Macrophages have been identified to play an important role in acute and chronic renal injury through exerting multiple biological effects.This review focus on the origin of macrophages in kidney, mechanism of renal injury and strategy of inhibiting macrophage infiltration. [

AIM A&A treated PAN rats, and to observe the effects of A&A on MAPK signaling pathway. METHODS Rats were divided into control, PAN, A&A treated PAN (A&A) and enapril treated PAN (ACEI) groups. The pathological lesion was observed under a light microscope. Immunohistochemistry combined with semi quantitive method was used to investigate the following parameters: cell number, ? SMA expression and extracellular matrix deposition. Expression and phosphorylation of protein kinases ERK, JNK and p38 were assayed. RESULTS In PAN rats, A&A suppressed ? SMA expression, which was closely correlated to cell proliferation, and extracellular matrix accumulation in glomerular mesangium. A&A significantly attenuated ? SMA expression in the tubulo interstitial area which was also parallel to the renal interstitial fibrosis.In this study, expression of all subtypes of MAPK had no difference between control and PAN groups. Compared with the inactivation of ERK and p38, phosphorylation of JNK was observed in glomeruli, renal tubules and interstitial cells in PAN rats, which was also inhibited by A&A treatment. CONCLUSION The inhibitory effect of A&A on phenotypic changes of renal resident cells, especially glomerular mesangial cell, may participate in its renal protective mechanisms. This effect, at least partially, was mediated by down regulated JNK activation.

AIM: To compare the renoprotective effects of angiotensinⅡtypeⅠreceptor antagonist (AT 1RA) with that of angiotensin converting enzyme inhibitor (ACEI) and to investigate their influences on intrarenal renin-angiotensin system. METHODS: Experimental nephrotic syndrome model was induced in SD rats with repeated peritoneal injections of puromycin. Twenty-eight rats were randomly divided into four groups: normal control, nephrotic control, ACEI-treated and AT 1RA-treated group. Serum, urine and renal tissue were collected for study 12 weeks later. RESULTS: The urine protein was less and renal function was better in both treated groups. The glomerular and interstitial injury indexes of both ACEI and AT 1RA treated rats were lower than that of nephrotic control rats and had no significant difference between the two treated groups. The renal local ACE activity and angiotensinⅡ of nephrotic control group were significantly higher than that of normal control group and the two treated group(P

AIM: To investigates the role of phosphatidic acid (PA) in the expression of several inflammatory mediators produced by glomerural macrophages (GM?). METHODS: The study was performed on a rat model of accelerated anti-glomerural basement membrane (anti-GBM) glomerulonephritis (GN). GN-GM? were isolated and identified. Peritoneal M? (P-M?) of both normal and GN rats were used as controls. Block and reverse test were investigated with rhIL-1? stimulated, lisofylline (LSF) and phosphatidic acid (PA). Macrophage expression of ICAM-1 and TGF-? 1 were assessed at the level of protein and gene by immunocytochemistry, northern blot and RT-PCR. RESULTS: (1) After stimulated with rhIL-1?, GN-GM? produced much more ICAM-1, MCP-1 and TGF-? 1 than P-M?, and it's gene expression was similar as protein product. (2) mRNA expression of these factors was up-regulated again after the GN-GM? were pretreated with LSF then PA was added. CONCLUSIONS: Since GN-GM? plays an important role for PA in the mediation of glomerular injury, inhibiting of PA production is the keypoint of blocking M? mediated inflammatory effects. LSF may be an effective medicine in therapy for acute inflammatory forms of GN.

Objective: To investigate peroxisome proliferator activated receptor ? (PPAR ?) expressions in patients with actively proliferating glomerulonephritis such as type Ⅳ lupus nephritis (LN) and cellular crescentic glomerulonephritis (RPGN). Methods: All patients were divided into 4 groups as follows: RPGN (17 cases); LN type Ⅳ (15 cases); mild mesangial proliferative IgA nephropathy (IgAN, 7 cases) and minimal change disease (MCD, 10 cases). Clinical parameters, immunohisto chemistry stain and in situ hybridization of renal biopsy specimens were performed. Results: Clinically, proteinuria and hematouria were increased and Ccr were decreased in LN and RPGN patients, and increased ESR and decreased complement C3 were found in group LN. Active index of renal specimens were significantly higher in LN and RPGN groups than in IgAN and MCD groups. Renal specimens of MCD patients showed no positive PPAR ? staining in all sections; little immunoreactivity was detected in sections of glomerular, tubular and interstitial cells from IgAN patients. Glomerular positive staining of PPAR ? in renal sections in LN and RPGN patients[(3.3?1.8) and (2.8?1.2) cells per section of glomerulus, respectively] were significantly increased compared with that in IgAN patients [(0.7?0.5) cells per section of glomerulus]. Similarly, tubular positive staining of PPAR ? in LN and RPGN patients (27.38? 12.46, 23.36?10.55) were also elevated compared with that in IgAN and MCD patients(6.51?3.49, 1.72?0.31). The relevance assay results showed positive relationship between active index and glomerular or tubular PPAR ? immunohisto chemistry staining cell numbers (0.478, P

Objective To study the whole genome DNA methylation changes induced by low dose radiation (LDR) in mouse,and mRNA expression profiles of DNMT1 and MBD2 in peripheral blood mononuclear cell (PBMC) and tissues.Methods Thirty male BALB/c mice were randomly divided into 3 groups:control,single exposure (0.5 Gy),and fractionated exposure of 6 MV X-rays for 10 d (0.05 Gy/d × 10 d).Control mice were sham-treated.To determine the immediate (early) effect of irradiation,15 mice (5/group) were sacrificed 2 h after the last irradiation.The other 15 mice were sacrificed 1 month after the last irradiation (delayed effect).Before sacrifice,blood was sampled immediately.Kidney,liver,spleen,brain and lung tissues were collected.A global DNA methylation quantification Kit and highperformance liquid chromatography (HPLC) were used to investigate the methylation level in blood DNA.The expressions of DNMT1 and MBD2 were determined by RT-PCR.Results For the early effects of irradiation,as compared with controls,fractionated exposure to X-ray irradiation led to the significant depression of global DNA methylation level in blood (t =10.19 and 8.93,P ＜ 0.05).DNMT1 and MBD2 mRNA were down-regulated in PBMC,kidney and liver (t =5.06,3.01,3.97,12.25,3.50 and 3.73,P ＜0.05),and MBD2 was also down-regulated in spleen (t =3.03,P ＜ 0.05).However,no changes were observed in single exposed group.As for the delayed effects,the methylation levels of blood were not changed in the single or fractionated exposed groups,and only MBD2 mRNA was down-regulated in PBMC and brain of fractionated exposed group (t =3.52 and 2.85,P ＜ 0.05).Conclusions Fractionated LDR exposure can induce genome DNA hypomethylation,which is tissue-specific,and may be related with down-regulation of DNMT1 and MBD2.

OBJECTIVE To study the effect of different concentrations of 17-AAG and EGCG monotherapy or in combination on the induced apoptosis in human nasopharyngeal carcinoma, and to explore new molecular targets for the treatment of nasopharyngeal carcinoma. METHODS MTT colorimetric method and fluorescent staining were used to detect the change of CNE proliferation inhibition rate and cell morphology. And furthermore, the expression level of Bcl-2, Bax, Caspase-3 were detected by RT-PCR. RESULTS 1. 17-AAG or EGCG alone had inhibitory effect on the human nasopharyngeal carcinoma CNE cells at 24 h, 48h and 72 h, and it was related with time and dose(P<0.01). The inhibition effect of combination of 17-AAG and EGCG was significantly increased,which was time and dose dependent(P<0.01). 2. RT-PCR was used to detect the mRNA expression level of Bcl-2, Bax and caspase-3. The level of Caspase-3 and Bax mRNA expression after treated by 17-AAG and EGCG was significantly higher, and the level of bcl-2 mRNA expression was lower than that after treated by 17-AAG or EGCG alone. CONCLUSION Our investigation implied that 17-AAG and EGCG in combination can effectively inhibit the proliferation of human nasopharyngeal carcinoma CNE cells. The involved mechanisms may be associated with the upregulation of Bax and Caspase-3 expression.

AIM: To understand the expression of low density lipoprotein receptor-related protein (LRP) in tubulointerstitial fibrosis of unilateral ureter obstruction (UUO) rats. METHODS: The localization of LRP within kidneys were assessed by immunohistochemical staining, the protein level of LRP and connective tissue growth factor (CTGF) in kidney were analysised by Western blot. RESULTS: The location of LRP positive-staining and the protein level of LRP were in the same tendency with CTGF, the level of LRP had strong correlationship with the level of CTGF (r=0.786, P

AIM: To study the expression of connective tissue growth factor (CTGF) induced by hypoxia, and the role and mechanism of hypoxia on promoting renal interstitial fibrosis. METHODS: Renal interstitial fibrosis was induced by unilateral ureteral obstruction (UUO) in rat animal model for 9 days as in vivo studies; marker of hypoxia-HIF-1? mRNA and protein, the expression of CTGF in the obstructed kidneys were assessed by RT-PCR, immunohistochemistry and Western blotting respectively. In vitro , normal rat kidney interstitial fibroblast cells (NRK-49F) were exposed to hypoxia (1%O 2) for up to 6 hours, hypoxia was confirmed by detecting the expression of HIF-1? protein in cells, cellular level of CTGF mRNA and protein were assessed by RT-PCR and Western blotting respectively. RESULTS: Neither HIF-1? mRNA nor HIF-1? protein was expressed in the kidney from sham-operated group of rats. High level of HIF-1? mRNA were occurred, and strongly HIF-1? positive immunostaining were seen in the tubular and interstitial cells in kidney from UUO rats. Expression and location of CTGF protein were paralleled and relevant with the expression of HIF-1? protein in kidney of UUO rats. In cultured NRK-49F cell line, subjected to hypoxia even for 6 hours stimulated the expression of CTGF mRNA and protein. CONCLUSION: Our results indicated that hypoxia could stimulate the expression of CTGF mRNA and protein in kidney from UUO rats, which may in turn contribute to renal interstitial fibrosis.

OBJECTIVETo identify genes associated with the chronic progression of renal disease and a stragalus and angelica (A&A)'s renal protective effects.

METHODSThe technique of silver staining mRNA differential display (DD) was used to investigate changes of gene expression in normal, sclerotic and A&A treated sclerotic kidneys. We isolated genes differentially expressed during the progression of renal disease which could be normalized by A&A.

RESULTSSeveral genes related to A&A's protective effects were isolated and one of them was confirmed by Northern blot.

CONCLUSIONSilver staining mRNA differential display is a simple and effective technique for isolating differentially expressed genes. The isolated new gene may be related to the progression of chronic renal disease and contribute to A&A's protective effects.

Angelica sinensis ; Animals ; Astragalus Plant ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; drug effects ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; Phytotherapy ; Polymerase Chain Reaction ; Protective Agents ; pharmacology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling