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This study is aimed to investigate the intervention effect and possible mechanism of ophiopogonin D( OPD) in protecting cardiomyocytes against ophiopogonin D'( OPD')-induced injury,and provide reference for further research on toxicity difference of saponins from ophiopogonins. CCK-8 assay was used to evaluate the effect of OPD and OPD' on cell viability. The effect of OPD on OPD'-induced cell apoptosis was measured by flow cytometry. Morphologies of endoplasmic reticulum were observed by endoplasmic reticulum fluorescent probe. PERK,ATF-4,Bip and CHOP mRNA levels were detected by Real-time quantitative polymerase chain reaction( PCR) analysis. ATF-4,phosphorylated PERK and e IF2α protein levels were detected by Western blot assay. RESULTS:: showed that treatment with OPD'( 6 μmol·L-1) significantly increased the rate of apoptosis; expressions of endoplasmic reticulum stress related genes were increased. The morphology of the endoplasmic reticulum was changed. In addition,different concentrations of OPD could partially reverse the myocardial cell injury caused by OPD'. The experimental results showed that OPD'-induced myocardial toxicity may be associated with the endoplasmic reticulum stress,and OPD may modulate the expression of CYP2 J3 to relieve the endoplasmic reticulum stress caused by OPD'.
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Humans , Apoptosis , Cardiotonic Agents , Pharmacology , Cells, Cultured , Endoplasmic Reticulum Stress , Myocytes, Cardiac , Saponins , Pharmacology , Spirostans , PharmacologyABSTRACT
OBJECTIVE To investigate the expression differences of seven cytochrome P450 (CYP) isoforms between L02, LX-2 and HepG2 cells and identify the most suitable cell type for different CYP researches. METHODS L02, LX-2 and HepG2 cells were treated with omeprazole (Ome), dexamethasone(Dex), phenobarbital sodium (Phe), isoniazid (Iso) and rifampicin (Rif) at 5, 10, 20 and 40 μmol • L-1. Cell viability was analyzed by CCK-8 assay. The gene expressions of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 in LX-2 cells were assessed by real-time quantitative PCR (RT-qPCR). The protein expressions of these seven CYP isoforms in L02, LX-2 and HepG2 cells were assessed by Western blotting. Furthermore, CYP3A4 activity in the three types of cells treated with Rif 5, 10, 20 and 40 μmol • L-1 for 24 h was validated by Luciferin-PFBE. RESULTS Cell viabilities of all the three hepatocytes were over 80% when exposed to Ome, Dex, Phe, Iso and Rif (≤40 μmol • L-1) for 24 h. According to the RT-qPCR, Phe could significantly enhance the gene expressions of CYP2B6 (P<0.05) and CYP2D6 (P<0.01) in LX-2 cells. The results of Western blotting exhibited protein expression differences of seven CYP isoforms between L02, LX-2 and HepG2 cells treated with Ome, Dex, Phe, Iso and Rif (≤40 μmol-L-1) for 24 h. CYP2C9 [Integrated absorbance (IA)=1.58±0.07], CYP2C19 (IA= 0.95±0.03) and CYP3A4 (IA=1.29±0.05) had higher expression abundances in L02 cells, CYP2B6 (IA= 1.48±0.01) and CYP2D6 (IA=1.46±0.02) in LX-2 cells, and CYP1A2 (IA=1.62±0.19) and CYP2E1 (IA= 1.49±0.10) in HepG2 cells. Additionally, CYP3A4 activity in L02, LX-2 and HepG2 cells could not be up-regulated by Rif. CONCLUSION The most suitable cell type for different CYP researches is L02 for CYP2C9, CYP2C19 and CYP3A4, LX-2 for CYP2B6 and CYP2D6, HepG2 for CYP1A2 and CYP2E1, respectively.
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Objective: To investigate the diagnostic value of combined examination of copeptin and high sensitivity cardiac troponin T (hs-cTnT) in patients at the early stage of acute myocardial infarction (AMI) . Methods: A total of 272 patients were enrolled in this study, all of them suffered from chest pain and admitted within 4 hours. The patients were divided into 4 groups according to coronary artery angiography (CAG) results. Control group, the patients with normal CAG,n=64, UAP group (unstable angina pectoris),n=50, STEMI group,n=82, NSTEMI group,n=76. All patients received in-hospital observation, plasma levels of copeptin and hs-cTnT were examined at admission and at 6 hours after the chest pain respectively. Results: Within 4 hours of chest pain, combined examination of copeptin and hs-cTnT had the higher sensitivity for diagnosing AMI than a single detection of hs-cTnT with the cut-off point of hs-cTnT ≤ 14ng/L and Copeptin < 14pmol/L. In NSTEMI group, the AUC (area under curve) for combined examination was 0.97 (95% CI 0.88-0.99), AUC for single hs-cTnT detection was 0.75 (95% CI 0.62-0.87),P<0.05. In STEMI group, the AUC for combined examination was 0.97 (95% CI 0.88-0.99), AUC for single hs-cTnT detection was 0.74 (95% CI 0.60-0.88),P< 0.05. The AUC for combined examination of copeptin and hs-cTnT in diagnosing early AMI was 0.912 (95% CI 0.812-0.961) which was higher than single detection of hs-cTnT, AUC 0.851 (95% CI 0.713-0.936), Z=2.553,P<0.05. Conclusion: Combined examination of copeptin and hs-cTnT had the higher sensitivity and accuracy for diagnosing the patients at the early stage of AMI, it may help the risk stratiifcation of chest pain which is valuable in clinical practice.
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Mini-clinical evaluation exercise(Mini-CEX) is a new tool used to evaluate clinical skill of internal residents.Through necessity,operation and practice of Mini-CEX applied in internal residents' clinical teaching,the paper makes it known that Mini-CEX is consistent with six requisitions of resident competence raised by Accreditation Council of Graduate Medical Education (ACGME).It increases medical and directorial quality,and is combined with doctor training abroad.Mini-CEX should be spread in training and examination of internal residents.
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Objective To explore the relationship between the extent of coronary artery lesions and plasma brain natriurefic peptide(BNP)levels in the patients with coronary artery disease(CAD)except for congestive heart failure(CHF).Method Seventy CAD patients without CHF evidenced by dinical manifestation and coronary arte- riography(CAG)from Cardiology Depamnent of the First Affiliated Hospital of Zhejiang University School of Medicine,China,were enrolled in the study.These patients were diagnozed under coronary arteriography(CAG) during March to May of 2007.They were divided into 3 groups:stable angina goup(24 patients),unstable angina group(25 patients),myocardial infarction group(21 patients).Twenty patients without coronary history and with normal CAG served as controls.Plasma BNP concentrations were measured with ELASA before CAG.The coronary lesion vessels and scores were estimated after CAG.The relationship between BNP levels and the coronary lesion vessels,as well as scores in CAD was analyzed.The data were expressed as(x±s)and was analyzed by using 2 independent samples test and spearman correlation with SPSS 13.0.A P value less than 0.01 indicated statistical significance.Results The plasma BNP concentrations in the patients,especially in the patients with myocardial infarction,were significantly higher than those in the controls.Spearman analysis showed that there was a positive correlation between the BNP levels and coronary lesion vessels(r1=0.309,P=0.01),also between BNP and coronary lesion score(r2=0.279,P=0.01).Conclusions In the patients without congestive heart failure,the more serious the coronary artery lesions,the higher the plasma BNP concentrations were.The degree of myocardial ischemia caused by coronary artery lesions was correlated with the plasma BNP level.Plasma BNP concentration could be valuable for the extent of coronary artery lesions in the patients of coronary artery disease.
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Objective To evaluate the value of coronary arteriongraphy(CAG)in diagnosing angina.Methods 219 patients with angina in clinical analysis were selected and divided into 2 groups:the stable angina(SA)group and unstable angina(UA)group.They all were accepted CAG first time.Then analysis were carried out between clinical diagnosis and results of CAG.Results The total positive rate of CAG in diagnosing angina is 58.90%.The positive rate of SA group(56.52%)shows no significant difference with that of UA group(60.00%).Single vessel lesion and multiple vessels lesion of SA group have little difference,however,the main coronary artery lesions of UA group is single vessel.Conclusions CAG is extremely important in diagnosing angina,but it has its own limit.Experience and new technique should be applied to retrieve locatization of CAG.