Objective To investigate the role of losartan in AT2-R mediated renal protective effects in renovascular hypertension rat. Methods Male SD rats were divided into sham group and renovascular hypertension group in which Goldblatt methods were performed. The two groups were intragastically administered with losartan (respectively 0, 10, 20, 30 mg?kg-1?d-1) for 6 weeks. Then renal function was measured, the AT2-R expression in the non-ischemic kidney and the AngⅡ contents in non-ischemic kidney and plasma were determined. Results In renovascular hypertension rats, especially in the contralateral, non-ischemic kidney, the expression of AT2-R protein were up-regulated. Losartan increased the AngⅡ contents in non-ischemic kidney and plasma, mediated the natriuretic/diuretic effect and renal protective effect in renovascular hypertension rat and increased the expression of renal AT2-R. Conclusion In renovascular hypertension rat, losartan mediates renal natriuretic/diuretic effect and protects renal function through up-regulating AT2-R in kidney.

OBJECTIVETo investigate the correlation of the autophagy-associated gene Atg5 with the pathogenesis of prostate cancer.

METHODSUsing real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry, we detected the expression of Atg5 in 50 cases of prostate intraepithelial neoplasm (PIN), 69 cases of prostate cancer (PCa), and 30 cases of benign prostatic hyperplasia (BPH).

RESULTSThe expression level of Atg5 mRNA was significantly higher in PIN (5.270 ± 0.230) and PCa (5.131 ± 0.252) than in the BPH tissue (1.723 ± 0.017) (P <0.01), and so was the positive rate of the Atg5 expression in the patients of the PIN group (94%) and PCa group (88.4%) than in those of the BPH group (6.7%) (P<0.01), but with no statistically significant differences between the PIN and PCa groups (P >0.05). No significant correlation was observed between the expression of Atg5 and the Gleason score of PCa (P >0.05).

CONCLUSIONThe upregulated expression of Atg5 might play a role in the tumorigenesis of prostate cancer.

Aged ; Autophagy ; Autophagy-Related Protein 5 ; Humans ; Immunohistochemistry ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Prostatic Hyperplasia ; genetics ; Prostatic Neoplasms ; genetics ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Up-Regulation

Objectives To observe the changes of the detrusor excitability and contractility and to study the mechanism of the unstable bladder. Methods Detrusor strips were obtained from prostectomy patients with benign prostatic hyperplasia. According to the results of urodynamic examination, patients were divided into detrusor instability (DI) and detrusor stability group(DS). Test of mechanical tension and stimulations with electricity and carbachol were performed on the excitability and contractility of the detrusor strips from 8 patients selected from each of the groups in vitro . Results The minimum tension of the detrusor strips when contraction occurred in DI and DS was (0 324?0 132)g and (0 822?0 216)g, respectively. There was significant difference between DI and DS ( P

Objective:To study the effects of pioglitazone on atherosclerosis on ApoE-/-mice,and to investigate the roles of adiponectin and its receptors.Methods:ApoE-/-mice were fed with high-fat chow for the induction of atherosclerosis and were divided into three subgroups:placebo(n=10),low-dose[10 mg/(kg?d),n=10] pioglitazone therapy,and high-dose[20 mg/(kg?d),n=10] pioglitazone therapy.C57BL/6J wild type mice(n=9) were used as control.Aortic atherosclerosis and intima-media thickness(intima-media thickness,IMT) of abdominal aorta were monitored,and plasma adiponectin was also measured.Expression levels of the adiponectin receptor 1(AdipoR1)and adiponectin receptor 2(AdipoR2) in vessels were analyzed(RT-PCR).Results:(1) Aortic atherosclerotic lesions were observed in ApoE-/-mice but not in wild type mice.Interestingly,these lesions were significantly prevented by high-dose pioglitazone therapy.Compared with wild type mice,ApoE-/-mice had increased IMT of abdominal aorta [(0.290?0.063 vs 0.178?0.012) cm,P

Effect of haemorrhagic shock on somatostatin (ss)-immunoreactive cells in rat pancreas was studied with the immunohistochemical PAP method. The results showed that at different time from 30 mins to 6 hours after haemorrhagic shock the number of SS-immunoreactive cells in pancreas was decreased significant. It is suggested that after haemorrhagic shock the releasing rate of somatostatin from the pancreatic D cells is increased. Therefore, the pancreatic D cells may play a role in the regulation of the pathological process of haemorrhagic shock.

Objective To study the inhibition of berberine on organ anion transporters (OATs) and its bidirectional trans-membrane transport.Method The transgene cell lines of the organ anion transporters including OAT1,OAT2,OAT3,OAT4,OAT7,and URAT1 were constructed and selected by animal cell transgenic method mediated by transporter Lipo 3000.Wild type (WT) cells were used as control group,and activity of OATs was verified by adding their radiolabeled substrates and inhibitors.The inhibition of 100 μmol/L berberine on the transporters was investigated in vitro.The IC50 of berberine on URAT1 was also determined.The bidirectional transport of berberine was studied through the Caco-2 model.Result The results showed that 100 μmol/L berberine inhibited the activity of OAT1,OAT2,OAT3,OAT4,OAT7 and URAT1 to (70.48±4.23)％,(69.13±1.28)％,(72.12±3.28)％,(79.77±6.49)％,(69.51 ±5.99)％ and (38.4 ± 2.67)％ respectively,the IC50 of berberine to URAT 1 was 13.19 μmol/L,the Papp (A-B) of 50 μmol/L and 100 μmol/L berberine were separately 0.28 × 10-6 and 0.40 × 10-6 cm/s,and the effiux rates were separately 3.18 and 3.15.Conclusion Berberine shows a stronger inhibition to URAT1 compared to OAT1,OAT2,OAT3,OAT4 and OAT7.Berberine may be the substrate of some effiux transporters.This study provides theoretical basis for explaining the low bioavailability ofberberine and forecasting the possible drug-drug interaction.

This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; chemistry ; pharmacology ; Cell Line ; Cyclooxygenase 2 ; immunology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavanones ; chemistry ; pharmacology ; Free Radical Scavengers ; chemistry ; pharmacology ; Ilex ; chemistry ; Interleukin-6 ; immunology ; Macrophages ; drug effects ; immunology ; Mice ; Nitric Oxide ; immunology ; Tumor Necrosis Factor-alpha ; immunology

0.05).Compared with the CSS,GMFM and WV before treatment,there were statistically difference after 6 and 12 weeks treatment in two groups(Pa

OBJECTIVETo study apoptosis induced by cadmium chloride (CdCl2) and the alteration in activity of protein kinase B (PKB/Akt) in adrenocortical cells.

METHODSFasciculata-glomerulosa (FG) cells of male guinea pigs were dispersed and primarily cultured in vitro. Features of apoptotic cells were observed using combined labeling with annexin-V and propidium iodide (PI) and flow cytometry. The activity of PKB/Akt was determined with immunoprecipitation and the chemiluminescence assay.

RESULTSApoptosis rate of FG cells increased with dose of CdCl2 two hours after treatment with 6.25-100.00 micromol/L of it, with significant difference in the groups treated with 25.00, 50.00, 100.00, micromol/L of CdCl2, as compared with the control group (P < 0.01). Regression analysis showed that occurrence of apoptosis correlated with the dose of CdCl2 in a dose-response pattern. In the meanwhile, there were obviously elevated percentages of apoptotic cells as the increase in duration of incubation ranging from 5.58% to 73.08% for incubating cells with 50.00 micromol/L of CdCl2, from 15 minutes to 4 hours. Duration of incubating cells with CdCl2 were correlated with occurrence of apoptosis in a time-effect manner. The gray scales of PKB/Akt were manifested to be decreased as the ascending of CdCl2 dosage from 6.25 to 200.00 micromol/L, with the linear correlation.

CONCLUSION6.25 to 100.00 micromol/L CdCl2 might elicit apoptosis of adrenocortical cells. Meanwhile, PKB/Akt is decreased.

Adrenal Cortex ; drug effects ; enzymology ; pathology ; Animals ; Apoptosis ; drug effects ; Cadmium Chloride ; toxicity ; Cells, Cultured ; Guinea Pigs ; Male ; Proto-Oncogene Proteins c-akt ; metabolism

This study was aimed to establish a stable animal model of left ventricular hypertrophy (LVH) to provide theoretical and experimental basis for understanding the development of LVH. The abdominal aorta of male Wistar rats (80-100 g) was constricted to a diameter of 0.55 mm between the branches of the celiac and anterior mesenteric arteries. Echocardiography using a linear phased array probe was performed as well as pathological examination and plasma B-type natriuretic peptide (BNP) measurement at 3, 4 and 6 weeks after abdominal aortic constriction (AAC). The results showed that the acute mortality rate (within 24 h) of this modified rat model was 8%. Animals who underwent AAC demonstrated significantly increased interventricular septal (IVS), LV posterior wall (LVPWd), LV mass index (LVMI), cross-sectional area (CSA) of myocytes, and perivascular fibrosis; the ejection fraction (EF), fractional shortening (FS), and cardiac output (CO) were consistently lower at each time point after AAC. Notably, differences in these parameters between AAC group and sham group were significant by 3 weeks and reached peaks at 4th week. Following AAC, the plasma BNP was gradually elevated compared with the sham group at 3rd and 6th week. It was concluded that this modified AAC model can develop LVH, both stably and safely, by week four post-surgery; echocardiography is able to assess changes in chamber dimensions and systolic properties accurately in rats with LVH.