1.Application of PPARαtransgenic mice in the evaluation of drug toxicity
Yinli HE ; Xun GUO ; Xianli ZHAO ; Yanyu PEI ; Jingjiang SUN ; Hong GAO
Acta Laboratorium Animalis Scientia Sinica 2015;(3):316-320
Objective To explore whether PPARαtransgenic mice are more sensitive animal models in the evalua-tion of toxicity of PPARαagonists.Methods Twenty-eight 8-week old PPARαtransgenic mice (Tg) and 28 C57BL/6J mice (WT) with half males and half females were randomly divided into high dose group (400 mg/kg of clofibrate), low dose group (30 mg/kg of clofibrate) and solvent control group (10%sodium carboxymethyl cellulose ).The time of gavage administration lasted 28 days.The blood biochemistry , organ coefficient and pathological changes of the heart , liver, kid-neyweretestedafterthedrugadministration.Thegrowthofmicewasalsorecorded.Results ①Bloodbiochemistry:Com-pared with the WT male administration group , in the Tg male administration group , the levels of blood creatinine ( CREA) and aspartate aminotransferase (AST) were markedly increased (P<0.01, P<0.05).② Organ coefficient: Compared with the Tg control group, the kidney coefficients of Tg administration group were significantly increased (P<0.01,P<0.05).③Histopathology:Compared with the WT administration group , the pathological damages of liver and kidney were more serious in the Tg administration group .Conclusions Compared with C57BL/6J mouse, PPARαtransgenic mice are more sensitive in evaluation of hepatotoxicity and nephrotoxicity of PPARαagonists .It is a new animal model .
2.Alterations in KCNJ4 gene expression in human temporal lobe epilepsy
Xun-Yi WU ; Zhen HONG ; Xiang GAO ; Guo-Xing ZHU ; Chuan-Zhen LV ;
Chinese Journal of Neurology 2000;0(04):-
Objective To evaluate the possible molecular pathogenesis of intractable temporal lobe epilepsy. The potassium ion channel gene KCNJ4 encodes one of the subfamilies of Kir channels, Kir2.3 subunit, which may play an important role in modulating neuronal excitation. Interference in the function or expression of this gene would cause disturbance of ionic concentrations, thus leading to seizure activity. Methods Reverse transcription polymerase chain reaction (RT-PCR) and Western-blot analysis were used to measure the expression alterations of KCNJ4 mRNA as well as its protein product Kir2.3 channel in temporal cortex samples from patients who had undergone temporal lobectomy for intractable epilepsy (n=12). Tissue from 10 subjects who did not have epilepsy served as controls. Results The expression of KCNJ4 mRNA (0.438?0.178) and its protein Kir2.3 (M 50=0.063) were significantly decreased in epileptic brain compared with the controls (P
3.Effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction on myocardial apoptosis and relevant protein expressions in miniature swine phlegm and blood stasis type coronary heart disease model.
Ai-guo YAN ; Jian-xun LIU ; Xin-zhi LI ; Xiao-xia DONG ; Hong-kun LI
China Journal of Chinese Materia Medica 2015;40(11):2174-2179
There have been very few studies on the effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in inhibiting apoptosis in myocardial ischemial injury caused by coronary heart disease. In this experiment, Gualou Xiebai Banxia decoction combined with-Xuefu Zhuyu decoction were used to intervene the miniature swine phlegm and blood stasis type coronary heart disease model, in order to observe the effect of the combined prescription on the myocardial apoptosis and the expressions of Bcl-2, Bax, Caspase-3, Caspase-9 in the model. Totally 15 Chinese experimental miniature swine were adopted and randomly divided into the control group, the model group and the phlegm and stasis-treating group. The model group and the stasis-treating group were fed with high fat diets for two weeks, intervened with the coronary artery injury and then given drugs and high fat diets for eight weeks. The control group was fed with ordinary diets for 10 weeks, without the coronary artery injury. After the experiment, myocardia at the juncture of infracted areas were collected and made into formalin-fixed paraffin sections. The TDT-mediate dUTP nick end labeling (TUNEL) assay was used to detect the myocardial apoptosis. The immunohistochemistry (IHC) technique was applied to detect Bcl-2, Bax, Caspase-3, Caspase-9 levels in myocardial tissues. According to the findings, the apoptosis indexes (AI) for the control group, the model group and the phlegm and stasis-treating group were 0.92%, 27.68%, 17.28%, respectively. The AI of the phlegm and stasis-treating group was significantly lower than that of the model group (P < 0.01). Compared with the model group, the phlegm and stasis-treating group showed significantly higher Bcl-2 protein expression (P < 0.01) and lower Bax, Caspase-3 and Caspase-9 protein expressions (P < 0.01). In conclusion, Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction have a significant protective effect against the myocardial apoptosis in miniature swine phlegm and blood stasis type coronary heart disease model.
Animals
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Apoptosis
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drug effects
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Caspases
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metabolism
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Coronary Disease
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drug therapy
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Disease Models, Animal
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Drug Therapy, Combination
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Drugs, Chinese Herbal
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administration & dosage
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Female
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Male
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Medicine, Chinese Traditional
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Myocardium
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pathology
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Phytotherapy
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Proto-Oncogene Proteins c-bcl-2
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analysis
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Swine
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Swine, Miniature
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bcl-2-Associated X Protein
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analysis
4.Emergency repair of severe complex defect in forearm by transplantation of free flap and functional reconstruction
Shu-Jian HOU ; Guo-Liang CHENG ; Guang-Rong FANG ; Zhen-Jun WANG ; Le-Tian SUN ; Xu HE ; Hong-Xun ZHANG ;
Chinese Journal of Microsurgery 2006;0(05):-
Objective To report the outcome of emergency repair of severe complex defect in forearm by transplantation of free flap and simultaneous functional reconstruction.Methods From Mar.1994 to Aug.2003,4 cases with severe complex defect in forearm was repaired by transplantation of free skin flap, free skin flap combined with fibula flap,or fibula osteocutaneous flap in emergency.Simultaneously the flexion and extension function were repaired by muscle transfer and/or tendon grafting,tenonectomy.Results All the cases were successful.Follow-up period ranged from 1 to 3 years postoperatively.The blood-supply,tex- ture and elasticity of transferred flaps were excellent with good bone healing.Opposition of thumb with four fin- gers was good.Sensory recovery of the hand was satisfactory.Conclusion Transplantation of free flap com- bined with simultaneous functional reconstruction is an ideal method in emergency repair of severe complex de- fect in forearm.
5.Tenidap is neuroprotective in a pilocarpine rat model of temporal lobe epilepsy.
Xing-Hua TANG ; Xun-Yi WU ; Lan XU ; You-Xin FANG ; Jian-Hong WANG ; Guo-Xing ZHU ; Zhen HONG
Chinese Medical Journal 2013;126(10):1900-1905
BACKGROUNDTenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE).
METHODSTenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death.
RESULTSThere were 46.88 ± 10.70 survival neurons in tenidap-SE group, while there were 27.60 ± 5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75 ± 8.78 survival neurons in tenidap-SE group, while there were 33.40 ± 8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P < 0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area.
CONCLUSIONTenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.
Animals ; Cyclooxygenase 2 ; metabolism ; Epilepsy, Temporal Lobe ; chemically induced ; drug therapy ; metabolism ; Indoles ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Pilocarpine ; toxicity ; Rats ; Rats, Wistar
6.Structural characterization of chlorobenzylidine.
Zhong-Hong LI ; Kun-Yi NI ; Guo-Xiong ZHOU ; Can ZHANG ; Wen-Long HUANG ; Si-Xun PENG
Acta Pharmaceutica Sinica 2004;39(7):546-550
AIMTo study the structure and crystal forms of chlorobenzylidine.
METHODSKarl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine.
RESULTSChlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms.
CONCLUSIONThe studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.
Benzylidene Compounds ; Crystallization ; Crystallography, X-Ray ; Differential Thermal Analysis ; Molecular Conformation ; Molecular Structure ; Polycyclic Compounds ; chemistry ; Stereoisomerism
7.Traditional Chinese medicine and formulas of improving peripheral nerve regeneration.
Shao-yin WEI ; Pei-xun ZHANG ; De-mei YANG ; Hong-bo ZHANG ; Bao-guo JIANG
China Journal of Chinese Materia Medica 2008;33(17):2069-2072
Peripheral nerve impairment is a common complication in surgery, which repair relates directly to the recovery of motor function and sensory function. Clinical researchers always do nerve sutrure using microsurgical technique and adjuvant treatment to improve peripheral nerve regeneration. Western medicine used usually of adjuvant drugs, such as neurotrophic factors, are limited by their defects in clinical application. Traditional Chinese medicine classifies peripheral nerve impair as paralysis and arthromyodynia, considers that it is the result of defects of meridian and vessels, QI and blood, bones and muscles. So, drugs used usually are QI invigorating herbs, blood circulation promoting herbs for unblocking collaterals, and nourishing herbs, including astragali, hedysari, ginkgo leaf, angelica, danshen root, paeoniae radix, epimedium, chuanxiong, and common basic formulas, such as Buyang Huanwu decoction, Huangqi Guizhi Wuwu decoction, Huoxue Kangyuan decoction, compound radix hedysari, etc. To be ready for further study and development, we review the traditional Chinese medicine and formulas in this article.
Animals
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Chemistry, Pharmaceutical
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Drugs, Chinese Herbal
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administration & dosage
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Humans
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Medicine, Chinese Traditional
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Nerve Regeneration
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drug effects
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Peripheral Nervous System Diseases
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drug therapy
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physiopathology
8.Expression of ezrin and CD44-v6 in human esophageal squamous cell carcinoma and its clinical significance.
Li-Xun CHAI ; Ke-Lin SUN ; Li-Ping GUO ; Hong-Tu ZHANG ; Shi-Xin LU
Chinese Journal of Oncology 2007;29(9):685-688
OBJECTIVETo evaluate the expression of ezrin and CD44-v6 in esophageal squamous cell carcinoma, and to evaluate its relationship with lymph node metastasis (LNM) and histological grading.
METHODSThe expression of ezrin and CD44-v6 in 71 patients with esophageal squamous cell carcinoma was studied using immunohistochemical (SP) method. The correlation of their expression with relevant clinical data was statistically analyzed.
RESULTSIn normal esophageal squamous epithelia, the expression of ezrin was found in 33 cases among 71 cases and the expression of CD44-v6 in 18 cases among 71 cases. In esophageal squamous cell carcinoma, the expression of ezrin was found in 64 cases among 71 cases and CD44-v6 in 58 cases among 71 cases. The expression of ezrin was closely related to LNM. The positive rate of ezrin expression in LNM cases was significantly higher than that in cases without LNM. The expression of CD44-v6 had a close relation to tumor differentiation and LNM. The positive rate of CD44-v6 expression in LNM cases was significantly higher than that in patients without LNM. The expression of ezrin in CD44-v6 positive cases was significantly higher than that of CD44-v6 negative cases. The LNM rate was 60.0% in 48 patients with positive expression of both ezrin and CD44-v6, while none of lymph node metastasis was found in the 6 patients with both negative.
CONCLUSIONThe test of CD44-v6 and ezrin expression may have significant prognostic value for assessing the degree of malignancy and potential LNM probability of ESCC. Ezrin may become a new target in evaluation of tumor prognosis.
Carcinoma, Squamous Cell ; metabolism ; pathology ; Cytoskeletal Proteins ; metabolism ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging
9.Studies on the alkaloids from stem of Artabotrys hainanensis.
Chang-ri HAN ; Guo-yuan ZHU ; Guang-ying CHEN ; Han-yang ZHANG ; He-ping BI ; Hong-xun FANG
China Journal of Chinese Materia Medica 2005;30(21):1660-1662
OBJECTIVETo investigate the alkaloids from the stem of Artabotrys hainanensis.
METHODCompounds in plant extracts were separated by silica gel and sephadex LH-20 column chromatography. Chemical structures were elucidated by chemical and spectral analyses including UV, 1H-NMR, 13C-NMR, ESIMS and ESI-MS-MS.
RESULTEight alkaloids were isolated and identified as spinosine (1), 3-hydroxynornuciferine (2), juzirine (3), artabotrine (4), liridine (5), assimilobine (6), isococlaurine (7), N-demethylarmepavine (8).
CONCLUSIONAll alkaloids were isolated from this plant for the first time and compounds 1, 3, 7 and 8 were isolated from genus Artabotrys for the first time.
Alkaloids ; chemistry ; isolation & purification ; Annonaceae ; chemistry ; Berberine Alkaloids ; chemistry ; isolation & purification ; Isoquinolines ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry
10.Protective effects of Shuangshen Ningxin capsule on miniature swine after myocardial ischemia by intervention.
Zhen YU ; Jian-xun LIU ; Xin-zhi LI ; Xiao-hong SHANG ; Ai-guo YAN ; Xin-qing FENG
China Journal of Chinese Materia Medica 2007;32(16):1695-1699
OBJECTIVETo study the therapeutical effects of Shuangshen Ningxin capsule on miniature swine after myocardial ischemia by intervention.
METHODMyocardial ischemic model miniature swine induced by self-thrombus via cardiac catheter in left anteriar descending coronary artery (LAD), were administrated Shuangshen Ningxin capsule for 6 days. The changes of coronary arteriography, hemodynamics, biochemistry and pathohistology were observed.
RESULT6 days after modeling, LAD in myocardial ischemic miniature swine was basically embolized, cardiac output (CO), cardiac index (CI), left cardiac work (LCW) and left cardiac work index (LCWI) obviously lowed, and pathohistological analysis revealed myocardial degeneration, necrosis, fibrosis and inflammatory cell infiltration. After being administered with shuangshen Ningxin capsule 6 days, the degree of self-thrombus blocked LAD reduced, hemodynamic indexes of CO, CI, LCW, LCWI and blood plasm superoxide dismutase (SOD) activity increased, and systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) and malondialdehyde (MDA) content were lowed. on the same time, pathohistological degeneration and necrosis reduced.
CONCLUSIONShuangshen Ningxin capsule has anti-myocardial ischemia effect by improving cardiac muscle systolic function, increasing left cardiac work, inhibiting cardiac muscle cellular membrane lipid peroxidation.
Animals ; Capsules ; Cardiac Output ; drug effects ; Cardiotonic Agents ; administration & dosage ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Female ; Hemodynamics ; drug effects ; Male ; Malondialdehyde ; blood ; Myocardial Contraction ; drug effects ; Myocardial Ischemia ; blood ; physiopathology ; prevention & control ; Myocardium ; pathology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry ; Superoxide Dismutase ; blood ; Swine ; Swine, Miniature ; Vascular Resistance ; drug effects