1.Mesenchymal stem cell transplantation for intracerebral hemorrhage
Fan XU ; Xinghua PAN ; Shixiang LIU
International Journal of Cerebrovascular Diseases 2009;17(1):24-28
The onset of intracerebral hemorrhage is often sudden arid dangerous with high mortality. At present, it lacks truly effective theraputic measures and medications. Mesenchy-mal stem cell has multilineage differentiation potential induced trader a specific micro-environment, and it can be successfully induced and differentiated into osteoblasts, cartilage cells, myocardial cells, neurons, glial cells, and so on under the different micro-environment conditions. It has brought a new hope for the treatment of intracerebral hemorrhage.
2.Effects of edaravone on the expression of TGF-β1 and myocardialfibrosis in rats
Shixiang WANG ; Hongchao WU ; Yingfeng LIU
Tianjin Medical Journal 2016;44(1):67-70
Objective To investigate the effects of edaravone on myocardial fibrosis induced by isoproterenol (ISO) in rats, and to discuss the correlation between the level of transforming growth factor-β1 (TGF-β1) and the myocardial fibrosis. Methods Forty male SD rats were randomly divided into five groups, namely control group, model group and edaravone groups (low, medium and high doses). Isoproterenol was used to establish the rat model of myocardial fibrosis. Edaravone groups were given edaravone [3, 5 and 10 mg/(kg · d)] to intervene for 14 days. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were examined after 15-d treatment. The left ventricular mass index (LVMI) and collagen volume fraction (CVF) were examined. The expression of TGF-β1 was detected by Western blot assay and immuno-fluorescence method. Results The content of MDA and LVMI were significantly higher in model group than those of the control group (P<0.01),whereas the content of SOD was significantly lower in model group than that of the control group (P<0.01). Compared with model group, the expression level of MDA decreased with the increased intervention dose of edara-vone (P<0.05), while SOD expression level increased (P<0.05). There was no significant difference in the level of SOD be-tween middle dose edaravone group and the control group. LVMI was decreased with the increased doses of edaravone ( P<0.01). There was no significant difference in LVMI between the high dose of edaravone group and the control group. Com-pared with the control group, the expression level of TGF-β1 was significantly increased in model group (P<0.01). The ex-pression level of TGF-β1 was reduced with the increased doses of edaravone. CVF was significantly increased in model group compared with that of control group (P<0.001). CVF decreased with the increased doses of edaravone in medium and high doses of edaravone groups, but they were higher than that of control group (P<0.01). TGF-β1 was positively correlated with MDA, LVMI and CVF (r=0.931, 0.879 and 0.930, P<0.001). SOD was negatively correlated with TGF-β1 (r=-0.892, P<0.001). Conclusion Edaravone can relieve myocardial fibrosis by inhibiting oxidative stress and TGF-β1 in rats.
3.Pathophysiology of Cerebral Hemorrhage and Hematoma Enlargement (review)
Jianxin ZHENG ; Qiang LI ; Shixiang LIU
Chinese Journal of Rehabilitation Theory and Practice 2007;13(11):1034-1036
It is important to investigations of early course and pathophysiologic mechanism of cerebral hemorrhage for drawing therapy and prognosis.This paper would review the formation and enlargement of hematoma after bleeding.
4.Clinical study of brain post-traumatic syndrome and heavy cerebral trauma with hemorheology and transcranial Doppler
Shixiang LIU ; Bo LIU ; Yan LIANG ; Wenfu WANG
Chinese Journal of Rehabilitation Theory and Practice 2005;11(5):386-387
ObjectiveTo study the change of cerebral blood flow and hemorheology in patients with brain post-traumatic syndrome (PTS) and heavy cerebral trauma.Methods122 cases(A group) of PTS and 113 cases(B group) of heavy cerebral trauma were explored the anterior cerebral artery (ACA),middle cerebral artery (MCA),posterior cerebral artery (PCA),vertebral artery (VA) and basilar artery (BA) with transcranial Doppler (TCD). Their blood viscosity, plasm viscosity, red blood cell (RBC) deformed exponent were also measured.ResultsThe blood stream in most of patients with PTS manifested slowing especially in MCA,ACA,VA and BA at left. However,most of patients with heavy cerebral trauma manifested vasospasm. The blood and plasm viscosity of both groups obviously increased, but RBC deformed exponent decreased.ConclusionPatients with PTS suffered organic brain damage, mainly in levo-hemisphere.The patients with PTS or with heavy cerebral trauma present disorder in hemorheology.
5.Effect of brain-derived neurotrophic factor on environmental nutrition and neural differentiation of the transplanted stem cells under hypothermia
Sai ZHANG ; Xiaozhi LIU ; Hongtao SUN ; Yue TU ; Shixiang CHENG
Chinese Journal of Trauma 2011;27(1):68-71
Objective To study the effect of brain-derived neurotrophic factor (BDNF) on the environmental nutrition and neural differentiation of the transplanted stem cells under hypothermia.Methods The BDNF gene mediated by liposome was transfected into 293T cell line, and ELISA assay was applied to find the peak time of BDNF expression. When BDNF was highly expressed, the supernatant was collected for establishment of SD rat models of brain injury. The rats were divided into Group A (stem cell transplantation group) and Group B (stem cell transplantation and BDNF group). Rats in both groups were under hypothermia treatment for five days. Four and eight days later ( three days from rewarming), rat brain tissues were obtained to detect the expressions of proliferating cell nuclear antigen (PCNA), nestin, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) by immunohistochemical method and to detect the apoptosis by in situ hybridization. Finally, the nerve function scores were obtained for evaluation of the nerve function. Results The ELISA showed that the high level of BDNF expression was at 48 to 60 hours after gene transfection. PCNA and nestin were highly expressed, while NES and GFAP showed nil or low level of expression in both groups at the fourth day after hypothermia, with little apoptotic cells especially in the Group B (P <0.05). The expressions of PCNA and nestin were decreased, but the expressions of NSE and GFAP were increased at the third day after rewarming. The positive rate of NSE expression in the Group B was much higher and the apoptotic cells were much less compared with the Group A ( P < 0. 05 ). A better nerve score was obtained in the Group B. Conclusion BDNF can enhance the survival rate of the transplanted stem cells and induce their differentiation into neurons under hypothermia.
6.Expression of 11β-hydroxysteroid dehydrogenase type 1 on hippocampus of rat with chronic unpredictable mild stress
Shixiang CHENG ; Yue TU ; Sai ZHANG ; Li WEN ; Xiaozhi LIU
Chinese Journal of Behavioral Medicine and Brain Science 2012;21(7):634-637
ObjectiveTo investigate the roles of 11 β-hydroxysteroid dehydrogenase type 1 ( 11 β-HSD1 )on hippocampus of rat with chronic unpredictable mild stress (CUMS).MethodsTwenty-four male SpragueDawley rats were randomly divided into control group and depressive model group. Chronic unpredictable mild stress (CUMS) was used to make up depressive animal model.Behavioral changes were recorded by body weight measuring,sucrose consumption test (SCT) and open field test (OFT),respectively.The mRNA transcription of 11β-HSD1 in hippocampus tissues of the rats were detected by real-time RT-PCR,and the protein expression of 11β-HSD1 were detected by western blot and immunofluorescence.ResultsBcforc starting CUMS protocol,the rats exhibited equivalent weight and sucrose consumption.Twenty-eight days after CUMS protocol,behavior parameters such as body weight,sucrose consumption,nunber of crossing,and number of rearing were significantly decreased in rats exposed to CUMS group compared with control group (P < 0.05,P < 0.01 ).Correspondingly,realtime RT-PCR assays showed the mRNA expression of 11 β-HSD1 in the hippocampus of CUMS group,which was (31 ±9) % lower than that of control group.Meanwhile,the protein expression of it in CUMS group was lower than that of control group (P < 0.05 ).Inmunofluorescence revealed that the number of positive 11 3-HSD1 cells was high (223 ± 13) in the control group,while the number was decreased prominently (92 ± 11 ) in the CUMS group (P < 0.01 ).ConclusionDepressive behavior of rats is induced and the expression of 11 β-HSD1 in the hippocampus is decreased prominently by CUMS,the mechanism of which is at least related to the low expression of 11β-HSD1 and disturbance of glucocorticoid metabolism caused by CUMS.
7.Pharmacokinetics of gastrodigenin in brain tissue of mice after intragastric administration of gastrodin
Zheng CAI ; Shixiang HOU ; Zhongqiu LIU ; Qiuhong CHEN ; Zhaoxiang YANG
Chinese Traditional and Herbal Drugs 1994;0(03):-
Objective To establish an HPLC method for determination of gastrodigenin concentration in brain tissue of mice and investigate its pharmacokinetics after intragastric administration of gastrodin.Methods The brain homogenate was extracted with acetoacetate and analyzed by HPLC method.The separation was performed on a Diamonsil C18 column(250 mm ? 4.6 mm,5 ?m) under the following chromatographic conditions: mobile phase,acetonitrile-water(10.5∶89.5);column temperature,25 ℃;flow rate,1.0 mL/min;detection wavelength,221 nm;and sampling amount,20 ?L.Results The calibration curve showed good linearity within the concentration range of 50-1 616 ng/mL(r= 0.999 6).The relative recoveries were 93.8%-95.1%,and the RSDs of the intra-and inter-day precision were less than 10%.The concentration-time profile of gastrodigenin in brain tissue of mice showed double peaks(tmax1=15 min,tmax2=90 min).The AUC was 52 822.5 ng?min/g,and t1/2(ke) was 54.8 min.Conclusion The analytical method established for assay of gastrodigenin in brain tissue of mice is sensitive and accurate.The result indicates that gastrodin could rapidly distribute to the brain,be metabolized into gastrodigenin,and be eliminated after oral administration.
9.Influence of aspirin on nerve injury of experimental cerebral ischemia in rabbits
Shixiang LIU ; Jingbian HOU ; Qingzhou YANG ; Jialin ZHANG ; Lichun HUANG
Chinese Journal of Pathophysiology 1986;0(02):-
Platelet play an important role in cerebral ischemial nerve injury. Aspirin (ASA) had been used to treat and prevent stroke in clinic. 30 rabbits were randomly divided into A, B and C groups. In group A ASA was given orally at a daily dosage of 15 mg/kg per rabbit for 5 days before cerebral ischemia; group B cerebral ischemia without giving ASA, and group C was normal rabbits as controls. The cerebral ischemial model was produced by occluding bilateral carotid arteries and bleeding from femoral artery. The results indicated that there was an obvious decrease of PAgT and TXA_2 and had no significance changes in free radicals increasing and Ca~(2+) rising from cerebral tissue in group A. The cerebral edema of group A was less severe than group B. It seemed that ASA had a protective effect on the nerve injury of cerebral ischemia. The derangement of ASA, platelet, free radicals and calcium ions interrelation and their significance on the nerve injury should be further studied.
10.Pharmacokinetics and Pharmacodynamics of Intravenous Famotidine in Healthy Volunteers
Gaolin LIU ; Shen GAO ; Shixiang WANG ; Guoming XU
Academic Journal of Second Military Medical University 1981;0(04):-
The pharmacokinetics and pharmacodynamics of famotidine were investigated in 10 healthy male volunteers after single intravenous administration of 20 mg. The blood drug levels were determined by a high performance liquid chromatography. The 1gC of famotidine in plasma vs time curve were found to be twcncompartment open model in healthy volunteers. The terminal half-life averaged 3.16h; the total distribution volume 99.40L; the total plasma clearance 392.12ml/min; the area under the plasma concentration curve 1057.45 h?ng/ml. A mathematic equation describing the whole course of blood drug levels in relation to inhibitory effects on intragastric acid output is as follows: E= 100?C2.60/(C2.60+14.712.60). The constant 14.71 is EC50 (ng/ml), the blood drug concentration producing 50% of maximal pharmacological effects. Prediction of pharmacodynamic effects from blood drug level and vice versa becomes possible by using the mathematic equation.