ABSTRACT
Objective Determining the respective incidence, risk factors and prognosis of hyperuricemia post normothermic cardiac surgery with cardiopulmonary bypass. Methods Clinical data was collected from April 2002 to October 2004. 232 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients were classified into three groups: nonhyperuricemia group, hyperuricemia group, and acute goutynephropathy group. Uricemia levels 24 hours post cardiac surgery, the respective incidence, risk factors, and prognosis among three groups were analyzed. Results Seventy patients (30.1%) had hyperuricemia, and twenty-two patients (9.5%) had acute goutynephropathy during their ICU stay. The mortality was 0.7% for no hyperuricemia group, 1.4% for hyperuricemia group, and 13.6% for acute goutynephropathy group (P
ABSTRACT
Objective To study the protective effects of tripterine on experimental lupus nephritis glomerulosclerosis.Methods Different doses of tripterine were injected peritoneally to BW F1 mice at different stages.The levels of 24 hour urine protein excretion and serum anti dsDNA antibodies,and the expressions of renal collagen type Ⅰ,type Ⅳ,MMP 2,TIMP 2,and transforming growth factor (TGF) ? 1 mRNA were analyzed.Results ①Tripterine suppressed the development of proteinuria,decreased the level of serum anti dsDNA antibodies,reduced the local expressions of TGF ? 1,collagen type Ⅰ,type Ⅳ,TIMP 2 and improved the expression of MMP 2 in murine kidney.②The use of tripterine before occurence of proteinuria got more obvious protective effects than it did after the occurence of proteinuria.③No significance was found between both 3 mg/kg (a week) tripterine treated and 6 mg/kg (a week) groups.Conclusion Tripterine has a definite protective effect on glomerulosclerosis of the lupus murine model.The decrease of renal collagen type Ⅰ and type Ⅳ is probably due to its suppressive effects on the expression of local TGF ? 1,TIMP 2 and its improvement effect on the local expression of MMP 2.
ABSTRACT
Purpose To study the effects of α-tocopherol on activator protein-1(AP-1)binding and TGF-β1 expression induced by high glucose in rat mesangial cells and further to clarify the molecular mechanism of antioxidant in treating diabetic nephropathy. Methods AP-1 binding of the rat mesangial cells exposed to high glucose was detected by gel shift assay.The Jun,Fos compositions of AP-1 dimer were determined by supershift assay.Protein expression of TGF-β1 was detected by Western blot.Additionally,the effects of α-tocopherol on AP-1 binding and TGF-β1 expression induced by glucose in rat mesangial cells were also studied. Results High glucose stimulated AP-1 binding of mesangial cells in time-and-dose-dependent manners .This AP-1 binding increase involved JunD and Fos as shown by gel supershift.Glucose also increased protein expression of TGF-β1 at same time.The increased AP-1 binding and TGF-β1 were inhibited with pretreatment with α-tocopherol in glucose-treated mesangial cells. Conclusions This study suggests that α-tocopherol can significantly inhibit AP-1 activity and TGF-β1 expression by glucose in rat mesangial cells,which may be one of its antioxidation mechanisms to retard diabetic nephropathy.
ABSTRACT
Objective To explore the possible mechanism of nitric oxide(NO) involved in iron-mediated cytotoxicity on renal tubular cells, meanwhile to estimate the effect of reactive oxygen sepcies scavenger on iron-mediated cytotoxicity and its relation to nitric oxide. Methods in this study, the relationship between NO production and lactate dehydrogenase(LDH) release were observed in primary subconfluent proximal tubular cells coincubated with different doses of NTA-Fe and lipopolysaccharide(LPS) alone or in combination. NO production was monitored by NO2 -- concentration in supernatant based on Griess reaction. Meanwhile, semi-quantitative RT-PCR was applied to detect the inducible nitric oxide synthase (iNOS) mRNA level induced by NTA-Fe and LPS together. In addition, experimental groups were exposed to reactive oxygen species (ROS) scavengers to determine the impact of the interaction between NO and ROS on iron-mediated cytotoxicity. Results After 12-hour coincubation, NTA-Fe could increase both LDH release and NO2 production in a dose-dependent manner (P 0. 05 ) although tubular injury was aggravated (P
ABSTRACT
Objective To study the effects of insulin resistance on the occurance of hypertension in uremia. Methods With use of the oral glucose tolerance test (OGTT) and the insulin release test (IRT) , insulin glycoregulatory activity, including insulin sensitivity index (ISI) , glucose uptake rate (M) and the total areas under the glucose and insulin curves during OGTTs (AUCG, AUCINS) were investigated in 29 hypertensive (CRF-H) and 21 normotensive (CRF-NH) urernic patients and 12 healthy controls (C), and their plasma renin activity (PRA), angiotensin Ⅱ (AT Ⅱ) levels were investigated too. Results (1) Uremic patients had significantly higher blood glucose and serum insulin levels after glucose load, much higher AUCG and AUCINS values and significantly lower ISI and M values than the controls, compared with the CRF-NH patients, CRF-H patients had significantly higher blood glucose levels at 30', 60', 120', and higher serum insulin levels at 120' during OGTTS, significantly higher AUCG and AUCINS values, significantly lower ISI and M values and significantly increased incidences of insulin resistance and glucose intolerance; (2) Insulin resistant patients had more frequency and severe hypertension than the non-insulin resistant ones; simple regression showed that arterial blood pressure (SBP, DBF, MBP) had significant negative correlation with ISI and M, significant positive correlation with AUCG and AUCINS; (3) The levels of PRA, ATⅡbetween two CRT groups were not different; (4) Multiple linear regression showed that AUCG and AUCINS had significant positive correlation with MBP independent of age、 sex、 obesity、 the degree of real failure and plasma renin-angiotensin activity. Conclusion Insulin resistance 、 hyperinsulinemia and glucose intolerance or hyperglycemia may be one of the important mechanisms of uremic hypertension.
ABSTRACT
Objective To investigate the possible role of protein kinase(PK) activity in the induction of AP-1 by ox-LDL in mesangial cells and to elucidate the upstream signal pathways involved in the ox-LDL-induced AP-1 binding. Methods Rat mesangial cells were randomly divided into the normal cells, ox-LDL-treated cells and PK inhibitor + ox-LDL-treated cells. Treatments with the PKC inhibitor bisindolylmaleimide I, the PKA inhibitor H89, the PTK inhibitor genistein (GEN), the MEKi inhibitor PD98059, or the p38 MAPK inhibitor SB203580 were applied prior to a 24-hour incubation of ox-LDL in mesangial cells. The phosphorylation of MAPK families was detected by Weatern blot analysis. AP-1 binding was determined by gel shift assay. Results Ox-LDL stimulated the phosphorylation of JNKi/SAPK and p38 MAPK( P 0. 05) . Bisindolylmaleimide I at 50, 100, 200 nmol/L appreciably reduced the ox-LDL-induced AP-1 binding. H89 at 0. 5, 5 umol/L significantly inhibited AP-1 binding by ox-LDL. GEN at 25, 50 umol/L did not reduce the AP-1 binding by ox-LDL, but when GEN rose up to 100 umol/L, the ox-LDL-induced AP-1 binding significantly decreased in mesangial cells. However, SB203580 and PD98059 did not reduce the ox-LDL-induced AP-1 binding in the present study. Conclusion Multiple protein kinases may involve in the stimulation of AP-1 by ox-LDL in mesangial cells.