Research on preventative role of Nrf2 in kidney diseases / 中国药理学通报

Nrf2,a key transcriptional factor in regulating endog-enous antioxidant signaling pathway,maintains the redox bal-ance by controlling the expression of a battery of antioxidant en-zymes,phase-Ⅱ detoxification enzymes and phase-Ⅲ transport-ers.Furthermore,Nrf2 regulates inflammation.Recent resear-ches have confirmed that Nrf2 provides a vital physiological role in kidney diseases,activation of Nrf2 enhances the antioxidant and anti-inflammatory ability in cellular and tissue levels,thusalleviates renal injury.Here,this article aims to summarize the protective effect of Nrf2 on various models of kidney impairment and explore the potential of Nrf2 as a therapeutic target to pre-vent kidney diseases.

The influence of mutagenic lactobacilli on concentration of indoxyl sulfate in blood and the renal expression of renal fibrosis-related factors / 中国医师杂志

Objective To investigate the concentration change of indoxyl sulfate (IS) in blood and the renal expression of renal fibrosis-related factors (transforming growth factor-beta 1, TGF-β1;fibronectin, FN) after administration of mutagenic lactobacilli by oral.Methods A total of 60 male Sprague-Dawley (SD) rats aged 6 weeks was divided randomly into 3 groups.The normal control group (Sham group, n =20) received Sham operation of just incision of skin without kidney removed.The other two groups of rats were renal failure models selected from survivals of the other 40 rats who received real operation with 5/6 of kidney removed.Finally, 35 survived renal-failure rats were divided randomly into 2 groups : pathological control group(Model group, n =17) who were administrated of 2ml sterile saline solution once a day by gavage, and experimental group (lactobacillus bulgaricus (LB) group, n =18) who were administrated of 2 ml mutagenic lactobacilli (1.5 × 108 cfu/ml) once a day by gavage.Eight weeks later, blood specimens were taken to test the concentration of IS with high performance liquid chromatography-fluorescence detection (HPLC-FLU), and urea and creatinine by automatic biochemical analyzer;moreover, the rats were killed to get kidney tissues for pathological examination.Results The levels of serum IS, urea, and creatinine were statistically significantly different between two groups (P ＜ 0.05).Both the levels of renal tubular damage and renal interstitial fibrosis were both lessen in the experimental group compared to the model group (P ＜0.05).TGF-β1 and FN expressions in renal tissues were significantly decreased (P ＜0.05).Conclusions Mutagenic lactobacilli not only reduces serum concentration of IS, urea and creatinine in renal failure rats but lowers the expressions of TGF-β1 and FN in renal tissues.

Comparison of the expressions of vascular endothelial growth factor and microvessel density in small intestine mucous membrane with urea and creatinine elimination in renal failure rat used Shenfushu and atropine treatment / 中国医师杂志

Objective To investigate the relationship between that vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) distribution were in the small intestine mucous membrane and that urea and creatinine were eliminated from intestine inrenal failure rat used Shenfushu and atropine treatment.Methods Sprague-Dawely (SD) rats with 5/6 kidney resection were randomly divided into Shenfushu treatment group,Shenfushu + atropine treatment group,pathological control group,and sham operation group for the normal controls.Treatment groups were drenched for eight weeks.Before and after treatment,the concentration of blood urea nitrogen (BUN),serum creatinine (Scr),the fecal urea and fecal creatinine were detected; the expression levels of VEGF and MVD in the small intestinal were detected with small intestinal biopsy immunohistochemical method.The relationship between that expression of VEGF and MVD,and that concentration of BUN,Scr,the fecal urea,and fecal creatinine was analyzed.Results VEGF in the Shenfushu treatment group,Shenfushu + atropine treatment group,and pathological control group was (20.72 ± 1.8) pu,(24.32 ± 1.54) pu,and (28.69 ± 1.82) pu,respectively; MVD was (274.27 ± 10.62)/mm2,(332.71 ± 10.96)/mm2,(436.42 ± 13.70)/mm2,respectively.Expressions of small intestinal VEGF and MVD in two treatment groups were increased significantly than the control group.The concentrations of BUN and Scr were significantly decreased with a negative correlation with the expressions of VEGF and MVD.The concentrations of fecal urea nitrogen and fecal creatinine were significantly increased with a positive correlation with the expressions of VEGF and MVD (P ＜0.05).The concentrations of BUN and serum Cr in the Shenfushu + atropine group were significantly changed more than Shenfushu group (P ＜ 0.05).Conclusions Shenshuaikang and atropine could enhance the expression of VEGF in the small intestinal mucosa,increase microvascular density,promote the elimination of urea nitrogen and creatinine from the intestinal tract to decrease the concentrations of BUN and Scr.Those effects were more obvious with two drugs in combination.

Investigation of enterotoxin gene in clinical isolates of Staphylococcus aureus / 南方医科大学学报

<p><b>OBJECTIVE</b>To detect the enterotoxin genes of Staphylococcus aureus (SA) isolated from clinical specimens and analyze the correlation between enterotoxin genes and drug resistance of SA.</p><p><b>METHODS</b>The mecA gene and enterotoxin genes A-F of clinical SA isolates were identified by polymerase chain reaction (PCR), and the genes were sequenced to investigate the correlation of these genes to drug resistance.</p><p><b>RESULTS</b>The detection rate of enterotoxin genes was 100% in 67 methicillin- resistant SA (MRSA), showing no significant difference from the rate in 57 methicillin-sensitive SA (MSSA) (83.5%, χ(2)=0.203, P>0.05). Of the 116 strains carrying enterotoxin genes (93.5%), the detection rates of SEA, SEB, SEC, SED and SEF were 90.5%, 6.9%, 61.3%, 5.2%, 25.9% and 93.5%, respectively, and none of the strains were positive for SEE gene. In these strains, 78 (67.2%) carried 2 or more enterotoxin genes, and the main genotypes were SEA and SEC (33.6%), SEA and SEF (7.8%), and SEA and SEC and SEF (13.8%). Compared with the strains carrying a single enterotoxin gene, those with multiple enterotoxin genes showed a higher drug resistance rate, among which 75% of the SA strains carrying SEA+SEC+SEF were resistant to SXT, significantly higher than the rates of SA carrying SEA (28.6%) and SEA+SEC (38.7%) (P<0.05). The SA strains carrying SEA+SEC+SEF and SEA+SEF showed significantly higher amikacin resistance rates than SA strain carrying SEA (75.0%, 77.0%, 21.5%, respectively, P<0.05).</p><p><b>CONCLUSION</b>Clinical isolates of SA carrying multiple enterotoxin genes have a higher drug resistance rate than those with a single enterotoxin gene, suggesting the the important role of enterotoxin in multidrug resistance.</p>

The study of cytotoxic effect to creatinine metabolite on HK-2 cells in vitro / 中国医师杂志

Objective To investigate the effect of methylguanidine and 1-methylhydantoin on cells cytotoxicity, apoptosis in human renal tubular epithelial cell line (HK-2). Methods Human PTEC cell line HK-2 was used in this study. HK-2 was cultured and divided into 3 groups: Norma1 control group (A), methylguanidine group(B) and 1-methylhydantoin group (C). The cell inhibitory rate of HK-2 was detected by MTT method. The cytotoxicity of methylguanidine to HK-2 was determined by NAG release test. Cell apoptosis was evaluated by using Hoechst stain and FACS with Annexin-V/PI. Results The OD value and NAG concentration of creatinine, methylguanidine and 1-methylhydantoin group were compared with normal control group. OD value decreased and NAG concentration significantly increased(0.188±0.011, 0.176±0.010 vs 0.545±0.021, F＝1557.74, P＜0.01; 20.488±0.473, 22.225±0.565 vs 5.125±0.198, F＝3848.22, P＜0.01). By Hoechst stain, pycnosis and apoptotic body could be found when HK-2 was cultivated in methylguanidine 1-methylhydantoin group. In methylguanidine, 1-methylhydantoin group apoptotic HK-2 apparently increased, compared with that in control group (18.23±1.1581, 20.22±1.1433 vs 2.473±0.321, F＝526.06, P＜0.01). Compared with group B, the OD value in group C decreased significantly (0.176±0.010 vs 0.188±0.011,t＝2.26, P＜0.05), NAG concentration increased significantly (22.225±0.565 vs 20.488±0.473,t＝-6.67, P＜0.01), and apoptotic rate in-creased significantly (20.22±1.1433 vs 18.23±1.1581,t＝-2.762, P＜0.05). Conclusions 1-methylhydantoin has more powerful cytotoxic effect to renal tubular epithelial cells than that of Methylguanidine.

Field planting of Bacillus bifidus and Bacillus acidi lactic on various gastrointestinal sites and their decomposition of low molecule urotoxins in rats with renal failure / 中南大学学报(医学版)

OBJECTIVE@#To investigate the field planting of Bacillus bifidus and Bacillus acid lactic on mucosa membrane of gaster, jejunal, ileum, ascending colon, and descending colon in rats with renal failure, and to observe their decomposition of creatinine (Cr), urea nitrogen (UN),and uric acid (UA).@*METHODS@#Forty SD rats were randomly divided into 4 groups. Group A was normal control group,and 10 of them were sham-operated. Thirty of them were operated with 5/6 nephrectomy. Group B was pathological control group. Group C were fed Bacillus bifidus and Group D were fed lactobacillus. After 1 week all rats were sacrificed as samples of blood, digestive juice and gastrointestinal mucosa were taken.Bacteria on the gastrointestinal mucosa were counted. The concentration of UN, Cr,and UA of blood and digestive juice was determined.@*RESULTS@#The number of bacteria on the gastrointestinal mucosa of Group B was less than that of Group A (P<0.05), but that of Group C and D was more than that of Group A and B. The bacteria number on the gastric mucosa was least and that on the descending colon was most. There was significant difference in the bacteria number and concentration of Cr, UN,and UA in various sites of the gastrointestinal tract (P<0.05). The concentrations of Cr, UN, and UA in the digestive juice of various sites and serum in Group C and D were lower than those in Group B (P<0.05). Bacteria planting number in the digestive tract has obvious negative correlation with the concentration of Cr,UN, and UA in the blood and digestive tract.@*CONCLUSION@#Field planting of lactobacillns and Bacillus bifidus, and the concentration of low molecule urotoxin are different in various sites of the gastrointestinal tract. It can decrease the concentration of BUN,Cr,and UA in rats with renal failure by feeding lactobacillus and Bacillus bifidus.

Effects of celecoxib and Indomethacin on the VEGF and Microvessel Density in remnant kidney of rats with 5/6 subtotal nephrectomy / 中国医师杂志

Objective Our aim is to investigate the effects of lndomethacin on the expression of VEGF and the change of Micmves-sel Density(MVD)in remnant kidney of rats with 5/6 subtotal nephrectomy(STNx).Methods The renal subtotal ablation model was established by surgically 5/6 renal resection of the male Spragne-Dawley(SD)rats.Three groups were divided in our experimental protocol,including Sham,STNx and STNxI group.At the 8th week after gastric gavage,pathological changes of the remnant kidney were evaluated.Immunohistachemistry were used to examine the expression ofVEGF and MVD in the remnant kidney.Results At the 8th week after gastric gavage,only Up was significant decreased(P<0.05).TIS in Indomethacin group WaS significandy increased(P<0.05)and the preitu bular capillary density wa$significant decreased(P<0.05),compared with STNx group.Although BUN,Cr,the remnant kidney glomerulus's GSI were also decreased,the difference was not statistically significant(P>0.05).The glomendus～capillary density had no signifi-cant difference(P>0.05).In all rats,the expression of VEGF was positive correlated with capillary density between glomemlus and tubu-lointerstitimn(P<0.05).Conclusions Iadomethacin Can decrease UP in remnant kidney of rats with 5/6 subtotal nephrectemy(ST-Nx),and decrease the preitubular capillary density and aggravate mbulointerstitial injury at the same time.

Interleukin-1? up-regulates the expression of VEGF in A549 cell line / 基础医学与临床

Objective To investigate the regulation effect of interleukin-1? (IL-1?) on the expression of VEGF in A549 cells. Methods A549 cells were incubated with IL-1? in the presence or absence of Celecoxib. After incubation, cells were harvested to detect VEGF mRNA by reverse transcription-polymerase chain reaction (RT-PCR), and the supernatant was collected to determine the concentration of VEGF protein by enzyme-linked immunosorbent assay (ELISA). Results After treatment with IL-1?, the expression of VEGF mRNA and protein in A549 cells were significantly higher than that in the control group(P

Study on the Creatinine Utilization of Intestinal Bacteria in Patients with Uremia and Healthy Subjects / 中国医师杂志

Objective To explore the ability of intestinal bacteria making use of creatinine in the patients with uremia and healthy subjects. Methods Creatinine, which was energy source only,and tetrazolium violet as indicator were added into intestinal bacteria of the patients with uremia and healthy subjects(n=10). It was positive that solution showed violet. Intestinal bacteria were added in Nutrient Broth medium with creatinine. The concentration of creatinine was measured before and after incubation. Results The solution of intestinal bacteria of the patients with uremia showed violet. The solution of intestinal bacteria of healthy subjects showed bright violet.The concentration of creatinine decreased after incubation in both groups. Conclusions The intestinal bacteria of uremic patients and healthy subjects had the ability to make use of creatinine. The former was stronger than the latter.

Expression and Significance of HIF-1? in Non Small Cell Lung Cancer Tissues / 中国医师杂志

Objective To investigate the relationship between the HIF-1? expression and tumor biological characteristics in non small cell lung cancer(NSCLC). Methods The expression of HIF-1? in NSCLC tissues was evaluated by immunohistochemical method. Results The positive rate of HIF-1? expression in NSCLC was 71.11%, and significantly higher than that in normal lung tissues(P

Expressions of COX-2 and VEGF in non-small cell lung cancer and the relationships between them and tumor angiogenesis / 中国医师杂志

Objective To investigate the expressions of Cycloxygenase-2(COX-2),vascular endothelial growth factor(VEGF) in non-small cell lung cancer(NSCLC) to explore the relationships between them and the tumor biological characteristics,tumor angiogenesis in NSCLC.Methods The expressions of COX-2,VEGF and the microvessel density(MVD) were detected by immunohistochemical staining.Results The positive rates of COX-2 and VEGF expression in NSCLC tissue were 55.5% and 66.7% respectively,with significantly higher than those of normal lung tissue(all P