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Aim To investigate the mechanism of corn silk decoction on diabetic nephropathy (DN) rats using metabolomics technology. Methods DN rat model was established by feeding with high-sugar and high-fat diet, combined with intraperitoneal injection of low dose streptozotocin. Renal organ index, fasting blood glucose, albumin creatinine ratio, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol indexes were measured, and the pathological changes of renal tissues were also observed to evaluate the intervention effect of corn silk on DN model rats. Further, UPLC/Q-TOF-MS technology was used to screen potential biomarkers in renal tissues and urine, combined with principal component analysis (PC A) and orthogonal partial least squares discriminant analysis (OPLS-DA). After identification by HM-DB and KEGG database, the biomarkers were imported into MetaboAnalyst for metabolic pathway analysis. Results All indexes and pathological damage of kidneys were improved in groups with different doses of corn silk, indicating that corn silk had a good intervention effect on DN. Metabolomic analysis showed that 18 biomarkers could be significantly called back by corn silk, and it involved 18 metabolic pathways mainly including phenylalanine, tyrosine and tryptophan biosynthesis, riboflavin metabolism, arachidonic acid metabolism, and tyrosine metabolism. Conclusions The mechanism of corn silk decoction intervention on DN may be related to amino acid metabolism, riboflavin metabolism, and arachidonic acid metabolism.
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OBJECTIVE：To study the effects of Modified liuwei dihuang decoction on kidney/bone injury of chronic kidney disease-mineral and bone disorder（CKD-MBD）model rats. METHODS ：The male SD rats were randomly divided into normal group（n＝10），high phosphorus group （n＝30），model group （n＝30），calcitriol group （positive control ，0.09 μg/kg，n＝30）， Modified liuwei dihuang decoction group （10 g/kg by crude drug ，n＝30）. CKD-MBD model was established by high phosphorus and adenine diet for 6 weeks. After modeling ，normal group and model group were given normal diet/high phosphorus diet and intragastric administration of water. Administration groups were fed with normal diet and given corresponding solution intragastrically（water as solvent ），0.1 mL/kg，once a day ，for consecutive 6 weeks. Blood sample of rats in the normal group were collected ，and they were sacrificed after the last administration. Blood sample of 10 rats in each other group were collected ， and they were sacrificed at 2，4 and 6 weeks after administration. The contents of blood urea nitrogen （BUN），serum creatinine （Scr），calcium，phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum were detected in each group. The bone mineral density（BMD）of femoral was measured ，the morphological changes of renal tissue and bone tissue were observed ，and the percentage of renal tubular injury and the score of renal interstitial fibrosis were calculated. RESULTS ：Compared with normal group，above indexes in high phosphorus group had no significant change at different time points （P＞0.05）. There was no abnormal change in renal/bone tissue. Compared with high phosphorus group at the same time point ，the contents of BUN ，Scr， phosphorus，iPTH，FGF-23，RANKL and osteocalcin in serum ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in the model group were significantly increased ，while the contents of calcium in serum and the BMD of femoral were significantly decreased （P＜0.05 or P＜0.01）. The renal tissue showed diffuse fibrosis. The width of trabecular bone was increased and the number of osteoblasts was decreased. Compared with the model group at the same time point ，the contents of BUN（except for Modified liuwei dihuang decoction group after 2 weeks of administration ），Scr，serum phosphorus ，iPTH， FGF-23，RANKL and osteocalcin ，the percentage of renal tubular injury and the score of renal interstitial fibrosis in Modified liuwei dihuang decoction group and calcitriol group were decreased significantly at each time point ；serum calcium content and BMD（except for 2 weeks of administration ）were significantly increased （P＜0.05 or P＜0.01），and the pathological changes of renal/bone tissue were significantly improved ；there was no statistical significance in above indexes between Modified liuwei dihuang decoction group and calcitriol group （P＞0.05）. CONCLUSIONS ：Modified liuwei dihuang decoction can improve kidney/ bone injury of CKD-MBD model rats ，and improve BMD and regulate disorder of calcium and phosphorus metabolism.
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Post chemotherapy Wilms Tumour (PCWT) is a diagnostic conundrum both for the clinician and the pathologist, in view of its morphological similarity with ectopic immature renal tissue (EIRT). However, due to their varying prognoses and different lines of management, it is important to distinguish between the two. Here, we discuss clinical presentation and pathology of a case of PCWT, arising in a horse shoe deformity of the kidney in a 5 year old girl. The discussion focuses on the pathogenesis of Extra Renal Wilms Tumour (ERWT) as well as its distinguishing morphological features and chemotherapy induced changes in Wilms tumour.
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Objective To study the mechanism of Comus officinalis glucosides treatment of IgA nephropathy.Methods Fifty SD rats were randomly divided into the control group,the IgAN model group,the Dexamethasone group,the Comus officinalis glucosides in the high-dose group and in the low-dose group.The IgA nephropathy rat models were established by feeding bovine serum albumin (BSA),subcutaneous injection of carbon tetrachloride (CCl4),castor oil and injecting tail vein with lipopolysaccharide (LPS).After 10 weeks of administration,the urine red blood cell count,UTP in each phase were observed after the rat models were successfully established.Then Dexamethasone group and Comus officinalis total glucoside group were given medicine for 8 weeks,and urine or serum content of interleukin-18 (IL-18),transforming growth factor-β1 (TGF-β1) in different groups of rats and pathological changes of kidneys were detected.Results Compared with the IgAN model group,24 h-UTP of each group decreased and Comus officinalis glucosides in high-dose group decreased extraordinary [(8.8 ± 3.2) mg/24 h vs.(35.2 ± 5.6) mg/24 h,t =10.511,P =0.000].Compared with the IgAN model group,urine red blood cell count decreased significantly in the high-dose group of Comus officinalis glucosides[(148.2 ±41.8) 个/μL vs.(683.8 ±24.6) 个/μL,t =10.909,P =0.000];but urine red blood cell count in the Dexamethasone group declined slightly,but there was no statistically significant difference(t =3.014,P =0.061).Compared with the control group,IL-18,TGF-β1,and rat urine or serum of IgAN model group was significantly elevated (all P ＜ 0.05).Compared with IgAN model group,IL-18,TGF-β1 of the high-dose group of Comus officinalis glucosides in rats urine or serum decreased significantly(all P ＜ 0.05).The effect of high-dose group of Comus officinalis glucosides on the pathological changes in kidney tissues was the most significant.Conclusions The mechanism of Comus officinalis glucosides may postpone renal lesion that can be associated with the down-regulation of the expression of IL-18,TGF-β1 and the inhibition of the deposition of IgA in the renal tissue.Comus officinalis glucosides can inhibit the proliferation of mesangial cells,tubular atrophy and interstitial fibrosis in IgAN rats,which has a certain curative effect on IgAN rats.
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Objective To analyze and identify the protein of patients with IgA nephropathy for identification and quantitative a-nalysis using the combination of liquid chromatography and mass spectrometry which combined isobaric tags for relative and abso-lute quantification .Methods Proteomic analysis of renal tissue in patients with IgA nephropathy and normal controls was per-formed to identify different expressed proteins .Results A total of 1860 proteins were identified ,287 proteins were upregulated in renal tissue of IgA nephropathy patients ,287 proteins were downregulated significantly ,finally 9 upregulated proteins and 8 down regulated proteins were identified(protein fold difference greater than 1 .5) .Conclusion Quantitative proteomic technology is effi-ciently applicable for identification and relative quantitation of proteome in renal tissue ,which could get all the information of differ-ent protein .This is useful for us to better understand the relationship of protein and the pathogenesis of IGA nephropathy .
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Objective To investigate the expressions and clinical significance of Toll like receptor (TLR) 3 and TLR4 in peripheral blood mononuclear cells and renal tissues of children with primary IgA nephropathy.Methods A total of 34 children with primary IgA nephropathy were selected as the IgA nephropathy group,who were confirmed by renal biopsy,from the Department of Pediatrics,the First Affiliated Hospital of Xinxiang Medical University,from September 2014 to June 2016.In the same period,7 cases of renal tumor who underwent nephrectomy in Pediatric Surgery became control group A,and 10 cases of healthy children became control group B,and the expressions of TLR3 and TLR4 in renal tissue were detected by adopting immunohistochemistry between IgA nephropathy group and control group A,and the positive expression rate of TLR3 and TLR4 in peripheral blood mononuclear cells were detected by using flow cytometry in IgA nephropathy group.The expression of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group and control group B were observed and compared.Results The expressions of TLR3 and TLR4 in renal tissue of IgA nephropathy group were respectively (68.28 ±6.37)％ and 0.048 ±0.018,which were significantly higher than TLR3 [(9.69 ±11.02)％] and TLR4 (0.003 ±0.001) in the control group A,and the differences were statistically significant (t =50.080,14.374,all P ＜ 0.01).The positive expressions of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group were respectively (17.62 ± 8.33)％ and (23.85 ± 11.82)％,while the expressions were (0.31 ± 0.06) ％ and (3.02 ± 0.09) ％ respectively in the control group B,and the differences were statistically significant (t =12.109,11.612,all P ＜ 0.05).Conclusion The expressions of TLR3 and TLR4 in renal tissue and peripheral blood mononuclear cells of IgA nephropathy are increased,suggesting that the abnormal activation of TLR3 and TLR4 may be involved in the pathogenesis of IgA nephropathy.
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Objective To analyze and identify the protein of patients with IgA nephropathy for identification and quantitative a-nalysis using the combination of liquid chromatography and mass spectrometry which combined isobaric tags for relative and abso-lute quantification .Methods Proteomic analysis of renal tissue in patients with IgA nephropathy and normal controls was per-formed to identify different expressed proteins .Results A total of 1860 proteins were identified ,287 proteins were upregulated in renal tissue of IgA nephropathy patients ,287 proteins were downregulated significantly ,finally 9 upregulated proteins and 8 down regulated proteins were identified(protein fold difference greater than 1 .5) .Conclusion Quantitative proteomic technology is effi-ciently applicable for identification and relative quantitation of proteome in renal tissue ,which could get all the information of differ-ent protein .This is useful for us to better understand the relationship of protein and the pathogenesis of IGA nephropathy .
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To screen the differentially-expressed microRNAs (miRNAs) in mouse models with renal ischemia-reperfusion injury (IRI),aiming to offer foundation for unraveling the molecular mechanism of the incidence and progression of IRI.Methods The mouse models with acute IRI were established by renal artery clamping.Fifteen mice were divided into the IRI group and sham surgery group (E group).The animals in the IRI group were subdivided into the A group (45 min ischemia followed by 24 h reperfusion),B group (25 min ischemia followed by 24 h reperfusion),C group (45 min ischemia followed by 4 h reperfusion) and D group (25 min ischemia followed by 4 h reperfusion) (n=3 for each group).The severity ofIRI was evaluated by histological changes and renal function.The differentially-expressed miRNAs in the IRI mouse models at different ischemia time (25 and 45 min) and reperfusion time (4 and 24 h) were screened by using cluster analysis of miRNAs microarray data.The differential expression of miR-695 and miR-145 was validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).Results Both histological changes and renal function confirmed that the IRI mouse models were successfully established.Compared with the sham surgery group,71 differentially-expressed miRNAs were detected in the IRI group including 30 down-regulated miRNAs and 40 up-regulated miRNAs.The results of qRT-PCR demonstrated that if the standardized expression level of miRNAs in the E group was 1,the relative expression levels of miR-695 and miR-145 were 11.82 and 0.31 in the IRI group (both P＜0.05),which were consistent with the chip results.Conclusions After renal IRI,different changes occur in the gene expression profile of miRNAs.These differentially-expressed miRNAs act as molecular biomarkers for renal IRI with potential clinical and scientific research values.
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Objective To investigate the expressions and clinical significance of Toll like receptor (TLR) 3 and TLR4 in peripheral blood mononuclear cells and renal tissues of children with primary IgA nephropathy.Methods A total of 34 children with primary IgA nephropathy were selected as the IgA nephropathy group,who were confirmed by renal biopsy,from the Department of Pediatrics,the First Affiliated Hospital of Xinxiang Medical University,from September 2014 to June 2016.In the same period,7 cases of renal tumor who underwent nephrectomy in Pediatric Surgery became control group A,and 10 cases of healthy children became control group B,and the expressions of TLR3 and TLR4 in renal tissue were detected by adopting immunohistochemistry between IgA nephropathy group and control group A,and the positive expression rate of TLR3 and TLR4 in peripheral blood mononuclear cells were detected by using flow cytometry in IgA nephropathy group.The expression of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group and control group B were observed and compared.Results The expressions of TLR3 and TLR4 in renal tissue of IgA nephropathy group were respectively (68.28 ±6.37)％ and 0.048 ±0.018,which were significantly higher than TLR3 [(9.69 ±11.02)％] and TLR4 (0.003 ±0.001) in the control group A,and the differences were statistically significant (t =50.080,14.374,all P ＜ 0.01).The positive expressions of TLR3 and TLR4 in peripheral blood mononuclear cells of IgA nephropathy group were respectively (17.62 ± 8.33)％ and (23.85 ± 11.82)％,while the expressions were (0.31 ± 0.06) ％ and (3.02 ± 0.09) ％ respectively in the control group B,and the differences were statistically significant (t =12.109,11.612,all P ＜ 0.05).Conclusion The expressions of TLR3 and TLR4 in renal tissue and peripheral blood mononuclear cells of IgA nephropathy are increased,suggesting that the abnormal activation of TLR3 and TLR4 may be involved in the pathogenesis of IgA nephropathy.
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OBJECTIVE:To observe the effect of pathological lesion of renal tissue in rats with spontaneous hypertension (SHR),and study its mechanisms based on nuclear factorκB(NF-κB)signaling pathway. METHODS:21 SHR were randomly di-vided into model group and ICA low-dose,high-dose groups(20,40 mg/kg,denoted by ICA-L,ICA-H groups);other 7 homolo-gous Kyoto rats (WKY) were regarded as control group. All rats were intragastrically administrated,twice a day,for 11 weeks, rats in control group and model group received equal volume of double distilled water,ig. Pathological changes in renal tissue in each group were observed;Western blot method was used to detect protein expressions of p-NF-κB-p65,IκB and TNF-α in renal tissue. RESULTS:Compared with control group,model group showed disorder renal structure,narrow and irregular glomerular cysts;the protein expression of IκB was significantly down-regulated,protein expressions of p-NF-κB-p65 and TNF-α were signifi-cantly up-regulated(P0.05). CONCLUSIONS:ICA plays a role in improving renal pathological lesion in SHR,and the mechanism may be related to inhibiting NF-κB signaling pathway.
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Objective To explore the condition of cortistatin (CST)expression in human renal tissue and the changes in the level of CST in IgA nephropathy (IgAN)of different degrees.Methods Ten tumor adjacent normal renal tissue samples were collected.The mRNA and protein expressions of CST in human renal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR)and Western blotting,respectively.Immunohistochemisty (IHC)was performed to locate the expression of CST in renal tissue.According to the grading system of Lee et al,IgAN was divided into three groups:grade Ⅰ -Ⅱ (group A),grade Ⅲ -Ⅳ (group B),and grade Ⅴ (group C),and ten renal biopsy tissue samples were collected for each group.IHC was performed to detect the change in the level of CST in normal and IgAN renal tissue of different degrees.The effect of clinical indices on the level of CST in IgAN renal tissue was assessed by multiple linear regression analysis.Results RT-PCR and Western blotting showed that CST was expressed in renal tissue and IHC showed that CST was expressed on renal tubular epithelial cells.In IgAN,the higher the pathological grade was, the higher the expression of CST in renal tubules was.Multiple linear regression analysis showed that the pathological grade was associated with the expression of CST in renal tissue (r =0.875,P <0.01).Conclusion CST may participate in the inflammatory reaction of IgAN pathological injury and exert anti-inflammation effects.
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OBJECTIVE: To establish the method of high-performance liquid chromatography (HPLC) for the determination of polymyxin B content in renal tissue of rats and compare the results with that by LC-MS/MS. METHODS: The homogenate of kidney was deproteinized with sulfosalicylic acid. The separation was performed on a Platisil ODS C18 column, and the mobile phase was composed of acetonitrile-sodium sulphate (7 g · L-1)-phosphoric acid (6.8%, V/V) -water(22.25: 50: 5: 22.75) at a flow rate of 1.0 mL · min-1. The detection was conducted by UV at 205 nm. The rats in all the groups were given polymyxin B 2.5 mg · kg-1 · d-1 for 2 d through tail vein, then given polymyxin B 4, 8 and 16 mg · kg-1 · d-1 for 3 d. The concentration of polymyxin B in kidneys was determined by HPLC and LC-MS/MS, respectively. RESULTS: The linear range of the HPLC assay was 2-20 μg · mL-1 (r = 0.997 8). The average absolute recovery was 97% - 102% for the high, middle, and low concentrations. The relative standard deviations obtained for the inter- and intra-day assay were both less than 5%. The concentrations of polymyxin B in the different dose groups were (86.16 ± 3.28), (47.40 ± 0.51) and (21.48 ± 1.63) μg · g-1, respectively. The results obtained by LC-MS/MS were (80.64 ±2.17), (42.44 ±0.61), and (24.46 ±3.04) μg · g-1, respectively. The difference of the results of the two methods was within 20%. CONCLUSION: The established HPLC method can be applied to determine polymyxin B content in kidney, the results of which are similar to those determined by LC-MS/MS.
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The present experiment was planned to study nephrotoxicity in experimental diabetic rats under sub-chronic exposure to arsenic. Alloxan induced diabetic and control rats were exposed to sodium arsenite (0 and 5.5 mg/kg, orally) for 30 days. More pronounced nephrotoxic effects were noted in arsenic exposed diabetic group as evidenced by increased blood urea nitrogen, serum creatinine and relative kidney weight and decreased level of reduced glutathione and glutathione peroxidase activity compared to non arsenic exposed diabetic group. Increased level of lipid peroxidation, protein oxidation, superoxide dismutase and catalase activities under diabetic condition remained unchanged in arsenic exposed diabetic group compared to unexposed diabetic group.
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OBJECTIVE:To study the mechanism of renal toxicity of platinums in rats.METHODS:A total of 12 rats were equally assigned to receive cisplatin,carboplatin,or dicycloplatin i.v with the dosage of platinum at 10 mg?kg-1.The cumulative excretion rate of platinum in urine in 4 h and the concentration of platinum in renal tissue were measured by atom absorption method.RESULTS:The total excretion percent of platinum in urine in the first 4 h after injection of cisplatin,carboplatin,and dicycloplatin were(33.7?5.7)%,(89.1?8.5)% and(70.1?9.8)% respectively.The renal platinum concentration were 70.6?31.6,217.7?97.6,and(278.8?112.0)?g?g-1,respectively.CONCLUSIONS:Both the renal excretion speed and renal concentrations of platinum were higher for dicycloplatin and carboplatin than for cisplatin.The nephrotoxicity of platinum drugs probably has no direct relationship with the renal concentration of platinum.
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Objective To explore changes of local renin-angiotensin system(RAS)in renal tissue of rat during short-and mid-term tail suspension,as well as their relations with humoral regulation and renal function induced by real or simulated weightlessness.Methods 1-and 4-week(wk)tail-suspended rat model were used to simulate short-and mid-term weightlessness,respectively.Reverse transcriptase polymerase chain reaction(RT-PCR)was carried out to examine the mRNA expression of components of local RAS in renal tissue.Results Except for angiotensin Ⅱ receptor type 2(AT2),all of the other components of local RAS,including angiotensinogen(AGT),renin,angiotensin converting enzyme(ACE),angiotensin Ⅱ receptor type 1a(AT1a)and angiotensin Ⅱ receptor type 1b(AT1b),were found their expression in renal tissue of Sprague-Dawley rats.After 1 wk of tail suspension,mRNA expression of renin in renal tissue increased significantly(P
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BACKGROUND: Agonists of the peroxisome proliferator-activated receptor gamma may help to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to determine the anti- inflammatory effects of rosiglitazone on renal injury in sepsis model. METHODS: In lipopolysaccharide (LPS)-induced mouse sepsis, we examined the effect of rosiglitazone on LPS-induced overproduction of inflammatory mediators, on the expression of adhesion molecules, on the infiltration of inflammatory cells and on renal function. RESULTS: Rosiglitazone significantly decreased serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels during sepsis. The levels of blood urea nitrogen and creatinine were significantly lower in mice pretreated with rosiglitazone than that in LPS-treated mice. Rosiglitazone reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in renal tissue of LPS-treated mice. Pretreatment with rosiglitazone reduced the infiltration of macrophages/ monocytes in renal tissue. CONCLUSION: These results indicate that pretreatment with rosiglitazone attenuated the production of TNF-alpha and IL-1beta and reduced adhesion molecule expression and infiltration of inflammatory cells in renal tissue of LPS-treated mice. Therefore, rosiglitazone may have a protective effect in maintaining renal function and reducing mortality and morbidity in sepsis.
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Animals , Mice , Blood Urea Nitrogen , Creatinine , Inflammation , Intercellular Adhesion Molecule-1 , Interleukins , Monocytes , Mortality , PPAR gamma , Sepsis , Tumor Necrosis Factor-alpha , Vascular Cell Adhesion Molecule-1ABSTRACT
Hepatitis B virus(HBV) infection has been suggested as the etiologic agent in membranoproliferative glomerulonephritis(MPGN), but the mechanism by which HBV infection leads to MPGN in human has not been established. To localize the HBV antigen and HBV-DNA in the kidney tissue, we examined paraffin sections of kidney biopsies which were positive for HBsAg by immunohistochemical study from 13 HBV carriers with MPGN (HBV-MPGN). Polymerase chain reaction(PCR) and in situ PCR(ISP) were used for the HBV DNA amplification and localization in kidney tissues. Primers used in PCR and ISP were from the S, C, and X HBV-DNA regions. Immunohistochemical study showed HBsAg deposits on the mesangium and glomerular capillaries. Arteriolar deposits were also occasionally observed. PCR for the S, C, and X regions were positive in 11 patients(85%), 11 patients(85%), and 9 patients (69%), respectively. The PCR findings were further confirmed by direct sequencing of PCR products and the amplification of HSP70 gene as a control. ISP showed the amplified HBV-DNA at the glomeruli and renal tubules. For S region, ISP was positive in 7 patients. For C and X regions, ISP was positive in 8 patients, respectively. 5 patients showed the positive signals for both the glomeruli and tubules, while 4 patients were positive at the tubules only. These 4 patients seemed to have the longer disease durations when compared to the other 5 patients (52.8 months vs. 11.8 months), but it was not statistically significant. In conclusion, the detection and the localization of HBV antigen and DNA in renal tissues indicate the presence of the complete virion in the kidney. These results suggest that HBV may infect the kidneys of HBV carriers with MPGN.
Subject(s)
Humans , Biopsy , Capillaries , DNA , Glomerulonephritis, Membranoproliferative , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , Hepatitis , Immunohistochemistry , Kidney , Paraffin , Polymerase Chain Reaction , VirionABSTRACT
Objective To probe the changes of RAGEmRNA expression in renal tissue of.streptozotocin (STZ)-induced diabetic rats. Methods Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used in control rats and diabetic rats for 12 weeks. Results After 4 weeks of diabetes inducement, RACEmRNA level showed a continuous increase both in diabetic renal cortex and medulla. However, this enhancement could not be observed in 2 weeks of diabetes. In addition, after 8 weeks diabetic rats had significantly higher glycated Hb(GHb). Conclusion Gene expression of RAGE in renal tissue of diabetic rats is altered and the excessive gene expression of RAGE may enhance the AGEs-RAGE interactions which would contribute to the development of diabetic nephropathy. Furthermore, this change occurs as a result of hyperglycemia-induced AGEs formation.