ABSTRACT
Objective To investigate the effect of dietary zinc deficiency on the proliferation of esophageal epithelial cells in mice and related mechanism. Methods Twenty C57BL/6 mice were randomly divided into two groups and fed with zinc-sufficient diet and zinc-deficient diet respectively. We observed the changes of body weight, zinc concentration in blood and tissues, and the expression of PCNA, P38MAPK, NF-κB p105, NF-κB p65 and COX-2 proteins in the esophageal mucosa tissues. Results Compared with the zinc-sufficient group, the body weight and zinc content in blood and esophageal mucosa were significantly decreased in the zinc-deficient group (P < 0.05). Immunohistochemical results showed that PCNA, P38MAPK, NF-κB p105, NF-κB p65 and COX-2 in the esophageal mucosa of the zinc-deficient group were significantly increased. Conclusion Insufficient dietary zinc intake can inhibit the growth of mice and promote the proliferation of mouse esophageal epithelial squamous cells. The mechanism is related to the induced overexpression of COX-2, P38MAPK, PCNA, NF-κBp and other tumor-related factors.
ABSTRACT
Objective To investigate the effects of omeprazole on the expression and the activity of CYP2C19 in HepG2 cells. Methods MTT assay was performed to screen the concentration range of omeprazole which did not inhibit HepG2 cell proliferation. Real-time quantitative polymerase chain reaction(Q-PCR)were carried out to determine the effects of omeprazole(0,0.1,1 and 10 mg/L)on the expression of CYP2C19 mRNA,Western blot was carried out to determine the effect of(0,0.1,1 and 10 mg/L)on the ex?pression of CYP2C19 protein. After incubation of different concentrations of omeprazole(0,0.1,1,10 and 100 mg/L)with microsomes prepared from insect cells expressing human P450 isozyme,the fluorescence of the samples was detected in a plate reader to analyze if omeprazole inhibited the CYP2C19 activity. Results Omeprazole could down-regulate CYP2C19 mRNA and protein expressions of HepG2 cells in a dose-dependent manner. When the concentration of omeprazole reached 10 or 100 mg/L,the fluorescence intensities obviously decreased,indicating inhibited CYP2C19 activity. Conclusion Omeprazole inhibits the expression and the activity of CYP2C19 in HepG2 cell. When omeprazole is used in combination with drugs activated via CYP2C19 metabolism,their interaction should be considered carefully.
ABSTRACT
Objective To investigate the effect of activation of peroxisome proliferator-activated receptor β/δ ( PPARβ/δ)on protein synthesis and expression of angiotensin (Ang)Ⅱ-induced hypertrophic myocytes(MC) in vitro.Methods Hypertrophy in neonatal rat cardiac MC culture was established with AngⅡ, then the effect of GW0742 on hypertrophy was detected.The synthetic rate of protein in MC was detected by 3 H-leucine incorporation.mRNA and protein expression of atrial natriuretic IL-1βwas measured by reverse transcription-polymerase chain reaction ( RT-PCR) and Western-blotting. Results and Conclusion GW0742 could reduce the synthetic rate of protein in hypertrophic MC while down-regulating the mRNA and protein expression of IL-1β, but no changes were observed after treatment with DMSO.The result demonstrated that activation of PPAR beta/delta inhibited cardiac hypertrophy in vitro and this effect might be related to inflammatory factors.
ABSTRACT
Objective To investigate the effect of simvastatin on the expression of interleukin-1β(IL-1β) and tumor necrosis factorα(TNF-α) in cardiomyocyte of aging rat. Methods Primary cultures of cardiomyocyte were got from aging rats. Myocyte were divided into control group, dimerthyl sulfoxide(DMSO) group, and simvastatin group, which were treated respectively by cell culture medium, DMSO and simvastatin (1 and 10 μmol/L). The expression of IL-1β、 TNF-α mRNA was evalulated by RT-PCR, and contents of IL-1βand TNF-αprotein were detected by Western blot. Results RT-PCR showed that, compared with the aging model group, IL-1β and TNF-α mRNA expression of solvent group was no significant change (P>0.05), the mRNA expression of IL-1βand TNF-αin 1 and 10μmol/L simvastatin group was significantly lower (P0.05). Conclusions Simvastatin down-regulates IL-1βand TNF-αgene expression.
ABSTRACT
Objective To evaluate the effect of kojic acid( KA) on the immune system of mice after exposure to gam-ma-irradiation.Methods Twenty male C57BL/6 mice were divided into normal group, irradiation group, low/high doses of KA pretreated groups.Mice in normal group did not receive any treatment,while mice in other groups were sc injected with a single dose of sterile distilled water or KA(75 and 300 mg/kg, respectively) 27 h prior to a sublethal dose(4 Gy, 138.54 and 140.30 cGy/min, respectively) of whole body gamma-irradiation.The injected volume was calculated by 0.2 ml/20 g.Forty mice were sacrificed at day 2 and day 8 post-irradiation, respectively.The splenic lymphocyte transformation and spleen and thymus indexes were determined.Histopathological sections were produced, and the morphological changes were also observed.Results The splenic lymphocyte transformation capacity and spleen and thymus indexes of mice pre-treated with 300 mg/kg elatve mass KA were increased significantly ( P<0.01) compared with the irradiation group.The morphological changes in the spleen and thymus of mice in 300 mg/kg KA pretreated group were better than in the irradia-tion group.The above parameters of mice in irradiation group were injured severely in comparison with the normal group. Conclusion Acute radiation can damage the immune system of mice obviously.KA can enhance the transformation capaci-ty of lymphocytes and has marked protective effect on the immune system of mice after irradiation.
ABSTRACT
Objective To observe mRNA and protein expression of leukotriene B4(LTB4)receptor 2(BLT2)in mice during the course of development from colitis to colitis-associated cancer. Methods ICR mice were used to establish the animal model of colitis-associated colon cancer and randomly divided into control group and experimental group. We began to administer inducer on d0. Mice were sacrificed at 2,3,5,7,9,13,and 18w,respectively. Histopathological changes in colons were examined. The protein and mRNA expression of BLT2 in colons were measured by immunohistochemical assay and real-time quantitative PCR, respectively. Results Histological study showed that with the extension of time,the lesions of mice colons aggravated,first a mild inflammation,then atypical hyperplasia,and finally to colon cancer. Immunohistochemical staining showed that the expression of BLT2 protein was low in normal colon,but high in inflammatory lesions,especially in inflammatory cells. There was no BLT2 expression in atypical hyperplasia and cancer cells,while BLT2 was highly expressed in the stroma and lumans of cancer tissue. Compared with the control group,mRNA expression of BLT2 in the experimental group was significantly higher at 2,13 and 18w(P<0.05);and very significantly higher at 3,5,7 and 9w (P<0.01). Conclusion The mouse model of colitis-associated colon cancer was developed in this study. The expression of BLT2 changed in the course of colitis development,indicating that BLT2 may play an important role in the transition process from colitis to colon cancer.
ABSTRACT
Objective To investigate the G protein-coupled receptor kinase 2 (GRK 2) level in peripheral blood lymphocytes with cardiac func-tion in elderly patients with acute myocardial infarction. Methods This study enrolled 40 patients with acute ST-segment elevation myo-cardial infarction (STEMI) and 40 patients with unstable angina. All patients were 65 years or older. Cardiac function was evaluated by echocardiography, and the GRK 2 level in peripheral blood lymphocytes was measured. Patients with STEMI were followed up for 2 years. Results The GRK 2 level in peripheral blood lymphocytes was significantly higher in patients with STEMI than in patients with unstable angina, and was negatively correlated with left ventricular ejection fraction, cardiac output, stroke volume, and left ventricular fractional shortening. The GRK 2 level was significantly elevated in some patients with acute STEMI and poor cardiac function. Conclusions In-creased GRK 2 level in patients with acute STEMI may contribute to poor myocardial systolic function and myocardial remodeling. Meas-urement of the GRK 2 level in peripheral blood lymphocytes may assist in the evaluation of cardiac function and myocardial remodeling in elderly patients with acute STEMI.