figure 1 shown.

Embodiment 2

[0022] Example 2: Protective effect of low molecular weight fucoidan sulfate on rats with diabetic nephropathy

[0023] The right kidney of the rat was removed, and DN model was established by intraperitoneal injection of streptozotocin at a dose of 45 mg·kg-1 two weeks later. DN rats were randomly divided into DN model group, positive control Val group (20mg / kg / d), positive control fucoidan sulfate (undegraded) group (240mg / kg / d), low molecular weight fucoidan Sulfate (that is, LMWF-2-3 prepared in Example 1, the same below) high-dose group (240mg / kg / d), low-molecular-weight fucoidan sulfate medium-dose group 1 (120mg / kg / d) and low-dose Molecular fucoidan sulfate low-dose group (60mg / kg / d), and set up a sham operation control group. After 8 weeks of the experiment, the renal function of DN rats (UAE, BUN, Cr) was detected, and the serum TGF-β of DN rats was measured by ELISA 1 The content of kidney TGF-β was determined by immunohistochemical method 1 and Col-Ⅳ in situ expr...

Embodiment 3

[0024] Example 3: Effect of low molecular weight fucoidan sulfate on mesangial cells cultured in vitro with high glucose

[0025] Rat mesangial cells cultured in vitro: divided into normal control group; high glucose injury model group; Val (2×10 -5 mol L -1 , 2×10 -6 mol L -1 , 2×10 -7 mol L -1 ) treatment group; low-molecular-weight fucoidan sulfate high-dose group (500 μg / ml), low-molecular-weight fucoidan sulfate medium-dose group (50 μg / ml), low-molecular-weight fucoidan sulfate low-dose group ( 5 μg / ml). MTT method was used to observe the effect of drugs on its proliferation, and ELISA method was used to detect the secretion of TGF-β by mesangial cells 1 The content of Col-Ⅳ expressed in mesangial cells was detected by immunohistochemical method. The results show that low molecular weight fucoidan sulfate can significantly inhibit the proliferation of mesangial cells and inhibit TGF-β 1 Over-secretion and over-expression of Col-Ⅳ, each administration group can sh...

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Abstract

The invention discloses a process for preparing low-molecular-weight fucoidan, wherein the low-molecular-weight fucoidan is prepared through the process steps of hydrochloric acid degradation, desalination, ion exchange column elution and the like. Proved by pharmacological activity experiments, the low-molecular-weight fucoidan prepared by adopting the method disclosed by the invention is capable of obviously improving renal function, reducing proteinuria, slowing glomerular sclerosis and playing a role of protecting kidney. Proved by animal experiments, the effect of the low-molecular-weight fucoidan is obviously better than that of fucoidan with the same dose, so that the low-molecular-weight fucoidan disclosed by the invention can be used for preparing drugs for treating diabetic nephropathy or can be directly used as a drug for treating the diabetic nephropathy.

Description

technical field [0001] The invention relates to low-molecular-weight fucoidan sulfate and its effect on diabetic nephropathy, belonging to the field of marine medicine. Background technique [0002] Diabetic nephropathy (DN) is the most common complication of diabetes (DM) and the main cause of end stage renal disease (ESRD). The pathogenesis of DN is extremely complicated. The expression of angiotensin Ⅱ (angiotensin Ⅱ, Ang Ⅱ) in the local kidney increases in DM, which causes a series of cytokine disorders in the body and promotes the occurrence and development of DN. transforming growth factor beta 1 (transforming growth factor-beta1, TGF-β 1 ) is considered to have pro-sclerotic properties and is a major contributor to diabetic glomerulosclerosis. Type Ⅳ collagen (Col-Ⅳ), as one of the main components of ECM (extracellular matrix: extracellular matrix), is the main index to measure the accumulation of ECM, and plays an important role in the pathogenesis of DN. [0003...

Claims

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Application Information

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IPC IPC(8): C08B37/00A61K31/715A61P3/10A61P13/12
Inventor 吉爱国宋淑亮梁浩王秀敏
Owner SHANDONG UNIV
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