1.Effects of pravastatin on the proliferation of vascular smooth muscle cells and cell adhesion induced by lysophosphatidylcholine
Huafei DENG ; Yan XIONG ; Zheng GUO
Chinese Pharmacological Bulletin 2003;0(12):-
Aim This study was designed to investigate the effects of pravastatin,a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor,on vascular smooth muscle cells (VSMCs) proliferation and leukocyte-endothelial cell adhesion induced by lysophosphatidylcholine (LPC).Methods Cultured VSMCs from rabbit thoracic aorta were incubated with various concentrations of LPC in the absence or presence of different concentrations of pravastatin. MTT was used to evaluate the proliferation of VSMCs. We determined the effects of LPC and pravastatin on neutrophil K562 adhesion to endothelial cells ECV304 by directly counting non-adhesive K562 cells.Results Incubation of VSMCs with LPC (1~10 ?mol?L -1) stimulated proliferation of VSMCs in a time- and dose-dependent manner,while pravastatin (0.3~1 mmol?L -1) treatment prevented the proliferation of VSMCs caused by LPC. Moreover, incubation of ECV304 with 3 ?mol ? L -1 LPC for 12 h significantly enhanced K562 cells adhesion to endothelial cells, whereas pretreatment with pravastatin reduced leukocyte-endothelial cell adhesion. Conclusion These results suggest that pravastatin can antagonize the effects of VSMCs proliferation and leukocyte-endothelial cell adhesion induced by LPC.
2.Expressions of LC3B, P62 and Beclin1 in the liver of rats with chronic fluorosis and the role of autophagy in liver injury induced by fluorosis
Li HE ; Yanni YU ; Lili GUO ; Yan LINGHU ; Chaonan DENG
Chinese Journal of Endemiology 2021;40(5):355-362
Objective:To observe the protein and mRNA expressions of microtubule-associated protein 1 light chain 3 (LC3)B, P62 and Beclin1 in the liver of rats with chronic fluorosis, and to explore the role of autophagy in pathogenesis of liver injury induced by fluorosis.Methods:Using a group design, 54 SD rats were divided into 9 groups according to their weight (100 - 120 g) using a random number table method, each group with 6 rats, half male and half female. They were control group (NC group), low fluoride group (LF group), high fluoride group (HF group), NC + rapamycin (RAP) group, LF + RAP group, HF + RAP group, NC + chloroquine (CQ) group, LF + CQ group, and HF + CQ group. The NC group drank tap water (fluoride concentration was 0.5 mg/L), LF group drank fluoride water (fluoride concentration was 5.0 mg/L), HF group drank fluoride water (fluoride concentration was 50.0 mg/L); NC + RAP group, LF + RAP group and HF + RAP group were fed with corresponding drinking water, respectively, for 3 months, and then RAP (1.5 mg/kg) was intraperitoneally administered for 10 d; NC + CQ group, LF + CQ group and HF + CQ group were fed with corresponding drinking water, respectively, for 3 months, and then CQ (60 mg/kg) was intraperitoneally administered for 10 d. Bone and 24-hour urine samples of rats in each group were collected to detect the contents of bone fluoride and urine fluoride; liver histomorphological changes were observed through hematoxylineosin staining; protein and mRNA expressions of LC3B, P62 and Beclin1 in liver were detected by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.Results:Compared with the NC group [(0.03 ± 0.00) mg/kg, (0.34 ± 0.08) mg/L], the contents of bone fluoride [(3.86 ± 0.08) mg/kg] and urine fluoride [(1.11 ± 0.16) mg/L] in HF group were higher ( P < 0.05). In the NC group, the lobule structure of liver tissue was clear, the hepatic cords were arranged in order, and the cell structure was normal. There were different degrees of hepatocyte edema in LF and HF groups. After intraperitoneal injection of RAP, compared with the corresponding fluoride group, the morphology of hepatocytes did not change significantly. After intraperitoneal injection of CQ, compared with the corresponding fluoride group, the liver cells showed obvious edema, and the degree of edema aggravated with the increase of fluoride concentration. Compared with the NC group, the protein expressions of LC3B and Beclin1 in HF group were higher ( P < 0.05), and the protein expression of P62 was lower ( P < 0.05). After intraperitoneal injection of RAP, the protein expressions of LC3B and P62 in LF + RAP group was lower than that in LF group ( P < 0.05); Compared with HF group, the protein expressions of LC3B and Beclin1 in HF + RAP group were lower ( P < 0.05). After intraperitoneal injection of CQ, protein expression of P62 in LF + CQ group was higher than that in LF group ( P < 0.05); Compared with HF group, protein expression of P62 in HF + CQ group was higher ( P < 0.05). Conclusions:Early (3 month) fluoride intake could promote autophagy and induce edema of hepatocytes in rats, and RAP had similar effects. CQ may induce liver injury by inhibiting autophagy of hepatocytes.
3.Simultaneous Determination of 10 Kinds of Chemical Components in Processed Products of Rhei Radix et Rhizoma
Yonggang YAN ; Limin YIN ; Hongyan WANG ; Lingling GUO ; Chong DENG
China Pharmacy 2016;27(27):3839-3842
OBJECTIVE:To establish a method for the contents of gallic acid,catechin,sennosides B,aloe-emodin,rhein, emodin,chrysophanol,physcion,chrysophanol-1-O- glucoside and emodin-8-O- glucoside in Rhei Radix et Rhizoma,Jiu Rhei Radix et Rhizoma,Shu Rhei Radix et Rhizoma,Rhei Radix et Rhizoma tan,Cu Rhei Radix et Rhizoma,and analyze the differ-ences. METHODS:HPLC was performed on the column was Hypersil C18 with mobile phase of methanol- 0.2% acetic acid(gradi-ent elution)at a flow rate of 1.0 ml/min,the detection wavelength was 260 nm,column temperature was 25 ℃,injection volume was 10 μl. RESULTS:The linear range was 0.252 5-4.040 0 μg for gallic acid(r=0.999 6),0.600 0-9.600 0 μg for catechin(r=0.999 6),0.297 4-4.758 4 μg for sennosides B(r=0.999 9),0.001 8-0.028 8 μg for aloe-emodin(r=0.999 9),0.005 0-0.080 0 μg for rhein(r=0.999 9),0.019 0-0.304 0μg for emodin(r=0.999 8),0.380 2-6.083 2μg for chrysophanol(r=0.999 7),0.008 2-0.131 2μg for physcion(r=0.999 8),0.126 0-2.016 0 μg for chrysophanol-1-O-glucoside(r=0.999 6)and 0.111 3-1.780 8 μg for emo-din-8-O-glucoside (r=0.999 8);RSDs of precision,stability and reproducibility tests were lower than 3.0%;recoveries were 96.17%-97.21%(RSD=1.67%,n=6),97.60%-100.54%(RSD=2.55%,n=6),99.45%-101.32%(RSD=1.63%,n=6), 95.31%-98.19%(RSD=2.42%,n=6),98.99%-100.35%(RSD=1.86%,n=6),98.95%-101.21%(RSD=2.17%,n=6), 99.81%-100.62%(RSD=1.66%,n=6),96.78%-98.52%(RSD=1.99%,n=6),97.80%-100.14%(RSD=3.32%,n=6) and 97.40%-101.24%(RSD=2.89%,n=6). Compared with Sheng Rhei Radix et Rhizoma,the contents of gallic acid,catechin,sen-nosides B and anthraquinones in Cu Rhei Radix et Rhizoma,Jiu Rhei Radix et Rhizoma and Rhei Radix et Rhizoma tan decreased. The contents of catechin,sennosides B and anthraquinones in Shu Rhei Radix et Rhizoma. Catechin,sennosides B,chrysopha-nol-1-O- glucoside,aloe-emodin and rhein were not detected in Dahuang tan. CONCLUSIONS:The method is simple with good precision,stability and reroducibility,and can be used for the simultaneous determination of 10 chemical components in processed products of Rhei Radix et Rhizoma;there were significant differences in contents of 10 chemical components in processed prod-ucts of Rhei Radix et Rhizoma.
4.Thought and Method of Clinical Therapeutic Evaluation System Constructing of Traditional Chinese Medicine in Coronary Heart Disease
Jiajuan GUO ; Yingzi CUI ; Yan WEI ; Yue DENG
World Science and Technology-Modernization of Traditional Chinese Medicine 2013;(5):1037-1040
The overall concept is the core theory of traditional Chinese medicine ( TCM ) diagnosis and treat-ment system. During the process of building TCM effect evaluation on coronary heart disease (CHD), with the defined connotation and extension of heart diseases , except the consideration on its clinical symptoms , TCM four diagnosis and various current modern cardiovascular disease diagnostic methods should be organically com-bined according to the original macro basis . The micro quantitative evaluation is given on therapeutic effect of disease treatment in order to construct the complete TCM effect evaluation system.
5.Analysis of Factors Related to Efficacy of Peach kernel-Rheum palmatum Couplet Medicines in TCM For-mula
Lingling GUO ; Yonggang YAN ; Hongyan WANG ; Limin YIN ; Chong DENG
China Pharmacy 2017;28(23):3188-3191
OBJECTIVE:To study the influential factors related to efficacy of Peach kernel-Rheum palmatum couplet medi-cines in TCM formula,and to reveal the general regularity of compatibility environment,common ratio,processing variety and dosage forms of P. kernel-R. palmatum couplet medicines. METHODS:Using Chinese Medical Prescription Selected Dictionary ed-ited by Peng Huairen as data source,142 formulas of P. kernel-R. palmatum couplet medicines were collected. By establishing data-base,compatibility types of P. kernel-R. palmatum couplet medicines,as well as common ratio,processed prodact,dosage form were classified statistically. The influential factors related to efficacy of P. kernel-R. palmatum couplet medicines with different pro-portions were summarized. RESULTS:The efficacy of P. kernel-R. palmatum couplet medicines could be divided into 6 aspects and 11 roles,including activating blood circulation to dissipate blood stasis(activating blood to relieve pain,promoting blood circula-tion to eliminate disease,activating blood to promote menstruation,breaking stagnant and eliminating blood stasis),eliminating carbuncle and detoxicating(cleaning intestine and clearing away the pathogenic heat of lung,eliminating carbuncle and expelling pus,eliminating sore and detoxicating),expelling the pathogenic heat to loosen the bowels,warming yang for dispelling cold,forti-fying the spleen and nourishing the stomach,relaxing tendon and activating blood. The compatibility environment of P. kernel-R. pal-matum couplet medicines were mainly compatible with TCM for activating qi to eliminate stasis,activating blood to promote menstru-ation,breaking stagnant and eliminating blood stasis,expelling the pathogenic heat to expel stasis. The ratio of P. kernel to R. palma-tum ranged 1 : 8-4 : 1,and the ratio ranged 1 : 8-3 : 1 when performing the role of actirating blood circalation to dissipate blood stasis. Common processed products were crude P. kernel and prepared R. palmatum. Common dosage forms were mainly decoction,pill and powder. CONCLUSIONS:Compatibility environment,ratio,processing varieties,dosage forms influence the effects of P. kernel-R. palmatum couplet medicines,especially compatibility environment.
6.Progress in the biomarker discovery for drug-induced liver injury.
Lei-yan HE ; Yao-xue GUO ; Chun LI ; Ye DENG ; Qi-zhi ZHANG ; Wen-xing PENG
Acta Pharmaceutica Sinica 2015;50(8):959-965
The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers
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blood
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urine
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Chemical and Drug Induced Liver Injury
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diagnosis
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Humans
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Sensitivity and Specificity
7.Effects on rat hearts induced by three kinds of band electromagnetic radiation
Yan DOU ; Dewen WANG ; Minfeng ZHANG ; Ruiyun PENG ; Junsong ZHANG ; Jiexi DENG ; Yihe GUO
Chinese Journal of Radiological Medicine and Protection 2009;29(1):114-116
Objective To investigate the effects on rat hearts induced by three kinds of band electromagnetic radiation (X-band, S-band and Electromagnetic pulse (EMP))and the differences of injury grade. Methods 180 healthy male Wistar rats were randomly divided into four groups:control group (n = 36) and three experimental groups (n = 48) treated with X-band, S-band high power microwave and EMP, respectively. At different time-points (6 hours,1, 3, 7, 14, 28 days,6 months and 12 months) after irradiation, the rats were killed and the pathological changes of the heart tissues were observed. Results The rat hearts of three experimental groups were differently injured, but the change character was similar. The injury was more and more serious at 6 hours -7 days:deranged cardiomyofilaments, decreased glycogen, Pyknosis;lysed Purkinje cells;swelling matrix and serous exudates. The injured hearts showed convalesecence at 14-28 days, and returned to normal progressively at 6-12 months.compared with the injured hearts irradiated by the three different band wave electromagnetic at the same time: the hearts were injured most seriously irradiated by X-band high power microwave(HPM), and slighter for those by S-band HPM, most slightest for those by EMP. Those in control group were normal. Conclusions Three kinds of band wave electromagnetic radiation injure the rat hearts differently. The injury grades are X > S > EMP. The research indicates that the shorter wave length or higher frequency make rat hearts injure more seriously, and need the longer time to resume.
8.Evaluation of the left ventricular longitudinal strain in patients with myocardial ischemia by two-dimensional speckle tracking imaging
Qing DENG ; Qing ZHOU ; Jia HUANG ; Jinling CHEN ; Bo HU ; Yan JIA ; Tian WU ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2011;20(8):648-651
Objective To assess left ventricular(LV) longitudinal strain in patients with coronary heart disease by two-dimensional speckle tracking imaging (2DSTI),and to explore the clinical value of 2D longitudinal strain in detecting myocardial ischemia. Methods Forty-four patients with coronary heart disease (CHD group) and 28 age-matched subjects (control group) were enrolled into this study. The two-dimensional data were obtained in apical 4-chamble, 2-chamber and long axis view. And the longitudinal strains of every segments, the average longitudinal strain of LV 18 segments (SL18), the average longitudinal strain of 12 segments (SL12,excluded the 6 apical segments) were analyzed. Results In the patients with CHD, the longitudinal strain of ischemia segments and the global LV longitudinal strain were significantly decreased than that of the control subjects. Both in patients with CHD and in control subjects,the longitudinal strains in apical segments were higher than that of middle and basal segments. There was significant difference between SL18 and SL12 ( P=0.027 in CHD group and P =0.003 in control group).Receiver operating curve (ROC) analysis demonstrated that the cutoff point of SL18 to detect myocardial ischemia was - 18.8% (sensitivity 80.2% and specificity 74.1% ) ,and the cutoff point of SL12 to detect myocardial ischemia was - 17.8% ( sensitivity 81.7% and specificity 85.6% ). Conclusions 2D longitudinal strain was sensitive to detect myocardial ischemia, SL12 was better than SL18 in detecting myocardial ischemia. 2DSTI might be useful for identifying patients with severe CHD.
9.Assessment of left ventricular function and infarct size of acute myocardial infarction by automated function imaging
Bo HU ; Qing ZHOU ; Jia HUANG ; Yan JIA ; Tian WU ; Qing DENG ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2011;20(9):742-746
Objective To assess the left ventricular function of patients with acute myocardial infarction (AMI) and its correlation with cardiac troponin T (cTnT) and specific manifestation of electrocardiogram (ECG) by automated function imaging (AFI) of two-dimensional speckle tracking imaging.Methods Forty-six AMI patients who had AMI for the first time and had been treated by primary percutaneous coronary intervention and 30 healthy controls who were age and sex-related to infarct group were involved.The values of cTnT within 24 hours after admission of AMI patients were recorded and the values of ST segment elevation were measured accurately.All the subjects were analyzed for longitudinal peak systolic strain (LPSS) values and the bull' s eyes by AFI.Results Compared to control group, left ventricular ejection fraction (LVEF), global and infarcted LPSS of infarct group were significantly different and the values of ST elevation of infarct group were higher than those of control group.Both global,infarcted segmental LPSS were significant closely correlated to LVEF and cTnT,respectively (P<0.001,all).Both global, infarcted segmental LPSS were correlated to ST elevation (P <0.05,all).Global LPSS had the closest correlation with LVEF (r = -0.565, P<0.001) and so did infarcted LPSS with cTnT (r = 0.432, P <0.01).Conclusions As a procedural simple and rapid diagnostic tool,AFI provides reliable and useful information of the assessment of AMI.Both global and infarcted segmental LPSS have well described left ventricular function of AMI patients.Compared to LVEF, LPSS was more closely correlated to cTnT and ST segment elevation, which meant that LPSS was more sensitive and more closely related to real infarct size and actual involved range of AMI.
10.Assessment of the correlation between time during admission to percutaneous coronary intervention and left ventricular function recovery of acute myocardial infarction by two-dimensional speckle tracking imaging
Bo HU ; Qing ZHOU ; Jia HUANG ; Yan JIA ; Tian WU ; Qing DENG ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2011;20(11):930-934
Objective To assess the correlation between time during admission to percutaneous coronary intervention (PCI) and left ventricular function recovery of acute myocardial infarction (AMI) by two-dimensional speckle tracking imaging (STI).The clinical value of STI in assessing therapeutic effect of AMI treated by PCI and estimation of the prognosis were discussed.Methods Sixty-one AMI patients who had AMI for the first time and had been treated by primary PCI were enrolled.Dynamic images were acquired before PCI,at 7 days after PCI and 30 days after PCI and analyzed by STI.The time during admission to PCI of AMI patients was recorded accurately.Dynamic images were analyzed for longitudinal peak systolic strain (LPSS) values (global,infarcted area) by STI.According to the comparison of left ventricular ejection fraction(LVEF) before PCI and 30 days after PCI,patients were divided into left ventricular function improved group (ΔLVEF≥5 %) and not-improved group,and the values of LPSS and time during admission to PCI were compared between the two group respectively.Results Compared to not-improved group,the time during admission to PCI in improved group was lower ( P <0.001),infarcted segmental LPSS at 7 days after PCI ( P <0.05) and both global ( P <0.001) and infarcted segmental LPSS ( P <0.001) at 30 days after PCI in improved group were higher than those in not-improved group.Linear regression analysis showed that both global and infarcted segmental LPSS were significant correlated to LVEF respectively ( P <0.001,all).Infarcted segmental LPSS at 7 days after PCI were correlated to the time during admission to PCI ( P <0.05).LVEF ( r =0.303,P <0.05),global ( r =0.300,P <0.05)and infarcted segmental LPSS ( r =0.590,P <0.001) at 30 days after PCI were correlated to the time during admission to PCI.Conclusions STI provides reliable and useful clinical information for the assessment of therapeutic effect of AMI treated by PCI and estimation of the prognosis by sensitively presenting the close correlation between time during admission to PCI and left ventricular function recovery of AMI patients.