1.Change of cardiac myocyte nuclear inositol 1,4,5- trisphospate receptor binding proterties in rat with myocardium ischemic reperfusion
Hong ZHANG ; Hong ZHOU ; Liangyi SI ; Lezhi ZHANG ; Huamei HE
Chinese Pharmacological Bulletin 2003;0(07):-
Aim Observing the alteration of cardiac myocyte nuclear inositol 1,4,5-trisphosphate receptor (IP_3R)binding proterties in rat subjected to myocardium ischemic reperfusion is to make it clear whether this change is involved in the molecule mechanism of cell apoptosis of rat with myocardial ischemic reperfusion. Method Apoptosis index of myocardial cell was determined using TUNEL assay.Extracting of cardiac myocyte nucleus was accomplished by saccharose density gradient centrifugation method,the binding proterties of nuclear IP_3R in different conditions were detected by radioligand binding assay.Results ①Myocardial cell apoptosis index in rat heart underwent 30 min regional ischemia and 3 h reperfusion was distinctly increased compared with sham-operated group(P
2.The role of arecoline on hepatic insulin resistance in type 2 diabetes rats.
Hong-Yan LING ; Qi-Xin YAO ; Zhu-Qing QI ; Si-Si YANG ; Jian-Qin HE ; Kai-Fang ZHANG ; Bi HU
Chinese Journal of Applied Physiology 2014;30(3):208-212
OBJECTIVETo explore the effects of arecoline on hepatic insulin resistance in type 2 diabetes rats and to elucidate its possible mechanism.
METHODSForty five Wistar rats were fed with high fructose diet for 12 weeks to induce type 2 diabetic rat model. rats were randomly divided into 5 groups (n = 8): control group, model group and model group were treated with different dose (0, 0.5, 1, 5 mg/kg) of arecoline. After 4 weeks, the fasting blood glucose, blood lipid and insulin level measured , mRNA expression of liver constitutive androstane receptor (CAR), pregnane X receptor (PXR), glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by reverse transcription polymerase chain reaction (RT-PCR), the protein expression of p-AKT and glucose transporter4 (GLUT4) were detected by Western blot.
RESULTS1.5 mg/kg arecoline could significantly decrease the level of fasting blood glucose, blood lipid, blood insulin level and liver G6Pase, PEPCK, IL-6, TNF-alpha mRNA level in type 2 diabetes rats. 1.5 mg/kg arecoline also could significantly increase CAR, PXR mRNA level and p-AKT and GLUT4 protein expression.
CONCLUSIONArecoline improved hepatic insulin resistance in type 2 diabetes rats by increasing the mRNA levels of CAR and PXR leading to the creased glucose metabolism and inflammation related genes expression.
Animals ; Arecoline ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; Diabetes Mellitus, Type 2 ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Glucose-6-Phosphatase ; metabolism ; Insulin Resistance ; Interleukin-6 ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Phosphoenolpyruvate Carboxykinase (GTP) ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; metabolism ; Receptors, Steroid ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism
3.Regulative role of progesterone in inflammatory reaction after traumatic brain injury in rats
Daowen SI ; Qingguo MA ; Dianyou HE ; Zhisheng KAN ; Jingshan MENG ; Yuxin ZHANG ; Ziming ZHANG
Chinese Journal of Trauma 2011;27(12):1140-1144
Objective To investigate the effect of progesterone on the expressions of inflammation-related factors of cortical cyclooxygenase-2 ( COX-2 ),prostaglandin E2 ( PGE2 ),inducible nitric oxide synthase (iNOS) and NF-κB in the cortex after traumatic brain injury (TBI) in rats so as to study the possible molecular mechanism of neuroprotective effect of progesterone on TBI.Methods Fortyfive male Spraque-Dawley rats were enrolled in the study and randomly divided into three groups,ie,sham operation group (n =15),TBI group (n =15) and progesterone treatment group (n =15).The rat model of TBI was duplicated with the improved Feeney' s method.The PROG treatment group was given i.p.injections of progesterone ( 16 mg/kg) at 1 and 6 hours after injury.The rats were sacrificed in three groups at 24 hours after injury and the specimens were removed.The changes of the positive cell numbers and protein level of COX-2,PGE2,iNOS and NF-κB in the cortex were examined by immunohistochemistry and Western blot.Results The positive cell numbers and protein levels of COX-2,PGE2,iNOS and NF-κB in the cortex of the TBI group were distinctly higher than those of the sham operation group (P<O.05).While the positive cell numbers and protein levels of COX-2,PGE2,iNOS and NF-κB in the cortex of the progesterone treatment group were distinctly lower than those of the TBI group ( P <O.05).Conclusions Progesterone may exert protective effect on TBI through inhibiting NF-κB activity,blocking the inflammation response course of NF - κB and iNOS and decreasing the expressions of COX-2 and PGE2.
4.Regulatory effects of IFN-γ on Treg cells from HIV/AIDS patients receiving HAART for one year
Quan ZHANG ; Yunhai YAO ; Yan HE ; Quan ZHOU ; Yuhuang ZHENG ; Si ZENG
Chinese Journal of Microbiology and Immunology 2014;34(1):15-18
Objective To investigate the regulatory effects of IFN-γon Treg cells from HIV/AIDS patients receiving highly active antiretroviral therapy (HAART) for one year.Methods Thirty HIV/A1DS patients whose CD4+T cells were below 350/μ1 were recruited for HAART therapy.Blood samples were collected at the time points of 0,24,48 weeks after HAART.PBMCs were isolated and randomly divided into two culture groups.One group was cultured directly in medium and another group was co-cultured with IFN-γ (40 pg/ml).The supernatants and cells were separated after 5 days of culture for analysis.The concentrations of IL-12 and CD4+CD25+Foxp3 Treg cells were measured by ELISA and flow cytometry,respectively.Results The levels of IL-12 in the supernatants from the culture without IFN-γ at time points of 0,24,48 weeks after HAART were lower than those from the co-cultured group [(37.02±12.76) vs (41.79± 15.02),t=2.336,P=0.03; (41.76±17.01) vs (47.2±14.26),t=2.702,P=0.014; (48.01± 11.84) vs (53.44± 11.30),t =3.14,P =0.003].The percentages of CD4+ CD25 + Foxp3 Treg cells in CD4+ T cells from the direct-cultured group were higher than those from the co-cultured group at the three time points [(10.41±1.10)% vs (2.40±1.11)%,t=13.89,P=0.000; (8.33±2.03)% vs (1.99± 0.86)%,t=12.93,P=0.000; (5.65±1.55)% vs (1.32±0.73)%,t=10.61,P=0.000].Moreover,the results within the same group at the time points of 0,24,48 weeks upon HAART were also significantly different.Conclusion With the interference of HAART,IL-12 levels were increased,while CD4+CD25+ Foxp3 Treg cells were decreased in patients with HIV/AIDS.IFN-γ plays an important role in this process.
5.Research on the protective effect of diazoxide pretreatment on the blood-brain barrier of rats after cerebral ischemia/reperfusion injury
Pingping HE ; Hong ZHANG ; Dong HAN ; Weixin SI ; Yue ZHAO ; Chunyao LI
Journal of Chinese Physician 2016;18(9):1309-1312
Objective To investigate the effect and its mechanism of diazoxide on the blood-brain barrier (BBB) of rats after cerebral ischemia/reperfusion (I/R) injury.Methods Sixty Wistar rats were randomly divided into sham operation group,I/R group,and diazoxide pretreatment groups of low,middle,large dose (5,10,20 mg/kg).The I/R models of rats were performed to undergo middle cerebral artery embolism by thread.BBB permeability was estimated by Evans blue (EB) dyeing,transmission electron microscope (TEM) was used to observe the modification of interendothelial tight junction (TJ) of capillaries.The expression of aquaporin-4 (AQP4) in every rat brain tissues was detected by immunity histochemistry technique.Results (1) Compared to sham operation group,the permeability extent of EB were significantly increased by I/R,which was distinctly attenuated in middle and large dose of diazoxide pretreatment rats,while no obvious changes were found between I/R and low dose groups.(2) TEM showed that TJ of the brain tissue opened after I/R injury and no significant opening of TJ was observed in middle and large dose of diazoxide preconditioning groups.(3) Compared to sham operation group,the expression of AQP4 in the brain tissue of the I/R group was apparently increased (P <0.01).Compared to I/R group,the expression of AQP4 was apparently increased in middle and large dose pretreatment groups (P < 0.01),and there were no obvious difference between low dose group and the I/R group.Conclusions Preconditioning of ischemia/reperfusion injury with diazoxide protects the blood-brain barrier,which may due to keep the TJ closed and decrease expression of AQP4 protein.
6.Research Progress in Drug Interactions of Haloperidol
Kai LEI ; Yuan HUANG ; Si ZHANG ; Guofang HE ; Dong LIU ; Xiuhua REN
China Pharmacist 2017;20(2):334-337
Objective:To summarize the drug interactions of haloperidol used in combination with the other drugs to provide refer-ence for safe, reasonable and effective use of haloperidol in clinics. Methods:By retrieving Micromedex? , Pubmed, CNKI and so on, the interactions between haloperidol and the other drugs were summarized and analyzed. Results:The effect of haloperidol was on do-pamine receptors, and haloperidol was mainly metabolized by hepatic cytochrome P450 ( CYP) enzymes. When haloperidol was com-bined with the other drugs, significant interactions of pharmacokinetics and pharmacodynamics were induced by affecting CYP enzymes or dopamine receptor. Conclusion:In clinical practice, the other drugs combined with haloperidol should be reasonable and careful to ensure safe, effective and rational drug use.
7.Dynamic observation of EB virus DNA load before and after the treatment in patients with nasopharyngeal carcinoma and its clinical significance.
Yongli WANG ; Yongfeng SI ; Ning HE ; Yangda QIN ; Zheng ZHANG ; Jinjie SUN ; Yong YANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2014;28(11):801-804
OBJECTIVE:
Dynamic observation of Epstein-Barr virus (EBV) DNA load before and after the treatment in patients with Nasopharyngeal carcinoma (NPC), predicting the incidence of distant metastasis and offering more personalised choice of therapies.
METHOD:
Fifty-four cases of patients with NPC were taken by fluorescence quantitative PCR assay of EBV DNA load before and after the treatment, all patients were followed up according to plan and carried out the progression-free survival (PFS) and overall survival (OS).
RESULT:
EBV DNA load in plasma of patients with NPC can partly reflect the clinical characteristics of patients; EBV DNA load in some patients with distant metastasis was higher than those patients with continuous remission when they were not started treatment (P < 0.05); For those patients whose EBV DNA copies were lower than 20,000 copies/mI before the treatment, the progression-free survival and overall survival rates were higher than those high expression patients, and the difference were statistically significant (PF < 0.01 and P < 0.05).
CONCLUSION
The EBV DNA load in the plasma of NPC patients can partly predict the occurrence of distant metastases before treatment.
Adolescent
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Adult
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Aged
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Carcinoma
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DNA, Viral
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blood
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Female
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Herpesvirus 4, Human
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genetics
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Humans
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Male
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Middle Aged
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Nasopharyngeal Carcinoma
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Nasopharyngeal Neoplasms
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therapy
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virology
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Neoplasm Metastasis
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Viral Load
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Young Adult
8.Application of temperature sensitive yeast models with definite target in the screening of potential human Pin1 inhibitors.
Jing ZHANG ; Xiaomin HAN ; Wenhui HU ; Zongru GUO ; Xiaobo HE ; Shuyi SI
Acta Pharmaceutica Sinica 2014;49(6):854-60
This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
9.Comparison of marker gene expression changes in different mouse models of cardiac hypertrophy
Hongwei KAN ; Wenwen SI ; Yanyan YIN ; Can HE ; Jie CHENG ; Chunyan WANG ; Qiongguang ZHANG ; Yan YANG
Chinese Pharmacological Bulletin 2016;(2):274-278
Aim To explore the differences in hyper-trophic marker genes such as atrial natriuretic peptide ( ANP) , brain natriuretic peptide ( BNP) and β-myo-sin heavy chain (β-MHC) genes in different models of cardiac hypertrophy. Methods Respectively using re-nal abdominal aortic coarctation ( AAC) , arteriovenous fistula ( AVF) and isoproterenol ( ISO) methods to es-tablish C57BL/6 mouse model of cardiac hypertrophy. After modeling, each mouse ’ s body weight ( BW ) , heart weight ( HW) and left ventricular weight ( LVW) were weighed, and the heart weight ( HW/BW) and left ventricular index ( LVW/BW ) were calculated;myocardium by HE staining, pathological morphologi-cal changes were observed; myocardium by immuno-histochemistry, ANP, BNP and β-MHC protein ex-pression was observed;myocardium by Real-time PCR detection, ANP, BNP and β-MHC mRNA expression was observed. Results Compared with control group, HW/BW and LVW/BW were increased in three mod-els. Through the light microscope, each mouse model showed varying degrees of cardiac hypertrophy. ANP, BNP and β-MHC were increased in the protein and mRNA expression. Compared with AAC group, AVF and ISO groups’ myocardial tissue ANP, BNP and β-MHC expression were decreased in the protein and mRNA expression. Conclusions Three cardiac hy-pertrophy models are successful. Cardiac tissue ANP, BNP and β-MHC expression in AAC model exceeds AVF and ISO model.
10.Practice of ‘student-centered’ physiological teaching reform
Ketao MA ; Xinzhi LI ; Zhongshuang ZHANG ; Li LI ; Lei ZHAO ; He ZHU ; Junqiang SI
Chinese Journal of Medical Education Research 2012;(12):1251-1253
‘Student-centered’ teaching model is the needs of higher medical education.In the process of education,we carried out comprehensive and systematic reforms by satisfying students' needs and improving students' ability as the main line.These reforms included change of teaching methods (the basic theory combined with clinical knowledge),increase of innovative experiments and change of evaluation system.These results showed that students were interested in these reforms,the innovation abilities of students were improved and students could pay more attention to the process of learning.