CN107028938B - Application of lipoamide in preparing composition for delaying and treating diabetic nephropathy - Google Patents
Application of lipoamide in preparing composition for delaying and treating diabetic nephropathy Download PDFInfo
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Abstract
The invention discloses an application of lipoamide in preparing a composition for delaying and treating diabetic renal complications.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of lipoamide in delaying and treating diabetic nephropathy.
Background
The incidence of diabetes is increasing continuously, and the incidence of diabetic nephropathy, one of the serious complications of diabetes, is also increasing year by year, and has become one of the main causes of chronic renal failure and the leading cause of death from diabetes. Diabetic nephropathy is complicated by approximately 30% of type 1 diabetic patients and 25% to 40% of type 2 diabetic patients. However, the pathogenesis of diabetic nephropathy is very complex, and the current research results suggest that various factors such as metabolic disorder, hemodynamic changes, inflammatory response mechanism, cytokines, oxidative stress, genetic factors, kinin system and autophagy participate in the pathogenesis of diabetic nephropathy, but the exact mechanism of the pathogenesis is not clear, so that the treatment of diabetic nephropathy is a very difficult medical problem and an effective treatment medicine is lacked. The traditional treatment thought mainly focuses on controlling peripheral risk factors such as blood sugar, blood pressure, blood fat and the like, but the treatment effect is not ideal. Therefore, finding an effective method for preventing and stopping the progressive decline of the renal function and delaying and treating the diabetic nephropathy becomes an inexhaustible task for preventing and treating the diabetic nephropathy at present.
The pathogenesis and pathological manifestations of diabetic nephropathy are complex, and mainly include glomerulosclerosis and tubulointerstitial fibrosis. Tubulointerstitial fibrosis is manifested by replacement of the normal tubular and interstitial structures of the kidney by a large amount of aggregated extracellular matrix (ECM), with myofibroblasts appearing in the interstitium. While tubular epithelial cells (RTECs) are the major renal parenchymal cells, transdifferentiation (EMT) of tubular epithelial cells to myofibroblasts occurs. Myofibroblasts have a strong ability to secrete ECM, and at the same time release enzymes that inhibit ECM breakdown, resulting in reduced ECM breakdown and accumulation, which directly leads to interstitial fibrosis and impairment of renal function.
Transforming growth factor β (TGF- β 1) is recognized as a key causative factor in the development of tissue fibrosis in diabetic nephropathy, and plays an important role in the development of progressive lesions in diabetic nephropathy through the downstream spring/threonine kinase receptor (Smad) signaling pathway1Smads protein interaction downstream of signaling, negatively regulating TGF- β1And the signal path plays a role in blocking the fibrosis process. The inventor has studied the change of SnoN expression in the process of diabetic nephropathy (china pathophysiology journal, 2008, 24 vol. 6, 1188 page), and found that SnoN expression is reduced along with the progress of diabetic nephropathy, and the high sugar stimulation can cause the reduction of SnoN protein expression of rat primary tubular epithelial cells and is time-dependent, which indicates that the reduction of SnoN protein level expression is an important pathogenesis of diabetic nephropathy renal fibrosis. Therefore, the increase of the expression of SnoN by means of medicines and the like is very important for the intervention of the renal fibrosis process of diabetic nephropathy. But currently the use of drugs in this area is very limited.
On the other hand, if the stability of the SnoN protein can be increased by the action of the drug, it may be helpful to intervene in the fibrosis process of diabetic nephropathy. However, no intervention of the drug on the stability of SnoN protein and further on the effect on renal fibrosis has been reported so far.
It is also regulated by transforming growth factor beta-activated kinase (TAK-1) (J Biol chem.2007 Vol.13, page 9475). TAK1 is one of the members of the Mitogen-Activated Protein Kinase (MAPKK) family, and is Activated by phosphorylation by TGF-. beta.1. Previous researches show that the expression and activity of TAK1mRNA and protein are increased along with the progress of pathological damage of the kidney, and the phenotypic transformation of renal tubular epithelium can be mediated. While the use of TAK1 inhibitors in the treatment of db/db mice results in a significant reduction in urinary protein, reduction in pathological changes, reduction in macrophage infiltration, and the like. However, the prior art reports neither the relationship between the stability of the SnoN protein and the occurrence of transdifferentiation (EMT) of renal tubular epithelial cells into myofibroblasts nor the relationship
Alpha-lipoic acid is a fat-soluble structure containing disulfide five-membered rings, has high electron density, electrophilicity and the capability of reacting with free radicals, and therefore has remarkable oxidation resistance. Is clinically used for treating the paraesthesia caused by diabetic peripheral neuropathy. In intervention and treatment of diabetic nephropathy, influence of lipoic acid on clinical curative effect of early diabetic nephropathy is reported frugal in 2015 (Chinese practical medicine, 2015, volume 10, phase 6, page 143), and when a patient is treated by metformin, lipoic acid capsules are administered for 28 days continuously, so that the effect of reducing excretion rate of urine microalbumin can be achieved, and the effect of treating early diabetic nephropathy is remarkable. In 2011, a study on the influence of lipoic acid on renal fibrosis of a diabetic nephropathy rat is reported by royal jelly and the like (a journal of Liaoning medical college, 2011, 32 vol.6 and 489 pages), and the lipoic acid is continuously administrated by gastric lavage for 12 weeks, and the result shows that the lipoic acid can play a role in resisting fibrosis by inhibiting the expression of renal tissue TGF-beta 1 and the like, so that the development of renal fibrosis of the STZ diabetic rat is delayed. However, lipoic acid is not an important drug for the treatment of diabetic nephropathy because the intervention and protection effects of lipoic acid on diabetic nephropathy are not prominent enough. The current intervention mechanism research of the lipoic acid on the diabetic nephropathy focuses on an antioxidant mechanism, and the research on whether other action mechanisms intervening in the diabetic nephropathy exist in the medicine is less.
Lipoamide (Lipoamide), a derivative of alpha-lipoic acid.
Lipoamide can scavenge free radicals in vivo and promote the generation of endogenous antioxidants, and has attracted the interest of researchers due to its high-efficiency antioxidant effect. Li et al found that lipoamide can protect retinal pigment epithelial cells by inhibiting oxidative stress and improving mitochondrial function (Free Radic Biol Med.2008, Vol. 44, p. 1465). Zhao et al found that lipoamide can exert indirect antioxidant effect by activating mitochondrial regeneration and phase II antioxidant enzymes (PLoSOne.2015 Vol 10, e 0128502). The lipoamide is sold in the market abroad as a liver protection medicament, but reports of the lipoamide on the drug effect of delaying and treating diabetic nephropathy and research on the action mechanism of the lipoamide are not seen.
Disclosure of Invention
The invention aims to provide the application of lipoamide in delaying and treating diabetic nephropathy.
The lipoamide of the invention is used for preparing a composition for delaying and treating diabetic renal complications.
The lipoamide of the invention is used for preparing a composition for improving renal fibrosis lesion and improving the renal function and metabolism of rats.
The lipoamide of the invention is used for preparing a composition for reducing the kidney weight/body weight ratio, 24h urine protein, total cholesterol and triglyceride of a diabetic rat.
The lipoamide provided by the invention is used for preparing a composition for inhibiting the effect of renal tissue oxidative stress of a diabetic rat, recovering the activity of Total antioxidant capacity (T-AOC), Total superoxide Dismutase (T-SOD) and Catalase (CAT) of the renal tissue and obviously reducing the level of Malondialdehyde (MDA) of the renal tissue.
The lipoamide of the invention is used for preparing the composition which reduces the expression of renal interstitial Collagen I (Collagen I), plays a role in resisting diabetes and renal fibrosis and obviously improves renal fibrosis lesion.
The lipoamide provided by the invention is used for preparing a composition for promoting the expression level of a nuclear transcription co-inhibitory factor SnoN protein which is critically regulated and controlled by renal fibrosis.
The lipoamide of the invention is used for preparing a composition for reducing the ubiquitination level of a nuclear transcription co-inhibitory factor SnoN protein which is key regulated and controlled by renal fibrosis and improving the stability of the SnoN protein.
The optical enantiomer, hydrate, hydrogenated addition product or precursor of lipoamide has the same or similar functions of improving renal fibrosis lesion, improving renal function and metabolism of rats, and can delay and treat diabetic renal complications.
The hydrogenated adduct refers to a sulfhydryl compound formed by the ring opening of the disulfide bond hydrogenation in the structural formula (I); the term "precursor" refers to a compound or analog thereof that undergoes a metabolic or chemical reaction in a mammalian body to convert the compound to the structural formula (I).
The compositions of the present invention include pharmaceutical compositions and dietary supplements (e.g., nutraceutical compositions) so long as they contain lipoamide as an active ingredient for improving renal fibrotic changes, improving renal function and metabolism.
The lipoamide or the optical enantiomer, hydrate, hydrogenated adduct or precursor thereof is used for preparing a composition capable of improving renal fibrosis lesion and improving renal function and metabolism of rats.
The invention establishes an SD rat model of diabetic nephropathy, takes lipoic acid as a positive control, and perfuses and gives lipoamide and lipoic acid to rats. The results show that the lipoamide can obviously reduce the weight/weight ratio (KW/BW) of the kidney, Total Cholesterol (TC), Triglyceride (TG) and 24h urine protein (24h UP) of the diabetic rat after 6 weeks; the activities of the T-AOC, the T-SOD and the CAT are obviously higher than those of the DM group, the MDA level is obviously reduced, the activities of the T-AOC and the T-SOD of the lipoamide treatment group are more obviously recovered than those of the lipoic acid group, and the MDA level reduction is also more obviously than that of the lipoic acid group; h & E, Masson staining results show that the lipoamide group renal fibrosis lesion is obviously improved, and the expression of lipoamide group renal interstitial collagen I (collagen I) is obviously lower than that of the lipoic acid group; increased expression of the level of SnoN protein in the lipoamide treated group; ubiquitinated SnoN protein decreased, stability of SnoN protein increased, and expression and activation of transforming growth factor β activated kinase (TAK-1) were found to decrease. The results show that the lipoamide can improve the renal function and metabolism of rats and has the effect of increasing the expression level of snoN protein; meanwhile, the stability of the SnoN protein can be improved by inhibiting the expression and activation of TAK1, so that the expression of Collagen I is reduced to exert the effect of resisting diabetes mellitus and kidney fibrosis.
Detailed Description
The following experiments are conducted under conditions not specifically mentioned, and generally, the conditions are conventional in the art.
1. Material
Male Sprague-Dawley (SD) rats of healthy and clean grade, body weight (180. + -. 20) g, supplied by the Biotech corporation of Fukang, Beijing, Huafukang, under the batch number SCXK (Jing) 2009-. Steady-fold-addition glucometer (Qiangsheng corporation), ultra-low temperature refrigerator (Sanyo), high-speed low-temperature centrifuge (Beckman), Bayer1650 full-automatic biochemical analyzer (Beckman), electrophoresis system and electrotransfer device (Amersham), and gel imaging system (Bio-Rad). The positive control drug lipoic acid was purchased (sienna bang biotechnology limited); the test compound lipoamide was synthesized according to the following method.
The preparation method of lipoamide comprises the following steps: 30.0g of lipoic acid and 300mL of dichloromethane are added into a round-bottom flask, 20.8g of 1-hydroxybenzotriazole is added at room temperature after stirring and dissolving, 28g of dicyclohexylcarbodiimide is added in three batches after stirring for 0.5h, the reaction is stopped after stirring for 10h at room temperature, and the reaction solution is washed three times with water (150 mL/time), separated and concentrated to obtain 40 g of yellow solid. Dissolving 15.0g of the solid in 90mL of tetrahydrofuran, adding 40mL of concentrated ammonia water while stirring, stirring at room temperature for 8h, evaporating the organic solvent under reduced pressure, adding 50mL of water into the residue, stirring at room temperature for 2h, filtering, and drying the filter cake under reduced pressure at 40 ℃ to obtain a crude product of lipoamide. The crude product is recrystallized twice by ethanol to obtain lipoamide which is light yellow powdery solid, and the yield is 84.7 percent. Structural characterization data:1H NMR(d-DMSO，400MHz)，:7.21(s,1H)； 6.68(s,1H)；3.58-3.54(m,1H)；3.14-3.06(m,1H)；2.77(s,1H)； 2.46-2.36(m,1H)；2.03-1.98(m,2H)；1.81-1.62(m,1H)；1.56 -1.28(m,6H)。13C NMR(d-DMSO，100MHz)，:174.66，56.69，40.05， 38.63，35.46，34.70，28.92，25.40。ESI-MS：m/z:228.1[M+Na]+。
2. method of producing a composite material
2.1 animal model replication and grouping: one week after adaptive feeding of SD rats, diabetic rat models were constructed by tail vein injection of streptozotocin (dose 55mg/kg) in 0.01mol/L sterile citrate-sodium citrate buffer, pH 4.5. After 72h, measuring the fasting blood sugar of the rat, wherein the blood sugar is more than or equal to 16.7mmol/L, and the molding is successful if the urine sugar is positive. Rats were randomly divided into a diabetic group (DM group), a lipoic acid-treated group (ALA group), and a lipoamide-treated group (ALM group). 2 weeks after molding, lipoic acid and lipoamide are administered in a gastric lavage way, wherein the lipoic acid and the lipoamide are respectively suspended in 5 percent sodium carboxymethylcellulose (CMC-Na) aqueous solution, the gastric lavage dose is 150mg/kg/d, and the administration is carried out for 6 days per week; and a normal control group (NC group) with the same age of mice is arranged, and the CMC-Na aqueous solution with the same concentration and the same dosage is perfused. All rats were fed standard diet, ad libitum access, and blood glucose and body weight were monitored weekly. All rats were sacrificed after 6 weeks.
The experimental data are expressed by mean + -standard deviation (x + -s), SPSS17.0 software is applied, homogeneous variance test is adopted for group comparison, single-factor variance analysis is carried out, and statistical significance is shown when P is less than 0.05.
2.2 specimen collection: collecting urine for 24h by using a metabolism cage 1 day before the death of the rat, recording urine volume, taking part of urine, centrifuging, and storing at-20 ℃; fasting for 6-8h before sacrifice, weighing after ether anesthesia, collecting blood by femoral artery puncture, and separating serum and storing at-20 ℃; bilateral kidneys were harvested by laparotomy, the capsule and surrounding adipose tissue were removed, the weight to weight ratio (KW/BW) of the kidneys was recorded and fixed with 4% paraformaldehyde and stored at-80 deg.C, respectively.
Experimental example 1: comparative experiment of effects of lipoic acid and lipoamide on rat kidney weight/body weight ratio, serum Total Cholesterol (TC), Triglyceride (TG) and urine protein
Detecting serum Total Cholesterol (TC) and Triglyceride (TG) by enzyme analysis; the method for measuring Urine Protein (UP) by pyrogallol red colorimetry is operated according to the kit specification, and the product of urine Protein concentration and urine volume is 24h urine Protein volume (24 hUP).
TABLE 1 Change in Kidney weight/body weight ratio, 24h urine protein, Total Cholesterol, Triglycerides (x. + -.s) in groups of rats after 6 weeks of experiment
In comparison with the normal group,*P<0.05; compared with the group with the diabetes mellitus,#P<0.05; compared with the lipoic acid group, the composition has the advantages that,ΔP<0.05
as can be seen from Table 1, KW/BW, TC, TG and 24h UP of the lipoamide group (ALM) and the lipoic acid group (ALA) are all reduced (P is less than 0.05), and the reduction effect of the lipoamide on the TC and the TG is obviously stronger than that of the lipoic acid.
Experimental example 2: effect of lipoic acid or lipoamide on Total antioxidant Capacity (T-AOC), Catalase (CAT), superoxide dismutase (T-SOD), Malondialdehyde (MDA) in rats
All indices were determined colorimetrically with reference to kit instructions.
TABLE 2 comparison of oxidative stress levels (x. + -.s) in groups of rats after six weeks of experiment
In comparison with the normal group,*P<0.05; compared with the group with the diabetes mellitus,#P<0.05; compared with the lipoic acid group, the composition has the advantages that,ΔP<0.05
as shown in Table 2, the kidney T-AOC, T-SOD and CAT activities of rats in the diabetic group are reduced compared with those of the normal group (P <0.05), the lipoic acid and lipoamide can up-regulate the kidney T-AOC, T-SOD and CAT activities of rats in DM (P <0.05), and the lipoamide up-regulates the kidney T-AOC and T-SOD activities of the rats in diabetes (P <0.05) more obviously than the lipoic acid; compared with the normal rat, the kidney MDA content of the rat in the diabetic group is increased (P <0.05), the lipoic acid and the lipoamide can lower the kidney MDA content of the rat in the diabetic group, and particularly, the action of the lipoamide is more obvious (P <0.05), which shows that the lipoic acid and the lipoamide have the action of resisting oxidative stress, so that the occurrence and development of diabetic nephropathy are relieved or delayed, and the antioxidant action of the lipoamide is obviously stronger than that of the lipoic acid.
Experimental example 3: effect of lipoic acid (ALA) or lipoamide (ALM) on the morphological changes of rat Kidney tissue
The kidney tissue was fixed with paraformaldehyde, and 3 μm thick paraffin sections were prepared, stained with H & E and Masson, and the morphological changes of the kidney tissue were observed with a light microscope. H & E staining the methods for assessing tubulointerstitial damage were as follows: 10 20-fold microscopic fields were randomly selected in the renal cortex for systematic assessment (grade 1-6). Injury scoring criteria included tubular dilation, tubular atrophy, cast formation, range of interstitial mononuclear cells and extracellular matrix deposition as a percentage of total field (1 ═ 10%;, 2 ═ 10-25%; 3 ═ 26-50%, 4 ═ 51-75%, 5 ═ 76-95%, 6 ═ 95% and above).
H & E and Masson stain to see that the normal rat renal tubule structure is clear, the renal tubular epithelial cells are arranged neatly, the basement membrane is complete, and the interstitial tissue does not have inflammatory cell infiltration; the DM group rat has obvious renal tubule lumen expansion, irregular thickening of renal tubule basement membrane, vacuolated change of renal tubule epithelial cells, inflammatory cell infiltration of interstitial substance, and increase of Masson staining positive substances of the renal tubule interstitial substance; the kidney lesions of rats in ALA and ALM groups are improved to different degrees, Masson staining positive substances in tubulointerstitis are obviously reduced, and inflammatory cell infiltration is reduced. After H & E staining, the system injury rating ALM group is lower than that of ALA group, and the injury protection effect of lipoamide on kidney tissues is stronger than that of lipoic acid.
Experimental example 4: effect of lipoic acid (ALA) and lipoamide (ALM) on rat Collagen I
The distribution and expression of Collagen I in the kidney tissues of rats in each group are detected by an immunohistochemical staining method and an SP two-step method. Paraffin section is dewaxed and hydrated, and after being blocked by pancreatin repair antigen and 5% BSA, Collagen I (1: 100) is incubated at 4 ℃ overnight, biotinylated secondary antibody is added, the incubation is carried out for 30min at room temperature, SP reagent 3-amino-9-ethylcarbazole (AEC) is dripped for color development, hematoxylin counterstaining is carried out, PBS replaces primary antibody, and the negative control is used. Collagen I deposition was analyzed using a quantitative Image analysis system (Image-Pro + v 6.0): 10 visual fields containing glomeruli under a 40-fold mirror are randomly selected from the renal cortex for analysis, areas with positive staining are determined, arterial cavities are excluded from the study, and the proportion of the areas with positive staining to the total area is calculated.
The result shows that the Collagen I positive staining of the kidney tissue of a normal rat mainly exists in perivascular and intercellular spaces, while the positive staining of the kidney tissue of a diabetic rat is obviously increased, so that the strong positive staining of the renal tubular basement membrane can be seen. The expression of Collagen I is obviously reduced after the lipoic acid and the lipoamide are treated, particularly the expression of Collagen I is reduced more obviously after the lipoamide is treated than that of the lipoic acid group (P <0.05), which shows that the lipoic acid and the lipoamide can play an anti-diabetic kidney fibrosis effect by reducing the expression of Collagen I, and the lipoamide has stronger effect than that of the lipoic acid.
Experimental example 5: effect of lipoamide (ALM) on rat Kidney tissue transforming growth factor beta 1 expression, TAK1 protein expression and activation
Taking 200mg of kidney cortex of each group of rats stored at-80 ℃, respectively adding 200mg of tissue protein extracting solution into each sample, homogenizing and centrifuging to obtain supernatant, determining the protein concentration of each group by using a BCA kit (Biyun day), calculating the volume required by each lane according to the determined concentration, adding a sample adding buffer solution, boiling for 10min, carrying out electrophoresis separation by 8% SDS-PAGE gel, transferring onto a PVDF membrane, sealing for 1h at room temperature by 5% skimmed milk powder, respectively adding beta-actin, TGF-beta 1, TAK1 and p-TAK1 primary antibodies, and incubating for 12-24h at the working concentration of 1:4000, 1:300, 1:1000 and at the temperature of 4 ℃; on the next day, after washing the membrane with TBST, adding corresponding horseradish peroxidase-labeled secondary antibodies (the concentration is 1: 4000) to incubate for 1h at room temperature, adding ECL fluorescent developing solution, exposing by using a gel imager, analyzing each strip by imagelab software to adjust the volume value, repeating the operation for 3 times for each sample, taking a beta-actin protein strip as an internal reference, and expressing the result by using a target protein/beta-actin value.
The results showed that the normal control group (NC) expressed less TGF-. beta.1, less TAK1, and less P-TAK 1; the TGF-beta 1, the TAK1 and the P-TAK1 in the diabetes mellitus group (DM) are obviously increased compared with the normal group (P is less than 0.05); TGF-beta 1 and TAK1, P-TAK1 were all significantly reduced After Lipoamide (ALM) treatment compared to DM group (P < 0.05). The lipoamide can inhibit the expression of TGF-beta 1 and inhibit the expression and activation of TAK 1.
Experimental example 6: effect of lipoamide (ALM) on protein expression levels of the New protein N (SnoN) related to rat Ski
Detection of SnoN protein levels: taking 200mg of kidney cortex of each group of rats stored at-80 ℃, respectively adding 200mg of tissue protein extracting solution into each sample, homogenizing and centrifuging to obtain supernatant, determining the protein concentration of each group by using a BCA kit (Biyun day), calculating the volume required by each lane according to the determined concentration, adding a sample adding buffer solution, boiling for 10min, carrying out electrophoresis separation by 8% SDS-PAGE gel, transferring onto a PVDF membrane, sealing for 1h at room temperature by 5% skimmed milk powder, respectively adding beta-actin and SnoN primary antibodies, and incubating for 12-24h at 4 ℃ with the working concentrations of 1:4000, 1: 300; on the next day, after washing the membrane by TBST, adding corresponding horseradish peroxidase-labeled secondary antibodies (the concentration is 1: 4000) to incubate for 1h at room temperature, adding ECL fluorescent developing solution, exposing by a gel imager, analyzing each strip by image lab software to adjust the volume value, repeating the operation for 3 times for each sample, taking the beta-actin protein strip as an internal reference, and expressing the result by using the target protein/beta-actin value. In a normal control group, SnoN is highly expressed; the expression level of SnoN in the diabetic group (DM) was significantly reduced compared to the normal group (P < 0.05); the expression level of snoN in the sulfur octanoyl amide group is obviously up-regulated (P is less than 0.05) compared with the diabetes group. The lipoamide is shown to restore the expression of a key regulatory protein SnoN of the renal fibrosis.
Experimental example 7: effect of lipoamide (ALM) on the ubiquitination level of the novel protein N (SnoN) associated with rat Ski
Detection of SnoN ubiquitination level: 200mg of kidney cortex of each group of rats stored at-80 ℃ is taken, tissue protein extracting solution is respectively added into each sample, then the mixture is homogenized and centrifuged to take supernatant, and the protein concentration of each group is measured by using a BCA kit (Biyun day). Separating and purifying SnoN by Immunoprecipitation (IP), adding the extracted SnoN into a sample adding buffer solution, boiling for 10min, carrying out electrophoresis separation by 8% SDS-PAGE gel, transferring to a PVDF membrane, sealing for 1h by 5% skimmed milk powder at room temperature, adding ubiquitin, SnoN and IgG primary antibody respectively, and incubating for 12-24h at 4 ℃ with the working concentrations of 1:1000 and 1: 300; on the next day, after TBST membrane washing, adding corresponding horseradish peroxidase labeled secondary antibodies (the concentration is 1: 4000) to incubate for 1h at room temperature, adding ECL fluorescence developing solution, exposing by a gel imager, and comparing the blotting result to detect the ubiquitination level of the SnoN protein. In the normal control group (NC), ubiquinated SnoN protein was less expressed; compared with the normal group, the ubiquinated SnoN protein in the Diabetes Mellitus (DM) group is obviously increased; ubiquinated SnoN proteins in the lipoamide group (ALM) were significantly reduced compared to the diabetic group. The lipoamide can reduce the ubiquitination degradation of the SnoN protein and increase the stability of the SnoN protein.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in any way, and any simple modification, equivalent change and modification made to the above embodiment according to the technical spirit of the present invention are within the scope of the present invention without departing from the technical spirit of the present invention.
Claims (4)
1. Use of lipoamide for the preparation of a composition for delaying and treating diabetic renal fibrosis.
2. The use according to claim 1, wherein the composition reduces the expression of renal interstitial Collagen I (Collagen I) to exert the effects of resisting diabetes and renal fibrosis, thereby significantly improving renal fibrosis.
3. The use of claim 1, said composition promotes the expression level of the nuclear transcription co-suppressor, SnoN protein, critically regulated by renal fibrosis.
4. The use of claim 1, wherein the composition reduces ubiquitination level of a nuclear transcription co-suppressor (SnoN protein) critically regulated by renal fibrosis, and improves stability of the SnoN protein.
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