Advances of aerobic glycolysis in renal interstitial fibrosis / 中华肾脏病杂志

Aerobic glycolysis is a metabolic process in which cellular energy production favors the low-efficiency energy-producing glycolytic pathway in the presence of sufficient oxygen, reducing dependence on aerobic respiration, while producing energy rapidly and providing advantages for cell survival and proliferation. In recent years, several studies have shown that aerobic glycolysis is involved in the development of renal interstitial fibrosis (RIF) and involves various cell types such as fibroblasts, endothelial cells, renal tubular epithelial cells, pericytes, and inflammatory cells. Drugs targeting glycolysis may provide new ideas for the prevention and treatment of RIF. This article reviews the research progress of abnormal aerobic glycolysis in different cells and glycolytic intervention drugs in RIF.

Preliminary Conception of Theory of Triple Energizer-nutrient-defense Loop / 中国实验方剂学杂志

The research on the essence of triple energizer has not reached a consensus. The correspondence between the existing understanding and the classical theory of triple energizer is still limited in terms of structure and function. According to the traditional theory， nutrient-defense takes channels as the main circulatory system， while the operation of nutrient-defense in the triple energizer remains unclear. Since little is known about the physical structure of the triple energizer， the role of triple energizer as a collection of other Zang-fu organs has been ignored in most cases. The new progress in anatomy paves the way for the research on the essence of triple energizer. The function and structure of triple energizer are similar to those of interstitium and interfacial fluid flow， which enriches our understanding of the macro and micro structures of triple energizer. The triple energizer is distributed throughout the body and composed of membrane and interstitial space. The material structure of triple energizer includes fiber scaffold， collagen fiber， mesenchymal stem cells， histiocytes， pericytes， and interstitial fluid. The functions of triple energizer include passing body fluids， operating nutrient-defense， distributing original Qi， and transmitting and changing pathogenic Qi. According to the available theories and research achievements， we put forward the concept of vertical and horizontal triple energizer， pointed out that triple energizer had independent structure and the features of Zang-fu organs， and preliminarily defined the spatial distribution of triple energizer. The relationship between channels and triple energizer is essential for discussing the operation of nutrient-defense. Telocyte （Tc） and telopod （Tp） has the characteristics of channels in function and structure. The connective tissue with the distribution of Tc and Tp belongs to the same material as the basic structure of interstitial/interfacial fluid flow system and the fibrous skeleton of interstitium. It is clear that channels and triple energizer have material commonality. From the operation paths of nutrient-defense， we proposed that channels may be soaked and attached in triple energizer and put forward the model of channels soaked and attached in triple energizer. By combining the circulation of nutrient-defense with the vertical and horizontal triple energize， we developed the theory of triple energizer-nutrient-defense loop to comprehensively describe the generation， transport， and metabolism of nutrient-defense in channels and triple energizer， aiming to provide a theoretical model for future studies of disease transmission and change from exterior to interior.

Preliminary Conception of Theory of Triple Energizer-nutrient-defense Loop / 中国实验方剂学杂志

The research on the essence of triple energizer has not reached a consensus. The correspondence between the existing understanding and the classical theory of triple energizer is still limited in terms of structure and function. According to the traditional theory， nutrient-defense takes channels as the main circulatory system， while the operation of nutrient-defense in the triple energizer remains unclear. Since little is known about the physical structure of the triple energizer， the role of triple energizer as a collection of other Zang-fu organs has been ignored in most cases. The new progress in anatomy paves the way for the research on the essence of triple energizer. The function and structure of triple energizer are similar to those of interstitium and interfacial fluid flow， which enriches our understanding of the macro and micro structures of triple energizer. The triple energizer is distributed throughout the body and composed of membrane and interstitial space. The material structure of triple energizer includes fiber scaffold， collagen fiber， mesenchymal stem cells， histiocytes， pericytes， and interstitial fluid. The functions of triple energizer include passing body fluids， operating nutrient-defense， distributing original Qi， and transmitting and changing pathogenic Qi. According to the available theories and research achievements， we put forward the concept of vertical and horizontal triple energizer， pointed out that triple energizer had independent structure and the features of Zang-fu organs， and preliminarily defined the spatial distribution of triple energizer. The relationship between channels and triple energizer is essential for discussing the operation of nutrient-defense. Telocyte （Tc） and telopod （Tp） has the characteristics of channels in function and structure. The connective tissue with the distribution of Tc and Tp belongs to the same material as the basic structure of interstitial/interfacial fluid flow system and the fibrous skeleton of interstitium. It is clear that channels and triple energizer have material commonality. From the operation paths of nutrient-defense， we proposed that channels may be soaked and attached in triple energizer and put forward the model of channels soaked and attached in triple energizer. By combining the circulation of nutrient-defense with the vertical and horizontal triple energize， we developed the theory of triple energizer-nutrient-defense loop to comprehensively describe the generation， transport， and metabolism of nutrient-defense in channels and triple energizer， aiming to provide a theoretical model for future studies of disease transmission and change from exterior to interior.

Convergence of Medicines: West Meets East in Newly-Discovered Organs and Functions / 中国结合医学杂志

Although the foundations and evolution of Chinese medicine and Western medicine are very different, an increasing amount of research has revealed that those Eastern medicine principles practiced over thousands of years are confirmed by new technologies applied to the basic science of the human body. Recent scientific discoveries present enticing opportunities to reconcile Chinese medicine theories with Western biomedicine. Is there a trend toward the convergence of Eastern and Western medicine? Four studies which exemplify the potential for convergence are described in this article. The studies present findings in regard to mesentery, interstitium, a gut-lung axis, and lung-centered hematopoiesis, and were published recently in leading journals such as Science, Nature, and Lancet.

Molecular mechanism of miR-382 in the pathogenesis of renal tubulointerstitial fibrosis / 中华肾脏病杂志

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF).Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity,as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1),which was further verified by 3'-untranslated region luciferase assay and site-directed mutagenesis.The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model.Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO,and repeated the dosage 24 h after the surgery.For clinical verification,renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected,6 patients with moderate to severe TIF and 6 patients without TIF.The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry.Results HSPD1 was confirmed to be a new,direct target gene of miR-382 by in vitro 3'-untranslated region luciferase assay and sitedirected mutagenesis.The development of epithelial transition in HK2 cells was accompanied with upregulation of miR-382 [(6.54±0.96) vs (1.12±0.26),P ＜ 0.05].Blocking the expression of miR-382 could reversed the progression of epithelial transition partially.In UUO mice the abundance of miR-382 was up-regulated [(6.89 ± 2.47) vs (1.00±0.42),P ＜ 0.01] while HSPD1 and Trx were downregulated compared with the sham group.Down-regulation of miR-382 was associated with significant decrease in TIF,but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1:(0.34±0.10) vs (0.14±0.05);Trx:(0.79±0.18) vs (0.36±0.16);all P ＜ 0.05].The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF.Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice.HSPD1 is one of the target genes of miR-382.The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.

Changes in the Testis Interstitium of Rabbits from Birth to Sexual Maturity / 체질인류학회지

Changes in the testis interstitium from birth to adulthood were studied in New Zealand white rabbits of 1, 7, 21, 35, 49, 70, 105, 147, 196, and 252 days (n=8 per group) of age. Testes of rabbits were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using 1 microm sections stained with methylene blueazure II, qualitative and quantitative (stereological) morphological studies were performed. Sperm production was measured by routine technique. The volume density of the interstitium represents 66.3% of the testicular parenchyma at day 1. Adult Leydig cells initially detected at day 7 (0.001%), increased progressively to reach a volume density of 2.6% by day 252. The absolute volume of mesenchymal cells, endothelial cells, pericytes, and myoid cells increased from birth to 252 days. The number of endothelial cells, pericytes, and myoid cells per testis increased gradually with age. The absolute numbers of adult Leydig cells and mesenchymal cells per testis increased linearly from birth to 252 days. The rate of production of adult Leydig cells was greater than that of mesenchymal cells in the postnatal rabbit testis through 252 days. The average volume of a mesenchymal cell increased from day 1 to day 70 and declined thereafter; the highest value was at day 70. Total sperm production and daily sperm production per testis increased significantly from 105 to 252 days of age. These results clarified the pattern of changes in the testis interstitium in rabbits from birth to adulthood and correlation these events with spermatogenesis.

Changes in the Testis Interstitium of Rabbits from Birth to Sexual Maturity / 체질인류학회지

Changes in the testis interstitium from birth to adulthood were studied in New Zealand white rabbits of 1, 7, 21, 35, 49, 70, 105, 147, 196, and 252 days (n=8 per group) of age. Testes of rabbits were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in Epon-araldite. Using 1 microm sections stained with methylene blueazure II, qualitative and quantitative (stereological) morphological studies were performed. Sperm production was measured by routine technique. The volume density of the interstitium represents 66.3% of the testicular parenchyma at day 1. Adult Leydig cells initially detected at day 7 (0.001%), increased progressively to reach a volume density of 2.6% by day 252. The absolute volume of mesenchymal cells, endothelial cells, pericytes, and myoid cells increased from birth to 252 days. The number of endothelial cells, pericytes, and myoid cells per testis increased gradually with age. The absolute numbers of adult Leydig cells and mesenchymal cells per testis increased linearly from birth to 252 days. The rate of production of adult Leydig cells was greater than that of mesenchymal cells in the postnatal rabbit testis through 252 days. The average volume of a mesenchymal cell increased from day 1 to day 70 and declined thereafter; the highest value was at day 70. Total sperm production and daily sperm production per testis increased significantly from 105 to 252 days of age. These results clarified the pattern of changes in the testis interstitium in rabbits from birth to adulthood and correlation these events with spermatogenesis.

Correlation of Notch1 receptor expression in renal tissue of hepatitis B virus associatedglomerulonephritis with clinicopathology / 中华肾脏病杂志

Objective To investigate the expression of Notch 1 receptor in renal tissues of patients with hepatitis B virus associated-glomerulonephritis (HBV-GN) and its role in the pathogenesis of HBV-GN.Methods A total of 48 patients with HBV-GN confirmed by renal biopsy during 2008-2010 were enrolled in the study.Distribution of Notch1 receptor in renal tissue of HBV-GN was detected by immunohistochemistry and the association between the distribution of Notch1 receptor and HBsAg was examined by double-label immunofluorescence assays.Correlations of Notch1 receptor expression with renal pathology and clinical parameters of HBV-GN were analyzed.Results Notch1 receptor distributed mainly in renal tubular epithelial cells and interstitial area as brownish red granules,and a few expression in glomerulus was also found.The positive score of Notch1 receptor expression in HBV-GN patients was significantly higher as compared to primary glomerulonephritis patients with serum HBsAg positive or negative and normal renal tissue controls.Notch1 receptor expression was more obvious in membrano-proliferative glomerulonephritis (MPGN) and mesangial proliferative nephritis (MsPGN) patients,but there was no significant difference among the different pathology groups.Distribution of Notch1 receptor was consistent with the distribution of HBsAg and its intensity was positively correlated with renal interstitial fibrosis (r=0.473,P=0.001),tubular atrophy (r=0.690,P=0.000),inflammatory cell infiltration (r=0.616,P=0.000).Negative correlation was found between renal function and the intensity of Notch1 receptor (r=-0.393,P=0.006).Conclusions Notch1 receptor expression increases in the renal tissues of HBV-GN patients and distributes mainly in renal tubular epithelial cells and interstitium,which is consistent with the distribution of HBsAg.Its intensity is closely correlated with renal interstitial lesions and renal function.Abnormal expression of Notchl receptor in renal tissue of HBV-GN may be involved in the progress of HBV-GN.

Effects of valsartan on renal interstitium fibrosis in rats after unilateral ureteral obstruction / 第二军医大学学报

Objective To study the effect of valsartan, an angiotensin II type I receptor antagonist AT1RA), on renal interstitium fibrosis(RIF)in rats with unilateral ureteral obstruction (UUO), and to discuss the possible mechanisms. Methods Thirty-five Sprague-Dawley rats were randomly divided into sham-operation, model and valsartan groups. The rat UUO model was established. From the day after operation, the rats in sham-operation and model groups received intragastric valsartan and sodium chloride in tales doses. The serum creatinine (SCr), blood urea nitrogen (BUN), angiotensin- II (Ang II ) in blood plasma, N-acetyl-β-D-glucosaminidase(NAG)and 24 h urine β2-microglobulin(β2-MG)were examined 4 weeks after operation. The renal tissues of the obstructed sides were harvested; H-E staining and Masson staining were used to observe the tubulointerstitial lesions; and immunohistochemistry staining was used for semiquantitative analysis of alpha-smooth muscle actin(α-SMA), fibronectin(FN), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta 1 (TGF-β1), and hepatocyte growth factor(HGF). Results Compared with those in the sham-operation group, SCr, BUN, Ang II, NAG and (β2- MG levels, and the expression of α-SMA, FN, PAI-l, and TGF-β1 in model group were significantly higher(P0. 05). The expression levels of orSMA, FN, PAI-l, and TGF-β1 in valsartan group were significantly lower than and the expression of HGF was significantly higher than those in the model group(P<0. 01). Conclusion Valsartan does not improve the tubular and glomerular functions, but it can inhibit production of Ang-II. Valsartan may inhibit renal interstitial fibrosis by inhibiting renal tubule epithelial mesenchymal transdifferentiation and reducing extracellular matrix deposition through blocking up Ang Q, inhibiting overexpression of α-SMA, FN, PAI-l, and TGF-β1, and inducing the HGF expression.

Collagen type Ⅲ is an important linking molecule between generated renal tubules and an artificial polyester interstitium Reticulin as a linker between generated tubules and the interstitium / 中国组织工程研究

In the field of regenerative medicine,much consideration has been given to stem/progenitor cells for the future treatment of acute and chronic renal failure.For this strategy to be effective,however,cell biological information about tubule development within the diseased organ is needed.Unresolved cell-biological issues relating to this kind of treatment include①the integration of stem/progenitor cells,②their differentiation into site-specific cell types,and③the spatial formation of new tubules.To better understand the mechanisms related to this technology,renal tubules were generated at the interphase of an artificial interstitium by using advanced culture techniques.Stern/progenitor cells derived from neonatal rabbit kidney were covered with layers of polyester fleece,placed in a perfusion culture container,and superfused for 13 days with fresh and chemically defined Iscove's Modified Dulbeccos Medium(IMDM) containing aldosterone (1×10-7mol/L).The spatial growth of tubules was registered by scanning electron microscopy(SEM) and on whole mounts or cryosections labeled with soybean agglutinin,silver stain and monoclonal antibodies reacting with collagen type Ⅲor laminin γ1.SEM revealed that the generated tubules were completely covered by a basal lamina.The lamina fibroreticularis exhibited numerous fibers connecting the basal aspect of generated tubules with the surrounding polyester fibers.Cryosections labeled with monoclonal antibodies anti-collagen type Ⅲ and silver stain demonstrated the formation of numerous fibers spanning between the basal lamina of generated tubules and neighboring polyester fibers.In matured kidney tubules the samg arrangement of collagen type Ⅲ fibers is observed as that for generated tubules.This work shows that collagen type Ⅲ is a relevant molecular linker between the basal aspect of generated renal tubules and the polyester fibers of the artificial interstitium.

Role of JAK-STAT signaling in the interstitial fibrosis of unilateral ureter obstruction mice / 中华肾脏病杂志

Objective To study the role of JAK-STAT singal transduction pathway in the interstitial fibrosis of unilateral ureter obstruction (UUO)mice. Methods Mice UUO model was established and the phosphorylation of JAK-STAT was examined at day 1,4,7 and 14 after ligation of the ureter.Mice in the treatment group were treated with daily injection of selective JAK2 inhibitor AG490 starting 2 h before ureter ligation until sacrifice while vehicle alone was given to mice in the model control group.Mice were sacrificed at day 14 after the establishment of model.Renal tubular lesion and interstitial fibrosis were assessed on paraffin section.Immunohistochemistry was used to detect renal macrophage infihration and α-SMA expression.The expression of collagen Ⅲ and MCP-1 mRNA was measured by RT-PCR.Phosphorylation of JAK2and STAT1 was examined by Western blotting. Results JAK2-STAT1 signaling transduction pathway was activated in UUO model.The activation of JAK2-STAT1 was closely correlated with the progression of renal injury,tubular histological lesions and interstitial fibrosis.AG490 treatment significantly inhibited the phosphorylation of JAK2 and STAT1 (P＜0.01).AG490 treatment also significantly reduced tubular lesions[(21.7 ±1.7)% vs (49.4±1.0)%]and interstitial fibrosis(1.0±0.1 vs 2.3±0.2),α-SMA expression(0.9±0.1 vs 2.1±0.2)and maerophage accumulation[(13.3±1.6)cells/HPF vs (34.4±1.0)cells/HPF](all P＜0.01).In addition,AG490 significantly inhibited the expression of collagen Ⅲ and MCP-1 mRNA. Conclusion JAK-STAT signaling plays an important role in renal tubulointerstitial inflammation and fibrosis.

The peritubular microangiopathic lesions caused by aristolochic acid and the expression of vascular endothelial growth factor in rats / 解放军医学杂志

Objective To investigate the pathological characters of capillaries in tubulointerstitial nephropathy,and to study the expression of vascular endothelial growth factor(VEGF)and proliferation cell nuclear antigen(PCNA)in capillary endothelial cells in aristolochic acid-induced nephropathy in rat.Methods 46 male Wistar rats were randomly divided into 2 groups,the model group was composed of 26 rats which were gavaged with the extract of Caulis Aristolochiae Manshuriensis(aristolochic acid AA 20mg/kg?d),and the control group consisted of 20 rats which were treated with equal volume of potable water.The rats were sacrificed in batches at the end of 4th,8th and 12th weeks,and the blood samples were collected from abdominal aorta for the tests of renal functions.The kidney of each rat was harvested.The renal tissues were stained with HE,PAS,and Masson's technique for the analysis of degree of tubulointerstitial injury,interstitial fibrosis,and peritubular capillary(PTC),and the expressions of both VEGF and PCNA were morphologically observed and immunohistochemically analyzed.Results In the model group,the level of serum creatinine/body weight increased markedly,the renal pathological changes consisted of severe acute renal tubulointerstitial damage with cloudy swelling of tubule,degeneration,and exfoliation.With prolongation of feeding time,the damage progressively aggravated,and showed a remarkable tubulointerstitial injury.The interstitial fibrosis area was 31.36% at the end of 12th week.The renal capillaries showed thickening of vessel wall,narrowing of the vessel cavity,obstruction or hyalinization of some capillaries.There was focal infiltration of inflammatory cells around the injured vessels.But there was no apparent change in the globules compared with that in control group.The PTC dwindled in caliber or distorted,and the PTC density decreased significantly in models,especially in the region of tubular damage or interstitial fibrosis.The expression of VEGF showed compensatory up-regulation at the 4th week,but it was down-regulated gradually.The expression of PCNA was up-regulated at the 4th week,but down-regulated after 8th week,and only a few basement membrane naked tubular cells showed positive expression at 12th week.Conclusion AA could induce injury and loss of capillaries of the kidney.The decrease in capillary density might contribute to the impairment of renal function and progressive interstitial fibrosis,and the relative deficiency of VEGF expression may be related to PTC injury,which is one of the causes of chronic progression of aristolochic acid nephropathy.

Experiment studies on renal damage, tubular-interstitial fibrosis and the expression of related factors in rats' aristolochic acid nephropathy / 解放军医学杂志

Objective To study the tissue pathology and the expression of related factors during renal tubular-interstitial fibrosis in aristolochic acid (AA) nephropathy in rat. Methods 46 male Wistar rats were randomly divided into 2 groups. The test group consisted of 26 rats which were gavaged with the extract of Caulis Aristolochiae Manshuriensis (CAM) (AA 20mg?kg -1 ?d -1 ); the control group consisted of 20 rats which were given with equal volume of potable water. At the end of 4th, 8th, 12th week, the kidneys of each rat were separately harvested. The HE, PAS and Masson staining were used to analyze the degree of tubular damage and interstitial fibrosis, and immunohistochemical method was applied to assess the protein expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), transforming growth factor-?_1 (TGF-?_1) in the renal specimens. The mRNA expression of VEGF, endothelin-1 (ET-1), bone morphogenetic protein-7 (BMP-7) in renal tissue were determined by RT-PCR respectively. Results A severe renal tubular-interstitial damage and an early fibrosis were observed at the end of 12th week, and the interstitial fibrotic area was 31.36%. The protein expression of PCNA was increased at 4th week, but down-regulated after 8th week; the expression of TGF-?_1 and VEGF was increased at 4th week, while TGF-?_1 was maintatined on a high level with passage of time, but VEGF decreased gradually. The mRNA expression of VEGF and ET-1 increased notably at 4th week, slightly decreased after 8th week, but maintained at a high level. The BMP-7 declined slowly with the progression of pathological changes, reaching its lowest level at 12th week. Conclusion The mechanism of the rapid progression of fibrosis in AAN might be the renal result of severe impairment of regeneration of epithelial cells, lowering of expression of factors of promoting repair and inhibiting fibrosis, while the expression of factors of promoting fibrosis was maintained at a highlevel.

Action of NF-?B p65 in renal interstitium in rats with active Heymann nephritis / 中国病理生理杂志

AIM: To study the action of NF-?B p65 in tubule-interstitium in rats with active Heymann nephritis(AHN). METHODS: Twenty female Wistar rats in 6-8 weeks of age were divided into two groups. The nephritis was induced with Fx1A/CFA by subcutaneous injection and with CFA as control. After rats were killed, the activation of NF-?B p65 in renal tissue was observed by immune histochemistry. RESULTS: The lesion score of renal interstitium and activation of NF-?B p65 of renal tubule in rats with AHN was higher than those of control group(P

Morphometric Study of the Testicular Interstitium of the Rat during Postnatal Development / 대한해부학회지

The purpose of this morphometric study was to obtain quantitative information on the rat testis interstitium during postnatal development. Eight groups of male rats aged 1, 7, 14, 21, 28, 40, 60 and 90 days (n=5 rats per group) after birth were used. Tissue from perfusion-fixed testes was embedded in Epon-Araldite; and sections were subjected to morphometric measurements at the light microscopic level, using point counting method for volume densities and the Disector technique for numerical densities (the number of cells per unit volume of testis). The volume density of the interstitium represents 66% of the testicular parenchyma at day 1. This proportion progressively diminishes during development to reach a value of 8% at day 90. The absolute volume of blood vessels, macrophages, and endothelial cells increased with age. The absolute volume of lymphatic spaces, pericytes and myoid cells were greater at 90 days than at any other age. The absolute volume of fetal Leydig cells per testis was unchanged from 1 (0.07 mm3) to 14 (0.1 mm3) days, despite a decrease in the volume density. The number of mesenchymal cells, myoid cells, macrophages, endothelial cells, and pericytes per testis increased with age. The number of fetal Leydig cells per testis did not change from days 1 (0.054 million)~21 (0.070 million) although on day 21 (615 micrometer3) an average fetal Leydig cells was smaller in volume than at earlier ages (days 1 (1338 micrometer3)~14 (1296 micrometer3)). Adult Leydig cells were recognized at day 14 and their absolute volume and number per testis increased from 14 (0.5 mm3, 0.6 million) to 90 (52.83 mm3, 21.14 million) days. The average volume of a adult Leydig cell increased significantly with age and reached maximum size by 60 days (2548 micrometer3) of age where the volume is nearly three times bigger than that of at day 14 (832 micrometer3). No change in the average volume of the macrophages could be detected in this study groups. The average volume of the mesenchymal cells decreased significantly from day 1 (812 micrometer3) to day 14 (385 micrometer3) then increased until day 28 (901 micrometer3) at which the volume is maximum and declined significantly thereafter.

The Efficacy of N-acety1-beta-D-glucosaminidase as a Prognostic Factor of Glomerulonephritis / 대한신장학회잡지

BACKGROUNDS: N-acetyl-beta-D-glucosaminidase (NAG) is one of many enzymes that exist in the renal proximal tubular cells. It is said that functional impairment of renal tubule can be detected by checking NAG in the urine. But, it has never been known whether urinary NAG value can be used as a predictor for the prognosis of patients with glomerulonephritis. In this study, we evaluated the relationship between urinary NAG level and the degree of injury in cortical interstitium which has been known to influence the prognosis of renal function in glomerulonephritis closely. METHODS: Before renal biopsy was performed in each patient, urinary NAG(isoenzyme A and B), urinary beta2-microglobulin, serum blood urea nitrogen (BUN), serum creatinine, serum albumin, creatinine clearance and 24 hour urinary protein excretion were measured. Then, we calculated volume density of cortical interstitium [Vv(i/c)] in each specimen using point count morphometry method after getting a confirmative diagnosis from pathologist. Simple correlation analysis and multivariate regression analysis were carried out. RESULTS: The number of total patients was 32(male:16), whose median age was 60(32-80). Vv (i/c) had significant correlation with serum creatinine, creatinine clearance and serum BUN. But it was not correlated well with urinary NAG and urinary beta2-microglobulin. Urinary NAG concentration(2.131 2.549unit/mmol Cr) was higher than that of normal control and showed significant correlation with urinary beta2-microglobulin, serum albumin and 24 hour urinary protein excretion in patients. CONCLUSION: Urinary NAG had no significant correlation with Vv(i/c) that has been known as an important prognostic factor for the renal function in glomerulonephritis, but had significant correlation with urinary protein excretion. We concluded that urinary NAG was not regarded to be an appropriate marker for predicting the prognosis of renal function in patient with glomerulonephritis.

Experimental study on renal interstitial fibrosis of chronic aristolochic acid nephropathy in rats / 中华肾脏病杂志

Objective To establish a model of chronic aristolochic acid nephropathy (CAAN) in rats and to investigate the pathogenesis of its renal interstitial fibrosis.Methods Male Sprague-Dawley rats were randomly divided into two groups. One group received extract of Aristolochia manshuriensis Kom by gavage intermittently as model group. Another group received only tap water by gavage as controls. Six rats in each group were sacrificed at the end of 4th, 8th and 12th week respectively and the kidneys of each rat were separately harvested. The mRNA and protein expression of type I collagen (Col I ), transforming growth factor-?1 (TGF-?1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was detected by real-time quantitative RT-PCR and immunohistochemical staining respectively. Results The mRNA expression of Col I, TGF-?1, CTGF, PAI-1 and TIMP-1 in kidney tissue of the rats in model group was significantly upregulated compared to that in controls at the end of 4th week (9.31-, 5.16-, 1.79-, 8.66- and 2.54-fold, respectively) (P

Study on transdifferentiation of renal tubular epithelial cells in patients with chronic aristolochic acid nephropathy / 中华肾脏病杂志

Objective To investigate the relationship between tubular cells transdifferentiation and renal interstitial fibrosis in patients with chronic aristolochic acid nephropathy (CAAN). Methods Specimens from renal biopsies of 10 CAAN patients with serum creatinine level of (309. 41 ? 164. 44) ?mol/L were performed to examine the extent of renal interstitial fibrosis by Masson staining, the expression of collagen types Ⅰ and Ⅲ by sirius red staining, and the expression of cytokeratin(CK), ?-smooth muscle actin (a-SMA), vimentin (Vim) and transforming growth factor-? 1 (TGF-?1) by immunohistochemical staining. Quantitative analysis by computer image analytic system or semi-quantitative analysis were used to evaluate the data. Results There was positively significant correlation between interstitial collagen types Ⅰ and Ⅲ and serum creatinine level ( r =0. 890, P

Expression of cell cycle regulatory proteins in renal tubulointerstitial cells of human glomerulo- ncphritis / 中华肾脏病杂志

Objective To examine the expression of cell cycle regulatory protiens in renal tubulointerstitial cells of human glomerulonephritis. Methods Immunohisochemieal studies were performed on 19 specimen from renal biopsy to detect cyclin Dl, cyclin A, p21 and proliferating nuclear antigen (PCNA) . Results Cyclin Dl, cyclin A and p21 were positive in some of tubulointerstitial cells, and showed significant correlations with positive PCNA cells. The numbers of tubular positive cells in both groupsofⅠand Ⅱ degree of histopathological change were more than those of other groups. The numbers of interstitialpositive cells showed significant correlations with the degree of tubulointerstitial histopathological change and the value of urine NAG. Conclusion Cell cycle regulatory proteins regulate the proliferation of tubular and interstitial cells, and correlate with the interstitial fibrosis.

Effect of simvastatin on experimental interstitial fibrosis and its mechanism / 中华肾脏病杂志

Objective To evaluate the effect and mechanism of HMG-CoA reductase inhibitor simvastatin on experimental interstitial fibrosis. Methods Experiments on rat 5/6 nephrectomy chronic renal failure model and primary cultured renal interstitial fibroblast cells were conducted in this study. The cell proliferation, extracellular matrix, c-fos mRNA expression of rat interstitial fibroblasts were measured by MTT assay, immunohistochernitry, semi-quantitative reverse-transcript PCR methods, respectively. Results Serum cholesterol, triglyceride and creatinine of treated group were significantly reduced by simvastatin as compared with controls. No statistical significance in BUN was observed between untreated and simvastatin-treated rats. Histological examination revealed that simvastatin caused a reduction in the glomeruli with sclerosis. Tubulointerstitial injury paralleled the degree of glomerular damage. Simvastatin in a dose-dependent manner inhibited the proliferation of renal intersititial fibroblasts, decreased the secretion of lamimn( LN), and suppressed the expression of c-fos mRNA, as compared with normal controls. No obvious effect on hyaluronic acid( HA) secretion of fibroblasts was found. Conclusions Simvastatin is anti-proliferative in interstitial fibroblasts and decreases the secretion of laminin. This effect is exerted, at least in part, via inhibition of the c-fos and c-jun-dependent mitogenic pathway. Simvastatin may prevent interstitial fibrosis development and attenuate renal damage in uremic rats with hvperlipidemia.