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.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
;
Apoptosis
;
drug effects
;
Caspases
;
metabolism
;
Coronary Disease
;
drug therapy
;
Disease Models, Animal
;
Drug Therapy, Combination
;
Drugs, Chinese Herbal
;
administration & dosage
;
Female
;
Male
;
Medicine, Chinese Traditional
;
Myocardium
;
pathology
;
Phytotherapy
;
Proto-Oncogene Proteins c-bcl-2
;
analysis
;
Swine
;
Swine, Miniature
;
bcl-2-Associated X Protein
;
analysis
3.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
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.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
;
Chemistry, Pharmaceutical
;
Drugs, Chinese Herbal
;
administration & dosage
;
Humans
;
Medicine, Chinese Traditional
;
Nerve Regeneration
;
drug effects
;
Peripheral Nervous System Diseases
;
drug therapy
;
physiopathology
7.Effect of G-CSF on murine thymocyte emigration and cell cycle alteration after a sublethal dose of irradiation.
Hong-Xia ZHAO ; Mei GUO ; Xue-Dong SUN ; Kai-Xun HU ; Hui-Sheng AI
Journal of Experimental Hematology 2011;19(5):1294-1298
This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy γ-ray total body irradiation and then randomly divided into G-CSF and control groups. Mice in the G-CSF group were injected recombinant human G-CSF 100 µg/(kg·d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 ± 5.0)% vs (75.9 ± 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 ± 4.8)% vs (15.7 ± 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 ± 2.4)% and (15.5 ± 3.3)%, respectively, which were significantly lower than that of the control group (16.5 ± 2.2)% and (22.6 ± 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation.
Animals
;
Cell Cycle
;
drug effects
;
radiation effects
;
Female
;
Gamma Rays
;
adverse effects
;
Granulocyte Colony-Stimulating Factor
;
pharmacology
;
Mice
;
Mice, Inbred BALB C
;
Recombinant Proteins
;
pharmacology
;
Thymocytes
;
drug effects
;
radiation effects
8.A new experimental model to study healing process of metaphyseal fracture.
Na HAN ; Pei-xun ZHANG ; Wei-bin WANG ; Da-cheng HAN ; Jian-hai CHEN ; Hong-bo ZHAN ; Bao-guo JIANG
Chinese Medical Journal 2012;125(4):676-679
BACKGROUNDThere are few researches for the healing of metaphyseal fractures; moreover, the animal models to study the metaphyseal fractures are usually made by the oscillating saw osteotomy without reliable fixation, which is not in accordance with our current clinical practice. In this study, we established a new model to observe the healing process of metaphyseal fractures.
METHODSEighteen New Zealand rabbits were used in the study. The fracture model was created by splitting the medial tibial plateau in rabbits, then reset, and fixed with compression screws. At 1, 2, 3, 4, 6, and 8 weeks postoperatively, the tibial specimens were collected; firstly, a general observation and an X-ray examination of the specimens was done, and then they were embedded in methylmethacrylate and cut into sections with hard tissue slicer. The sections were stained with Giemsa reagent and examined under light microscopy.
RESULTSThere was no fracture displacement in the tibial specimens of all time points, except for one showing a collapse. No external callus formation could be observed by X-ray and general examination. After 1 week of the operation, the fracture gap was filled by mesenchymal tissue; 2 weeks postoperatively, a large number of woven bones were formed; from the third week onwards, the woven bone began to turn into lamellar bone, and new trabecular structure began to form. In all of the slices, no obvious chondrocytes formed in fracture areas; thus, there was no endochondral ossification.
CONCLUSIONSThis model was an ideal fracture animal model and suitable for the study of metaphyseal fracture healing. The X-ray and histological images demonstrated that metaphyseal fracture healing was a process of direct bone healing through intramembranous bone formation under the conditions of minor trauma, good reduction, and firm fixation.
Animals ; Fracture Healing ; physiology ; Fractures, Bone ; diagnostic imaging ; pathology ; Rabbits ; Radiography
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.The prospective study project of 62 cases spinal cord injury.
Pei-Xun ZHANG ; Feng XUE ; Jing WANG ; Hong-Bo ZHANG ; Hai-Lin XU ; Bao-Guo JIANG
Chinese Journal of Surgery 2009;47(6):461-464
OBJECTIVETo rudiment analyze the different intervention factors affecting the spinal cord injury functional recovery initially through prospective study project.
METHODSDesigned prospective study project without clinical treatment intervention and admitted 62 spinal cord injury cases into observation group from Dec 2006 to Dec 2007. The internalized standard included acute spinal cord injury within 1 week, aged from 18 to 65 years old without sexuality difference and diagnosed as type A injury: total spinal cord injury or type B injury: non-total spinal cord injury (without movement function below the injury plane) according to clinical physical examination and combined MRI or CT examination. All the 62 cases were followed up. The spinal cord function were estimated at the time of arriving hospital, 1, 3, 6 months after injury during the following up time according to the American Spine Injury Association standard (Revised at 2000) and functional independence measure (FIM) score. The intervention factors affecting the spinal cord injury functional recovery were analyzed.
RESULTSAmong the 62 cases, male 60 cases and female 2 cases, aged from 18 to 41 years old, mean age 24 years old, 29 cases can be classified into type A injury and 33 cases can be classified into type B injury. There was no significant difference (Index including sense ASIA, motor ASIA and FIM) between operation group and non-operation group, namely conservatively composite treatment at all observation point in all type A injury cases (P > 0.05). There was significant difference (Index including sense ASIA, motor ASIA and FIM) between operation group and non-operation group at all observation point in all type B injury cases (P < 0.05); And there was significant difference (Index including sense ASIA, motor ASIA and FIM) between operated in 8 hours (< or = 8 h) group and beyond 8 hours (> 8 h) group at all observation point in all type B operated cases (P < 0.05).
CONCLUSIONSOperation and operation time were of no significant value for type A injury (total spinal cord injury), but considering the nursing convenience and the need for spinal stabilities, operation decompression and internal fixation can be chosen; Operation decompression should be performed as soon as quickly for type B injury (non-total spinal cord injury) in order to get better functional recovery.
Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Injury Severity Score ; Male ; Middle Aged ; Prospective Studies ; Recovery of Function ; Spinal Cord Injuries ; physiopathology ; surgery ; Treatment Outcome ; Young Adult