Alterations in the balance between synthesis and degradation of extracellular matrix (ECM) and its remodeling may result in an accumulation of ECM molecules and lead to glomerulosclerosis. Recent studies have focused on the role of degradative systems, especially the roles of plasminogen activators/plasminogen activator inhibitors (PA/PAI), matrix metalloproteinases, and their inhibitors[GK2*4/5!2*4/5] (MMP/TIMP) in the initiation and pathogenesis of renal diseases. Previously, attention has been paid to the study of inhibitors of ECM degrading enzymes, such as PAI and TIMP. Recent researchs showed that there existed complex dynamic expressions of enzymes and their inhibitors. Although many studies have tried to elucidate the pathogenesis of renal diseases, the exact underlying mechanisms are still not completely understood. For better understanding of the mechanism of chronic progressive renal diseases, the underlying genetic and molecular regulation of each component of PA/PAI and MMP/TIMP systems should be elucidated in different renal physiological and pathophysiological processes. Future studies are needed to manipulate activity or expression of these proteinases in order to treat and/or prevent glomerular diseases.

The prevention and control of chronic kidney disease(CKD)and end-stage renal disease(ESRD)has become an important public health problem.This article has outlined the status,hazards,and problems in prevention of CKD and ESRD,briefly described the work having been done by the Chinese Society of Nephrology of the Chinese Medical Association,and proposed countermeasures for future prevention and treatment of ESRD,aiming at improving knowledge of the urgency of combating ESRD by the society,government,public,and medical staff in order to improve the prevention and treatment of ESRD in China.

Objective To introduce the current development of nephrology during the period of "Eleventh-Five-Year Plan" in PLA medical circles,to serve as a reference for the further development of nephrology in PLA.Methods Literature concerning nephrology published domestically and abroad in past 5years were retrieved,and the progresses,achieved domestically and abroad,especially in PLA,on new concept,diagnoses and therapy of common nephropathy,and clinical applications of new drugs and techniques were emphatically analyzed.Results Great progresses have been made during the period of "Eleventh-Five-Year Plan" on basic researches,clinical applications and substitution therapy in nephrology,and outstanding achievements have been acquired on basic and clinical researches of chronic nephropathy and acute renal injury,drug treatment of renal diseases and continuous renal replacement therapy.The PLA medical personnel participated in the formulation of "Diagnostic and Therapeutic Standard of Renal Diseases" ,furthered the academic exchanges between the military and civilian circles,both domestically and abroad.The academic level of PLA in nephrology was raised markedly with obvious features and preponderance.Conclusion During the period of "Twelfth-Five-Year Plan" ,the focus of nephropathy researches should be put on the enhancement of the ability of military health service,integrated control and comprehensive remedy of acute renal injury induced by combat wound,trauma and stress injuries.It is important to stably retain the superiority on basic and clinical researches of chronic nephropathy,acquire more achievements,make greater contributions to raising the professional level of diagnosis and treatment of kidney diseases.

Chronic kidney disease(CKD)is increasingly recognized as a global public health problem.Uncontrolled complications of CKD,especially cardiovascular diseases,contribute greatly to the premature death and unfavorable prognosis.Recent evidence shows that CKD complications may occur earlier than previously thought.CKD complications deserve early detection and active treatment.Periodical follow-up and regular check should be done to adjust the therapeutic condition.Clinical practice guideline or recommendation based on evidence-based medicine is essential for management of CKD complications.Personalized treatment should be considered to improve survival and quality of life,and to make patient return to society.

Animal model of aged rat nephrotoxicity was induced by i. p. administrationof gentamycin in a dose of 140mg/kg/day. Part of those rats were treated with CordycepsSinensis(CS), Epimedium(Ep) and Astragalus Membranaccus (AM) in form of decoc-tion per Os and others seryed as control. The results were summarized as. 1. The nephro-toxicity of gentamycin was aggrevated with age. CS, Ep and AM are effective drugs inpreventing the tdeular damage caused by gentamycin in rats. The pathological changes ofrenal tuoules of the rat groups which treated with CS, Ep and AM were less severe thanthat of the control. 2. CS, Ep and AM could prevent the decline of renal cortical Na~+-K~+-ATPase activity of aged rat induced by gentamycin.

Objective To explore the changes of E-cadherin expression in renal ischemia-reperfusion injury.Methods For the in vitro analysis of epithelial ischemia,confluent monolayers of MDCK cells growing in DMEM were depleted of ATP for 4 h by incubation in PBS (supplemented with 1.5 mM CaCl2 and 2 mM MgCl2) containing 10 ?M antimycinA.For the in vivo studies of epithelial ischemic injury,adult Sprague-Dawley rats were subjected to bilateral renal artery ligation.Renal pathological changes were measured by PAS stain.Location and expression of E-cadherin were detected by immunohistochemistry and western blot respectively.Results E-cadherin were primarily found in a linear pattern at the lateral portions of the plasma membrane in normal MDCK.After ATP depletion for 4 hours,the linear pattern altered and manifested by the appearance of intracellular staining.In invivo ischemia-reperfusion model rats,E-cadherin expression was changed from normal tubular epithelial cell basal membrane to cytoplasma.Western blot suggested that in sham-operated rats,E-cadherin was 120 ku lane vs 80 ku lane in ischemia for 60 min rats,while in ischemia for 45 min rats,both the 120 ku and 80 ku lanes were detected.Conclusion In renal ischemia-reperfusion,the location and expression of E-cadherin are obviously altered in vivo and in vitro study and E-cadherin are degradated as ischemia time prolongs.These changes may be the reason why tubular epithelial cell exfoliated from TBM in ischemia-reperfusion injury.

Objective To investigate the protective effects of low-molecular heparin and urokinase on glomerular inflammation. Methods Forty 3-month-old female Wistar rats were randomly divided into five groups with 8 rats in each group: normal control (NC) group; lipopolysaccharide (LPS) group; LPS and tranexamic acid (LT) group; LPS, tranexamic acid and low-molecular heparin (LTH) group; and LPS, tranexamic acid and urokinase (LTU) group. Fibrin deposition and CD11b positive cells were identified by immunohistochemical staining. Western blotting was used to determine the ICAM-1 expression. Results No fibrin depositions and CD11b positive cells were found in glomeruli of rats in NC group. Compared with NC group, fibrin deposit (9.1%?1.6%), CD11b positive cell (11.2?2.1) and ICAM-1 expressions (0.23?0.09) were significantly increased in L group (P0.05). Conclusion Both low-molecular heparin and urokinase can effectively decrease fibrin deposits and alleviate inflammation.

Objective To investigate the effects of the expression of integerin-linked kinase (ILK) on connexin 43 (Cx 43) in rat mesangial cells (RMCs). Methods RMCs were divided into three different groups (6 for each group): RMC group, ILK-con siRNA group and ILK-siRNA group. ILK siRNA was synthesized, and then transfected into RMCs by LipofectAMIN 2000. RMCs were transiently transfected with ILK-con siRNA, ILK-siRNA and lysed 24h later, and mRNA was then extracted and detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis using ILK and Cx43-specific primers, and an aliquot of protein from each sample was subjected to western blot analysis using ILK and Cx43 antibodies. Cells were seeded into 96-well plates (2?103 cells/well) and then transfected with ILK-con siRNA and ILK-siRNA. After incubation for 24, 48 and 72 hours, respectively, 20?l of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (5mg/ml) was added into each well and incubated for 4 hours. Subsequently, 150?l of dimethyl sulfoxide (DMSO) was added to each well to dissolve the formazan crystals, and the absorption at 492nm was measured. Results ILK mRNA and protein levels decreased by 30%-50% after being transiently transfected with ILK-siRNA, while Cx 43 mRNA and protein levels increased by 30%-40% and 60%-70%, respectively. The viabilities in ILK-siRNA infected RMCs at 24, 48 and 72 hours were significantly higher than that in ILK-con siRNA infected RMCs. Conclusion Inhibition of ILK pathway will up-regulate the expression of Cx 43 and the viability of RMCs, implying that the regulation of connexin 43 might possibly be achieved via ILK pathway.

Observing the effects of Arg-Gly-Asp-Ser(RGDS) peptides on the actin organization and apoptosis in human glomerular mesangial cells, in order to explore the interaction mechanism of extracellular matrix (ECM)-integrin receptor-cy-toskeleton. Methods The alterations of actin microfilaments in glomerular mesangial cells were observed under laser scanning confocal microscope. And DNA electrophoresis and flowcytometry were used for assessing apoptosis. Results After two hours of incubation with RGDS peptides, some of the attached glomerular mesangial cells began to round up, with a prominent marginaliza-tion of the actin microfilaments which were bundled in thick aggergates to one edge of the cell. Later these cells detached and floated in the culture medium.The above sequently-occuring changes showed a time-dependent pattern. After ten hours of incubation with RGDS peptide, most of the cells had detached, and features of apoptosis appeared in them, such as inter-nucleo-somal DNA fragmentation and decreased DNA content. Conclusion RGDS tetrapeptide can disrupt the organization of cytoplasmic actin mi-crofilament, inhibit the attachment of the cultured glomerular mesangial cells and cause apoptosis in them.

Objective To explore the role of type 1 plasminogen activator inhibitor (PAI-1 ) in mediating renal tubulointerstitial injury of patients with IgA nephropathy. Methods The mRNA and protein production of PAI-l in renal tubulointerstitium were defected using in stiu hybridization and immunohistochemistry. Detections of antigens of ?-smooth muscle actin(?-SMA) and proliferating cell nucleus antigen (PCNA) were also performed. Results PAI-l was normally expressed in the walls of vessels and distal tubules, but significantly increased in lesions of IgA nephropathy, including crescents, Bowman capsules and tubulointerstitial infiltrating cells. There was lithe expression of PAl-1 in the glomerular capillary tufts. The renal expression of PAI-l was significantly correlated with serum creatinine (P