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Objective:To investigate the effect of Clostridium butyricum on renal tissue of db/db mice and to explore its mechanism. Methods:Fourteen-week-old db/db mice were divided into db/db group( n=10) and db/db+ Cb group( n=7) according to random number table method. Age-matched db/m mice were selected as the normal control group. The db/m and db/db mice were administered 0.9% sodium chloride solution by gavage, while the db/db+ Cb mice were administered an equivalent amount of Clostridium butyricum solution by gavage for 8 weeks. Serum creatinine , fasting blood glucose, urinary albumin to creatinine ratio(ACR) and other biochemical indicators were also detected. HE staining was used to observe the pathological changes of kidney tissue. The expressions of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) mRNA were detected by realtime PCR, while the expressions of nuclear factor-κB(NF-κB), glucagon-like peptide 1 receptor(GLP-1R), and adenosine monophosphate-activated protein kinase(AMPK) in kidney tissue were determined by immunohistochemistry and Western blotting. The levels of intestinal flora, serum and fecal short-chain fatty acids(SCFAs) were measured by 16S rRNA, liquid chromatograph-mass spectrometer, and gas chromatograohy-mass spectrometry respectively. Results:Compared to db/db mice, db/db+ Cb mice showed improvement in general condition after supplementation with Clostridium butyricum. Fasting blood glucose, blood urea nitrogen, albumin-to-creatinine ratio(ACR), blood creatinine, and levels of interleukin-6(IL-6) in kidney tissue were reduced(all P<0.05). The pathology showed various degrees of amelioration of kidney tissue injury in mice. The expression of PGC-1α mRNA increased in kidney tissue( P<0.05). Decreased expression of NF-κB protein, as well as increased expression of GLP-1R and phosphorylated(p-)AMPK/AMPK protein(all P<0.05) were detected in kidney tissues. Clostridium butyricum modulated the composition of the gut microbiota with elevated total SCFAs in blood and feces. Conclusion:Clostridium butyricum increased the expression of GLP-1R in kidney tissue, promoted AMPK phosphorylation, and alleviated renal tissue damage in mice. This suggests that it may be associated with regulating the abundance of SCFA-producing bacterial populations.
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Objective:To investigate the clinical diagnostic value of joint test of retinol-binding protein (RBP), cystatin C (CYSC) and urinary (albumin/creatinine ratio, ALB/Cr) ALB/Cr in early diabetes nephropathy.Methods:Data of 50 early diabetic nephropathy patients (EDN group) from Jan. 2020 to Jun. 2021 in our hospital, another 50 pure type 2 diabetic patients (T2DM group), and 50 healthy subjects (control group) were compared and analysed. RBP, CYSC and urinary ALB/Cr were tested for the 3 groups. Then the clinical diagnostic value between single index test and joint test for the early diabetes nephropathy were compared.Results:Group EDN had higher RBP, CYSC and urinary ALB/Cr [ (114.66±0.56) mg/L, (2.64±0.33) mg/L, (351.81±15.48) ] mg/g than group T2DM [ (83.58±0.83) mg/L, (1.41±0.29) mg/L, (113.65±12.55) mg/g] and control group[ (38.61±0.66) mg/L, (0.53±0.26) mg/L, (16.36±5.61) mg/g]. The difference was statistically significant ( P<0.05). The specificity and sensitivity of early diabetes nephropathy were 95.38% and 96.21%, both higher than single index test. Conclusion:The combined detection of serum RBP, CYSC and urine ALB/Cr has certain reference value for the clinical diagnosis of early diabetic nephropathy.
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Diabetes (DM) is one of the top five causes of death worldwide. Controlling glucose level is vital for protectingthe complications and improving the diabetics’ health. Olive (Olea europaea L.) leave extract (OLE) containsbiologically active antioxidant phenolic compounds. This research was carried out to evaluate the effect of OLEon oxidative status and advanced glycation end products (AGEs) in DM rats. Male Wister rats (n=40, 200 ± 20g) were divided into Group (1); Control rats and Groups (2-5); DM rats were intraperitoneal(i.p.) injected withSTZ (65 mg/kg), only DM rats (fasting blood glucose >250 mg/dl) were randomly classified into DM , DM+metformin (MT) (600 mg/kg) as reference drug, DM+OLE (200 mg/kg), and DM+OLE (400 mg/kg) groups. Atthe end of the experiment (6 weeks), blood and kidney samples were collected for biochemical andhistopathological studies. Serum glucose, renal functions (creatinine (Cr), and blood urea nitrogen (BUN)),electrolyte ions (sodium (Na+) and potassium (K+)), as well as renal oxidative statusbiomarkers (nitric oxide(NO), malondialdehyde (MDA), superoxide dismutase (SOD), and AGEs) were determined. The results revealedthat there were significant increases in glucose, Cr, BUN, and K+ with a significant decrease in Na+ levels, aswell as significant decrease in renal oxidative stress and elevated AGEs levels compared to the control rats.Although MT treatment was more effective than OLE (400 mg/kg) in reducing glucose level, while OLEtreatment was more effective than MT in reducing oxidative stress and AGEs levels. Oral administration of OLE(400 mg/kg) showed significant hypoglycemic and antioxidant effects as well as improved renal functions andinhibited AGEs levels compared to the DM rats. Also overcome most of the renal histopathological changesinduced by DM. Therefore, co-administration of MT and OLE is recommended in preventing DM complications
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@#Introduction: Diabetic nephropathy is one of the most common complications in diabetes Mellitus. Hyperglycemia and chronic inflammation cause abnormal oxidative stress deposition that leads to the decrease of glutathione peroxidase-1 (GPx1) and endothelial Nitric Oxide synthetase (eNOS). It was reported that Centella asiatica has an anti-hyperglycemic and anti-inflammatory effect. However little is known about Centella asiatica effect in the kidney of DM. The objective of this study was to know the effect of Centella asiatica extract on Kim-1 (marker of kidney damage), GPx1 and eNOS mRNA expression in the kidney of DM rat model. Methods: Wistar DM rat model was divided into 6 groups namely non-DM group, DM group , DM with captopril and another DM group treated with Centella asiatica with three different dosages (250, 500 and 1000 mg/kg BW). The treatment was given for 8 weeks. The Kim-1, GPx1 and eNOS expression was measured using semi-quantitative PCR. Results: The DM group showed higher Kim-1 kidney mRNA expression but lower GPx1 and eNOS kidney mRNA compare to those on the non-DM group. Administration of Centella asiatica improves the expression of Kim-1, GPx1 and eNOS kidney mRNA expression in DM rat model. Conclusion: Centella asiatica has the potential to prevent kidney damage in DM rat model by improving Kim-1, GPx1 and eNOS kidney mRNA expression.
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@#Introduction: Association studies between single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) have been abundant. However, there are limited reports on copy number variations (CNVs) of beta-defensins (DEFB) gene in relation to T2DM. In this study, DEFB copy numbers were quantified in T2DM with nephropathy, T2DM without nephropathy and non-diabetic control groups to investigate its influence in chronic inflammation in Malaysian individuals. Methods: DEFB copy number in Malaysian individuals were quantified by using paralogue ratio tests (PRT) which allow direct quantification of gene copy number by using PRT107A and HSPD21 PRT primers. The copy number generated was then validated from insertion/deletion ratio measurement 5DEL (rs5889219) and two microsatellite analyses (EPEV-1 and EPEV-3). Results: DEFB copy number was found extending from 2 to 8 copies in the non-diabetic group (n=146), while in T2DM group (n=392), copy numbers were more extensive, ranging between 1 and 12 copies; with 1, 10 and 12 copies detected in T2DM with nephropathy group (n=202). Statistically, there is no significant difference in DEFB copy number between T2DM and the non-diabetic group (p=0.209) as well as between diabetic nephropathy and without nephropathy of the T2DM group (p=0.522). However, significant white blood cell (WBC) count was found between T2DM groups with and without diabetic nephropathy (p=0.000). Conclusion: Extreme DEFB copy numbers in T2DM with nephropathy group suggest future studies with bigger sample size are necessary to elucidate the true impact of CNVs of DEFB gene in promoting early onset of nephropathy in T2DM.
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Aim To investigate the protective effect of bezafibrate on renal injury and the changcs of 20- HETE in mice with diabetic nephropathy. Methods A diabctic model was established by long-term high-energy feeding combined with streptozotocin. The structural and functional changes of kidney were evaluated by renal pathological examination and blood urea nitrogen (BUN), serum creatinine ( Scr) , urinary albumin levels. The expressions of PPAIls and CYP4A protein were detected by Western blot. The level of 20-HETE was measured by ELISA kit. Results After four weeks with high-energy feeding, streptozotocin (40 mg • kg-1 • d"1 i. p) administration had been performed for five days. Then after seven days,fasting blood glucose (FBG) of mice exceeded 11.1 nimol • L"1, which suggested the establishment of the diabetic model. After four weeks of diabetic onset, the levels of BUN,Scr,urinary albumin increased significantly (P er and thickened basement membrane were observed in diabetic mice. Meanwhile,the expressions of PPARs and CYP4A protein in the kidney and the content of 20-HETE in serum decreased in model group (P <0. 01). With bezafibrate supplementation (75 mg • kg"' • d"1) for four weeks, both the structure and function of kidney were improved in diabetic mice,with the up-regulation of PPARs and CYP4A protein expressions and the increase of 20-HETE level (P <0. 01 ). Conclusions Bezafibrate can ameliorate renal injury in diabetic mice, which may be related to activating CYP4A-20-HETE.
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Objective To research the correlation of single nucleotide polymorphisms(SNPs) of Plasmacytomas Variant Translocation Gene(PVT1) and diabetes nephropathy.Methods To assay PVT1 SNPs (rs10808565,rs13447075,rs2648862,rs2720709,rs2648875) in two groups individuals with diabetes nephropathy and diabetes by MassARRAY system.Then analysis the results by statistical methods to evaluate the relationship between PVT1 SNPs and diabetes nephropathy.Results The distributions of SNPs of PVT1 (rs10808565,rs13447075,rs2648862,rs2720709,rs2648875) were all under the Hard-Weinberg equilibrium in two groups.Difference in PVT1 rs2648875 between two groups was statistically significant(P<0.05);and there were no significant differences in the others SNPs (rs10808565,rs13447075,rs2648862,rs2720709) between two groups.Conclusion PVT1 rs2648875 may contribute to the susceptibility of DN in chinese people and the others PVT1 SNPs (rs10808565,rs13447075,rs2648862,rs2720709) may not be Chinese susceptibility gene in DN.
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Objective:To investigate the relationship of micro-inflammation,cellular and humoral immune function and kidney disease of patients with diabetic nephropathy. Methods:124 cases of DN were randomly divided into normal albuminuria group ( NA, n=35),microalbuminuria group (MA,n=45) and clinical albuminuria groups(CP,n=44) based on 24 h urinary albumin excretion rate ( UAER) and the healthy subjects were selected as the control group ( n=35 ) . The levels of C-reactive protein ( CRP ) were measured with radioimmunoassay,the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α) and humoral immunity(IgG enzyme-linked immunosorbent assay,IgA,IgM) were measured with ELISA. The levels of immune response ( CD4+Th17,Th17/Treg, CD4+ CD25+ Treg) were measured with flow cytometry cellular. The levels of creatinine ( Scr) ,cystatin C ( CYSC) and UAER of each groups were analyzed with fully automated biochemistry. Results:The levels of CRP,IL-6,TNF-α,Scr,CYSC,UAER of NA group,MA group,CP groups were higher than control groups(P<0. 05),the levels of CRP,IL-6,TNF-α,Scr,CYSC,UAER of CP groups were higher than NA,MA group (P<0. 05). The levels of CD4+CD25+ Treg,IgG were lower than the control group (P<0. 05),while the levels of CD4+ CD25+ Treg,IgG of CP groups were higher than NA group,MA group (P<0. 05). The levels of IgA,IgM,Th17/Treg, CD4+ Th17 of NA group,MA group,CP groups were higher than control groups(P<0. 05). The levels of CRP,IL-6,TNF-α were positively correlated with Scr, CYSC, UAER ( P<0. 05 ) and were negatively correlated with Th17/Treg, CD4+CD25+ Treg, IgG ( P<0. 05). Conclusion:DN patients with micro inflammatory status and immune function disorder,through the control or elimination of pro-inflammatory factors,improve the immune function of DN patients to delay the occurrence and progress of DN patients has important significance.
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Objective To explore the neutral grain cell gelatinase associated lipid lipocalin(NGAL ) and β2 microglobulin (β2‐MG) predictive value of diabetic nephropathy(DN) .Methods From January 2015 to April 2016 in the hospital for 78 cases of DN patients recorded as the observation group ,and then 50 cases of healthy volunteers were choosen as the control group at the same period .NGAL ,β2‐MG ,BUN ,SCr and GFR levels were compared in the two groups .And the positive rate and correlation were ana‐lyzed .Results The levels of NGAL and β2‐MG in the observation group were(473 .21 ± 127 .09)ng/mL ,(2 .76 ± 0 .45)mg/L , which were significantly higher than that in the control group(61 .36 ± 14 .230)ng/mL ,(0 .81 ± 0 .14)mg / ,respectively .The posi‐tive rate of NGAL and β2‐MG in the observation group were 96 .15% (75/78) ,91 .03% (71/78) ,which were significantly higher than that of the control group of 2% (1/50) ,6% (3/50) .While the BUN ,SCr in observation groups were significantly higher than that in the control group ,while the level of eGFR was significantly lower than that of the control group ,the differences were statis‐tically significant(both P< 0 .05) .NGAL ,β2‐MG and BUN ,SCr showed positive correlation(R = 0 .812 ,P= 0 .000 ;R = 0 .728 ,P=0 .001 ;R = 0 .748 ,P= 0 .001 ;R = 0 .685 ,P = 0 .021 ) ,and eGFR showed a negative correlation (R = - 0 .415 ,P = 0 .000 ;R=- 0 .371 ,P= 0 .000) .Conclusion The level of NGAL and β2‐MG in DN patients is significantly increased ,NGAL ,β2‐MG levels are significantly correlated with BUN .
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Objective To investigate the risk factors of albuminuria in type 2 diabetes nephropathy patients. Methods 870 hospitalized patients with type 2 diabetes mellitus were included in the study. The patients were divided into normal buminuria group (n = 634) and persistent albuminuria group (n = 236) according to the 24h urinary albumin excretion. Diabetic chronic complication and related biochemical indicators were analyzed. Independent risk factors associated with diabetic nephropathy were analyzed. Results The differences in duration of diabetes, age, SBP, DBP, Hb, HbA1C, UA, TG, CHOL-C, HDL-C, diabetic retinopathy (DR), cardiovascular and cerebrovascular disease were statistically significant between two groups (P < 0.01). Regression analysis showed that independent risk factors of albuminuria of DN included duration of diabetes, SBP, Hb, UA, TG and DR. Conclusions Such risk factors of duration of diabetes, SBP, UA, TG, Hb and DR may be associated with the occurrence and severity of albuminuria of DN.
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Objective The separation of various proteins in urine was used to differentiate the types of urinary protein to determine the site of diabetic kidney damage and lesions. Methods We used sodium dodeeyl sulfonate - agarosegel electrophoresis(SDS - AGE) to detect the unconccntrated urine on 108 cases patients with diabetic nephropathy urine specimens analysis. Results The results of urinary protein electrophoretic of 108 patients displayed: 4 eases for renal tubular proteinuria, 10 eases for physiological proteinuria, 22 eases for glomerular proteinuria, 72 cases for mixed proteinuria. Conclusion Urine protein electrophoresis for diabetic nephropathy patients with positive can distinguish the various components, and to understand the degree of kidney damage and lesions. This method is low -cost, non - invasive and highly sensitive. The film can be stored. It is worthy to be popularized.
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Objective The separation of various proteins in urine was used to differentiate the types of urinary protein to determine the site of diabetic kidney damage and lesions.Methods We used sodium dodecyl sulfonate-agarosegel electrophoresis(SDS-AGE) to detect the unconcentrated urine on 108 cases patients with diabetic nephropathy urine specimens analysis.Results The results of urinary protein electrophoretic of 108 patients displayed: 4 cases for renal tubular proteinuria,10 cases for physiological proteinuria,22 cases for glomerular proteinuria,72 cases for mixed proteinuria.Conclusion Urine protein electrophoresis for diabetic nephropathy patients with positive can distinguish the various components,and to understand the degree of kidney damage and lesions.This method is low-cost,non-invasive and highly sensitive.The film can be stored.It is worthy to be popularized.