Effects of sodium hydrosulfide on cardiac function and activity of renin-angiotensin-aldosterone system in rats with chronic heart failure / 中国病理生理杂志

AIM:To investigate the effect of sodium hydrosulfide(NaHS)on cardiac function and activity of renin-angiotensin(Ang)-aldosterone(ALD)system(RAAS)in the rats with chronic heart failure(CHF).METHODS:The CHF rat model was established by abdominal aortic coarctation.SD rats were randomly divided into sham operation group,model group,low dose of NaHS group and high dose of NaHS group(n=6).The left ventricular end-diastolic di-ameter(LVEDD), left ventricular end-systolic diameter(LVESD)and left ventricular ejection fraction(LVEF)were measured before and after treatment by echocardiography in each group.The levels of renin,AngⅡand ALD in the plasma were measured by ELISA.The expression of angiotensin-converting enzyme(ACE)and angiotensin Ⅱ type 1 receptor (AT1R)at mRNA and protein levels in the myocardium tissues was determined by qPCR and Western blot,respectively. RESULTS:After treatment with NaHS,compared with model group and before treatment,LVEDD and LVESD in low dose of NaHS group and high dose of NaHS group were decreased significantly, while LVEF was increased significantly(P<0.05).Compared with low dose of NaHS group,LVEDD and LVESD were decreased,while LVEF was increased in high dose of NaHS group(P<0.05).Compared with sham operation group,the levels of renin,AngⅡand ALD in the plasma of model group were significantly increased(P<0.05),and the expression of ACE and AT1R at mRNA and protein levels in the myocardium tissues of model group were significantly increased(P<0.05).Compared with model group,the plas-ma levels of renin,AngⅡand ALD in low dose of NaHS group and high dose of NaHS group were significantly decreased (P<0.05),and the myocardial expression of ACE and AT 1R at mRNA and protein levels was significantly down-regulated (P<0.05).The plasma levels of renin,AngⅡand ALD,and the myocardial expression of ACE and AT 1R at mRNA and protein levels in high dose of NaHS group were significantly lower than those in low dose of NaHS group(P<0.05). CONCLUSION:NaHS inhibits the activation of RAAS,thus improving the cardiac function of CHF rats,and the effect of high-dose NaHS is better than that of low-dose NaHS.

Effect of p27 gene combined with Pientzehuang (characters: see text) on tumor growth in osteosarcoma-bearing nude mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice.</p><p><b>METHODS</b>Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot.</p><p><b>RESULTS</b>The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05).</p><p><b>CONCLUSION</b>p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.</p>

Single nucleotide polymorphisms of the IL28B and sustained virologic response of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy: a meta-analysis

Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus [HCV] infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes. To assess the associations of single nucleotide polymorphisms [SNP] of the IL28B and sustained virologic response [SVR] of patients with chronic hepatitis C to PEG-interferon/ ribavirin therapy. We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate of SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied. The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans [OR =3.85, 95% CI:3.06-4.83]; the percentage of rs12979860 TT genotype was lower in Caucasians than that of Afro-Americans [OR=3.45, 95% CI=2.68-4.44]. Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 [OR=0.16, 95%CI: 0.11-0.24]. IL28B is significantly associated with response of PEG-interferon/ ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes

Renoprotective effect of adiponectin through an antioxidant mechanism in streptozotocin- induced diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the renoprotective effect of adiponectin in streptozotocin (STz)-induced diabetic rats and explore its association with oxidation stress.</p><p><b>METHODS</b>Type 2 diabetes mellitus was induced in rats by high-lipids and high-sucrose feeding and intraperitoneal STZ injection. The recombinant plasmid pIRES2-EGFP-gAd expressing globular adiponectin was intraperitoneally injected in the rats mediated by liposome. Thirty-two Wistar rats were randomized into 4 groups, namely the normal control group (NC), diabetic group without any therapy (DM), diabetic group treated with pIRES2-EGFP-gAd (DA) and diabetic group treated with pIRES2-EGFP (DP). After the corresponding treatments for 8 weeks, the blood glucose, HbA1c and urine albumin excretion rate (UAER) were measured, and the kidneys were collected to determine the production of reactive oxygen species (ROS) and assess renal pathologies. Immunohistochemistry and Western blot were employed to determine the protein levels of endothelial nitric oxide synthesis (eNOS) and phosphorylated AMP-activated protein kinase (pAMPK).</p><p><b>RESULTS</b>UAER and ROS production increased significantly in DM group as compared with that in the control group (P<0.05), while no significant differences were found in UARE among the DM, DA, and DP groups (P>0.05). Blood glucose level, HbA1c and ROS were significantly decreased in DA group in comparison with those in DM group (P<0.05). Glomerular hypetrophy, mesangial expansion, basal membrane thickening, tubular epithelial cells cavitation and exfoliation, and mononuclear lymphocyte infiltration occurred in DM group, while these changes were ameliorated in gAd transfection group. The renal expression levels of eNOS and p-AMPK proteins in DM group were significantly lower than those in the control group (P<0.05) and gAd transfection group (P<0.05).</p><p><b>CONCLUSIONS</b>The renoprotective effect of adiponectin may be at least partially mediated by the activation of the AMPK signaling passway, ROS production inhibition, relief of the oxidative stress, and up-regulation of eNOS expression in the renal tissue of diabetic rats.</p>

Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of vascular endothelial growth factor and connective tissue growth factor in cultured human peritoneal mesothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor beta1 (TGF-beta1) plays a key role in regulating tissue repair and remodelling after injury. Connective tissue growth factor (CTGF), a downstream mediator of TGF-beta1 inducing fibrosis, has been implicated in peritoneal fibrosis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis that can hasten peritoneal fibrosis. In this study, we investigated the effect of small interfering RNA (siRNA) of CTGF by pRETRO-SUPER (PRS) retrovirus vector on the expression of CTGF and VEGF in human peritoneal mesothelial cells.</p><p><b>METHODS</b>Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect human peritoneal mesothelial cell (HPMC). The cells were divided into seven groups: low glucose DMEM, low glucose DMEM + TGF-beta1 5 ng/ml, low glucose DMEM + TGF-beta1 5 ng/ml + PRS-CTGF-siRNA(1-4) and low glucose DMEM + TGF-beta1 5 ng/ml + PRS. The expression of CTGF and VEGF were measured by semiquantitative RT-PCR and Western blot.</p><p><b>RESULTS</b>Low levels of CTGF and VEGF were detected in confluent HPMCs. Following stimulation with TGF-beta1, the levels of CTGF and VEGF were significantly upregulated (P < 0.01). Introduction of PRS-CTGF-siRNA(1-4) resulted in the significant reduction of CTGF mRNA and protein, and VEGF mRNA (P < 0.01), especially in groups PRS-CTGF-siRNA1 and PRS-CTGF-siRNA4. The introduction of PRS void vector did not have these effects (P > 0.05).</p><p><b>CONCLUSIONS</b>The expression of CTGF siRNA mediated by PRS retrovirus vector can effectively reduce the level of CTGF and VEGF induced by TGF-beta1 in cultured HPMCs. This study may provide potential therapeutic strategies to prevent the peritoneal fibrosis.</p>

Inhibitive effect of troglitazone on TGF-beta(1) and fibronectin expression in human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of the peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist troglitazone on TGF-beta(1) and fibronectin (Fn) expression in human peritoneal mesothelial cells (HPMCs).@*METHODS@#HPMCs were cultured from human omentum by an enzyme digestion method, growing in medium containing 30 mmol/L D-glucose. TGF-beta(1) and Fn expression were measured in HPMCs in the presence and absence of 15 micromol/L troglitazone. The mRNA expressions of PPAR-gamma,TGF-beta(1) and Fn were determined by semi-quantification reverse transcriptive PCR (RT-PCR). The protein of TGF-beta(1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of PPAR-gamma and Fn were determined by Western blot.@*RESULTS@#The mRNA and protein expression of TGF-beta(1) and Fn were significantly increased in HPMCs stimulated with 30 mmol/L D-glucose compared with the control group with F12 media (P<0.01). Obvious decrease of TGF-beta(1) was found in troglitazone(15 micromol/L) treated group compared with group stimulated with 30 mmol/L D-glucose (P<0.05). Exposure of HPMCs to troglitazone reduced the Fn secretion (P<0.05).@*CONCLUSION@#Troglitazone reduced the expression of TGF-beta(1) in HPMCs stimulated by 30mmol/L D-glucose, and reduced Fn production. PPAR-gamma agonists may have a specific role in ameliorating the course of progressive peritoneal fibrosis under long-term peritoneal dialysis states.

Nephrotoxicity of high- and low-osmolar contrast media: Protective role of fosinopril or telmisartan in a rat model / 中南大学学报(医学版)

OBJECTIVE@#To compare the nephrotoxicity of high- and low-osmolar contrast media (HOCM and LOCM), and to determine the protective role of fosinopril or telmisartan and its possible mechanism.@*METHODS@#Forty eight healthy SD rats were randomly divided into 6 groups: a normal control group, a glycerol control group, a low-osmolar contrast media (LOCM) group, a high-osmolar contrast media (HOCM) group, a fosinopril group, and a telmisartan group. Glycerine for inducing kidney damage was given to all rats except the normal control group. Twenty-four hours after the injection of glycerine, the mixed fosinopril suspension (10mg/kg) or telmisartan (5mg/kg) was poured into the stomach in the preventive group. Serum creatinine (SCr) and plasma angiotensin II (AngII) levels were detected by an automatical biochemical analyzer and radioimmunoassay; caspase-3 activity and claudin-1 expression of the renal tissue were detected by fluorometric method and immunohistochemical method. The renal injury was assessed by hematoxylin and eosin (HE) staining and terminal deoxynucleotide mediated nick and labeling (TUNEL) staining, respectively.@*RESULTS@#In diatrizoate-injected rats, SCr and AngII levels were increased (P<0.05). Expression of claudin-1 protein and caspase-3 activity in the renal tissue was upregulated. The histologic changes and percentage of apoptotic cells were milder in the LOCM rats than those in the HOCM rats. In the group pretreated with fosinopril or telmisartan, no increase in the levels of SCr and AngII was discovered. The expression of claudin-1 protein and caspase-3 activity was significantly lower than that in the HOCM group. The renal injuries induced by diatrizoate were alleviated.@*CONCLUSION@#Both HOCM and LOCM could cause cellular apoptosis in the kidney.LOCM was less toxic to rat kidney than HOCM. Nephrotoxicity induced by HOCM might be related to caspase-3, claudin-1 and AngII. Fosinopril or telmisartan may protect the renal tissue from nephrotoxicity induced by diatrizoate.

Effects of high glucose on the cell proliferation, damage and cytokine in human peritoneal mesothelial cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.@*METHODS@#The third passage human peritoneal mesothelial cells (HPMCs) from primary culture were divided into a control group (F(12)) and high glucose groups (F(12)+4% glucose) in different times (24, 48 h). The cell proliferation was assayed by the method of MTT (methylthiazoletetrazolium). The cell damage was measured by LDH (lactate dehydrogenase). The protein expression of fibronectin (FN), transforming growth factor-beta1(TGF-beta(1)) and connective tissue growth factor (CTGF) were detected by ELISA. The mRNA expression of FN, TGF-beta(1) and PAI-1 were detected by RT-PCR.@*RESULTS@#High glucose suppressed the cell proliferation. The result of MTT showed that compared with the control group, the value of OD of high glucose groups at 24 or 48 h decreased significantly (P<0.01 or 0.01); The cell damage was enhanced in high glucose groups, at 24 or 48 h compared with the control group at the same time (all P<0.01). The protein expressions of TGF-beta(1), CTGF and FN in supernate fluid of cell culture were significantly enhanced when high glucose stimulated the HPMCs in the high glucose groups at 24 or 48 h compared with the control group at the same time (P<0.05 or 0.001). The expressions of FN, TGF-beta(1) and PAI-1 mRNA were upregulated in 24 h high glucose group compared with that of 24 h control group.@*CONCLUSION@#High glucose can suppress the HPMC proliferation and damage HPMCs. Increase of TGF-beta(1), CTGF, FN and PAI-1 of HPMCs stimulated by high glucose can promote the synthesis and decreased degradation of extracellular matrix, which might be related with the mechanism of peritoneal fibrosis of peritoneal mesothelial cells by high glucose.

Comparision of several different peritoneal fibrosis rat models / 中南大学学报(医学版)

OBJECTIVE@#To compare different types of peritoneal fibrosis models in rats.@*METHODS@#Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose + lipopolysaceharides (LPS) group (4.25% PDF + LPS, Group 4), high glucose + erythromycin group (4.25% PDF + lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/ Purea), glucose reabsorption (D2/D0), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy.@*RESULTS@#The D2/D0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 (P < 0.05) . The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0. 05 ). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0.05 ).@*CONCLUSION@#Different types of peritoneal fibrosis models in rats has been established. The best model is high clusion glucose + erythromycin.