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Objective To observe the effects of mesenchymal stem cells (MSCs) surface CXC chemokine receptor 4 over-expression on the repair of kidney after ischemia reperfusion (I/R) injury.Methods The MSCs were co-cultured with I/R injured renal cell homogenate supernatant.The MSCs surface CXCR4 and stromal cells derived factor-1 (SDF-1α) protein levels were detected by Western blot, chemotactic ability of MSCs to SDF-1 was investigated by transwell test.The I/R injured renal model was made and pathological changes were observed in control group, I/R group, MSCs injection group and CXCR4 neutralize antibody group.Renal CXCR4 protein expression was measured by immunofluorescence histochemistry, SDF-1α、 CXCR4、 hepatocyte growth factor (HGF) and epidermal growth factor (EGF) mRNA were detected by Real-time quantitative polymerase chain reaction (RT-PCR).Comparisons among multiple groups were performed using One-way analysis of variance, and comparisons between groups were carried out using independent-sample t-test.Results In vitro, the SDF-1α protein expression markedly increased in I/R injured renal tissue homogenate, but the difference was not significant between I/R group and CXCR4 antibody group (t =0.862, P =0.403).MSCs surface CXCR4 protein expression increased significantly after co-cultured with I/R injured renal tissue homogenate (F =95.957, t =10.166, P ＜ 0.01), and the chemotactic ability of MSCs to SDF-1 increased at the same time (F =82.459, t =6.826, P ＜ 0.01), the CXCR4 protein expression (t =13.657, P ＜ 0.01) and the chemotactic ability (t =12.662, P ＜0.01) could be decreased by CXCR4 neutralize antibody.In vivo, renal tubular structure was destroyed in I/R group.After MSCs injection, the renal pathological injury improved rapidly, but the improvement could be inhibited by CXCR4 antibody.The expression of SDF-1α mRNA and level of SDF-1a protein increased in I/R group, but there was no significant difference among different groups (F =1.909,P =0.173).MSCs injection markedly up-regulated the CXCR4 protein and mRNA expression (F =6.663, P =0.006).Following the increase in CXCR4 expression, the expressions of HGF mRNA (F =11.898,P ＜ 0.01) and EGF mRNA (F =5.309, P ＜ 0.05) increased gradually which could be restrained by CXCR4 antibody (t =5.312, t =4.310, P ＜ 0.01).Conclusions I/R injured renal microenvironment markedly increased the mesenchymal stem cells surface CXCR4 expression, and increased CXCR4 expression can induce MSCs chemotaxis and stimulate the secretion of renal protective growth factors paracrine promoting the repair of the kidney.
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Objective To investigate the role of Akt signal pathway on the expression of monocyte chemoattractant protein-1 ( MCP-1 ) and nuclear transcription factor-κB (NF-κB) in renal tubular epithelial cells (HK-2) stimulated by albumin and to explore the mechanisms of action. Method The HK-2 cells were incubated in the presence of albumin (5,15,30 mg/mL) with or without Ly294002 (an inhibitor of Akt). Expression of mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR).Expression of Akt and protein MCP-1 were assessed by Western blot. Electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-κB. q-test was used to evaluate the differences in means between groups. Results Compared with control group, the expression of MCP-1 mRNA remarkly increased. [Control group: 0.233 ±0.01; BSA(5 mg/mL) group: 0.285 ±0.04; BSA( 15 mg/mL) group:0.387 ± 0.02; BSA ( 30 mg/mL) group: 0.473 ± 0.05; BSA ( 30 mg/mL) + Ly294002 group: 0. 325 ±0.05, P ＜ 0.05 ]. The expression of MCP-1 protein in renal interstitum of operation group were remarkly increased too. [ Control group: 100 ± 15.1; BSA ( 5 mg/mL) group: 148 ± 19.3; BSA ( 15 mg/mL) group: 176±20.7; BSA(30 mg/mL) group: 263 ± 18.1; BSA(30 mg/mL) + Ly294002 group: 175 ± 18.0, P ＜0.05 ]. Albumin stimulated the expression of MCP-1mRNA and protein in a dose-dependent manner. Albumin remarkably increased the activity of NF-κB. Albumin enhanced the expression of Akt. Ly294002 inhibited albumin-induced the expression of NF-κB and partially decreased the level of MCP-1. Apositive correlation was noted between NF-κB activation and MCP-1 expression( r = 0.68 ,P ＜ 0.01 ). Conclusions Albumin-induces MCP-1 and NF-κB production via Akt signal pathway in renal tubular epithelial cells.
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Objective To explore the expression and significance of nestin in renal tubular epithelial cells in hypercholesterolemic rats. Methods Dietary-induced hyperlipidemia were induced in female SD rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, serum creatinine and renal interstitial pathological changes were assessed. The expression of nestin and a-smooth muscle actin (α-SMA) were detected by immunohistochemical stain. Results The serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine were significantly increased in hyperlipidemia group, accompanied with renal interstitial injury and fibrosis. As time extended, the expression of nestin and a-SMA in renal tubular epithelial cells were increased significantly. There was positive correlation among the expression of nestin and total cholesterol, low density lipoprotein, urinary albumin and serum creatinine( r =0.963,0.830,0.944,0.706, P <0.01). Nestin also had a positive correlation with tubular-interstitial index ( r = 0. 974, P < 0. 01) and α-SMA ( r = 0. 804, P < 0. 01). Conclusion The increased expression of nestin may be associated with renal tubular-interstitial fibrosis and tubular epithelial myofibroblast transdifferentiation in hypercholesterolemic rats.
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Objective To investigate the efficacy and safety of leflunomide as induction and mainten-ance therapy for class Ⅴ lupus nephritis. Methods Sixteen patients with lupus nephritis (of which, three proven with Ⅴ +Ⅲ, six with Ⅴ+Ⅳ ), proven by renal biopsies, were included in this study. ALL patients rec-eived LEF plus prednisone treatment. For induction therapy, all patients were given an initial loading dose of LEF 60 mg daily for three days, followed by 20 mg daily for the whole induction treatment period. Prednisone was given starting from 0.8 mg per kilogram daily, then tapered four weeks later. After twenty-four weeks, the dosages of LEF and prednisone were 10 mg/d, 5～10 mg/d respectively during maintenance therapy. We asses-sed total remission rates in the end of twenty-four weeks, as well as the changes of system lupus erythematosus disease activity index (SLEDAI), urinary protein per twenty-four hours (24 h Upr), serum albumin, serum creatinine level, complement C3, complement C4, C reactive protein, serum titer of ANA and anti-dsDNA be-fore treatment, 12 weeks, 24 weeks and 48 weeks after treatment respectively. Meanwhile, seven patients received repeated renal biopsies after completing induction therapy, so we compared pathological activity index (AI) and chroniciry index (CI) between pre-therapy and post-therapy at the same time. T and t' test were selected. Results Sixteen patients were followed-up. After 24 weeks induction therapy, the total remission rate was 75.0%; SLEDAI was significantly lower than pre-therapy [(15.4±3.5) vs (6.9±1.7), P<0.05]; 24 h Upr was also significantly lower than pre-therapy [(5.8±2.2) g vs (l.3±0.5) g, P<0.01 ]. Unfortunately, all seven patients performed repeated renal biopsies with class Ⅴ lupus nephritis again histologically, of which two were transformed other cater-ofies. Comparing with that of pre-therapy, AI was improved after therapy [(2.4±0.9) vs (1.7±0.8), P<0.05]. However, CI indicated no difference. Adverse events including major infection occurred in four patients. The adverse events happened at the 12 th week after treatment. Conclusion The efficacy of LEF plus corticoster-oids as induction and maintenance therapy for class Ⅴ lupus nephritis is remarkable and the tolerance of patients is good.
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Objective To evaluate the proteetive effect of Valerian oil on lipid-induced nephropathy in Hypercholosterolemic rats and study its possible mechanisms.Methods SD rats were randomly divided into control group,hyperlipidemia group,low-dose[12.5mg/(kg·d)]valerian oil group,middle-dose[25mg/(kg·d)]valerian oil group,high-dose[(50me/(kg·d)]valerian 0il group and simvastatin group[5ms/(kg·d)for lavage].Dietary-induced hyperlipidemia were by given 4％cholosteml and 1％cholic acid diet for 16 weeks.Changes of serum lipid,urinary albumin,renal function and renal pathobiology index were assessed.The expression of integrin α3β1in glomeruli was detected by immunohistochemical stain,the expression of integrin ot3～l and TGF-β1 mRNA were detected by RT-PCR at the same time.Results The serum levels of total cholesterol,low density lipopmtein and seruln creatinine in Valerian group and simvastatin group were decreased more than that in hypedipidemia group.Urinary albumin excretion Was significantly reduced。in Valerian group after treatment for 8 weeks,and significantly reduced in simvaatatin group after 16 weeks.The morphological analysis revealed that the pathobiology index in Valerian group were significantly decreased than that in simvastatin group after 16 weeks.At the sanle time,the expression of integrin α3β1 mRNA and protein in Valerian group were significantly increased than that in hyperlipidemia group and simvastatin group,and the expression of TGF-β1mRNA were markedly decreased in Valerian group.The treatment effect in Valerian group Wag better than that insimvaatatin group.Conclusion Valerian oil has the protective effects on lipid-induced nephropathy by decreasing serum lipid,increasing the expression of integrin α3β1 and inhibiting the expression of TGF-β1.The protective effects of Valerian oil ale better than simvastatin.
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The clinical data and routine biochemical parameters of 64 maintenance hemodialysis (MHD)patients and 20 controls were analyzed in the study.Serum cystatin C levels were detected by latex particle enhalice inununo-turbidimetry:and the cardial structure and function were assessed by echocardiography.As MHD time extended,the levels of semm cystatin C increased gradually,accompanied with high incidence of left ventricular hypertrophy(LVH).The LVH-positive patients had higher systolic blood pressure and left veHtricular mass index,and had higher serum cystatin C than tllose in LVH-negative patients.The serum cystatin C levels were positively correlated with left yentricular mass index(r=0.633,P<0.01)and systolic blood pressure(r:0.397,P<0.01).The results suggest that serum cystatin levels may be an influencing factor for long-term cardiacvascular complication in MHD patients.
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Objective Posterior reversible encephalopathy syndrome (PRES) is a rapidly evolving neurologic syndrome with characteristic clinical and radiographic features. To define the clinical characteristics of PRES in patients with eoneomitant systemic lupus erythematosus (SLE) by analyzing their clinical manif-estations and reviewing the literature. Methods The details of 4 cases and a review of the literature relevant to the development of PRES in association with SLE are presented. We described the clinical and imaging characteristics and associated risk factors of posterior roversible PRES in patients with SLE. Results Inclu-ding our cases, we reviewed a total of 48 patients with SLE and PRES. Hypertension was observed in 42 cases (88%), renal failure in 30 cases (63%), 39 recent onset cases were treated with immunosuppressive drugs and/or steroids recently (81%). Headache was observed in 46 cases (96%), Corffusion/coma in 20 cases (42%), seizures in 43 cases (90%), visual disturbances in 28 cases (58%). Neuroimaging demonstrated posterior white matter edema involving the parietal-occipital, temporal, frontal lobes, and cerebellum. The hypertension and other worsening factors should be treated. Conclusion PRES is a central nervous system syndrome that is observed in SLE patients. It is associated mainly to acute hypertension, renal failure, and immunosuppressive drugs. Although reversibility is common, residual neurological damage may be observed. Complete clinical and radiographic recovery oeeurrs with prompt antihypertensive treatment and supportive care.