Hypoxic-ischemic Brain Damage Group Research Articles

Changes of plasma corticotrophin releasing factor levels in the young rats with hypoxic-ischemic brain damage

Objective To explore the changes of plasma corticotrophin releasing factor (CRF) levels in the young rats with hypoxic-ischemic brain damage.Methods Two hundred and forty young rats were randomly divided into three groups:hypoxic-ischemic brain damage group ( model group,n =80),sham-operated group ( n =80),and normal control group ( n =80).The plasma CRF levels of rats in three groups were detected at 1 h,3 h,6 h,12 h,l d,3 d,5 d and 18 d after hypoxia-ischemia,per ten rats for each time point.Plasma CRF levels were measured by radioimmunoassay.Results Plasma CRF levels of model group,shamoperated group and normal control group showed no significant difference in the young rats after 1 h,3 h,6 h,12 h of hypoxia-ischemia ( P ＞ 0.05 ).But plasma CRF levels in the model group were respectively significantly lower than those of sham-operated group and normal control group after 1 d and 3 d of hypoxia-ischemia ( P ＜0.001 ),and then recovered to the control group levels after 5 d and 18 d of hypoxia-ischemia ( P ＞0.05 ).Conclusion Hypoxia-ischemia affects plasma CRF levels in the young rats,which is related with the duration after hypoxia-ischemia. Key words: Hypoxic-ischemic brain damage; Corticotrophin releasing factor; Rat

Tanshinone IIa Alleviates the Biochemical Changes Associated with Hypoxic Ischemic Brain Damage in a Rat Model

This study aimed to investigate the effects of Tanshinone IIa (TanIIa) on the biochemical changes associated with hypoxic ischemic brain damage (HIBD) in a rat model. Neonatal SD rats were randomized into normal control, HIBD and TanIIa + HIBD groups. At different time points after HIBD, TanIIa was given at 1 µg/g. The intracellular free calcium concentration and the expression of phospho-NR1 S897 was determined. The intracellular free calcium concentration in the HIBD group was significantly increased. The induction of intracellular free calcium concentration in the TanIIa + HIBD group was less than that in the HIBD group. Large amounts of phospho-NR1 S897 positive cells were distributed in the cortex in the normal control group; the number of phospho-NR1 S897 positive cells in the ipsilateral cortex was dramatically decreased at 24 h after HIBD. Both the number of phospho-NR1 S897 positive cells and the FITC fluorescent density in the HIBD + TanIIa group were less than those in the normal control group at every time point after HIBD, but more than those in the HIBD group. TanIIa alleviated the down-regulation of phospho-NR1 S897 and the elevated intracellular free calcium concentration in the cerebral cortex in the HIBD model. TanIIa could exert a neuroprotective effect through affecting NMDA receptor expression, inhibiting calcium transportation and decreasing the intracellular free calcium concentration.

Neuroprotective effects of NEP1-40 and fasudil on Nogo-A expression in neonatal rats with hypoxic-ischemic brain damage

The hypoxic-ischemic encephalopathy caused by peripartum asphyxia is a serious disease in newborn infants, and effective therapies need to be developed to reduce injury-related disorders. We evaluated the effects of NEP1-40 and fasudil on Nogo-A expression in neonatal hypoxic-ischemic brain damage (HIBD) rats. Seven-day-old Wistar rats were randomly divided into control, HIBD, NEP1-40, and fasudil groups. NEP1-40 and fasudil groups were injected intraperitoneally with these compounds. Rat brains at 6, 24, 72 h, and 7 days after HIBD were collected to determine histopathological damage and the expression levels of Nogo-A. Histopathological damage was reduced in NEP1-40 and fasudil groups compared with the untreated HIBD group. The expression of Nogo-A in the HIBD group was significantly higher than that in control, NEP1-40 and fasudil groups at the same times. Compared with the fasudil group, the expression levels of Nogo-A were significantly reduced in the NEP1-40 group. We conclude that NPE1-40 and fasudil have potential for neuroprotective effects in the neonatal rat HIBD model, mediated by inhibiting Nogo-A/ Rho pathways.

Effect of Tanshinone IIA on phosphorylated NMDA receptor 1 expression and intracellular free calcium concentration in neonatal SD rats with hypoxic ischemic brain damage

To determine the effect of Tanshinone IIA (TanIIA) on the phosphory-lated NMDA receptor 1 at Serine 897 site (phospho-NR1 S897) and intracellular free calcium concentration ([Ca(2+)](i)) in neonatal SD rats with hypoxic ischemic brain damage (HIBD), and to explore the neuroprotective mechanism of TanIIA in HIBD. Neonatal SD rats were randomly divided into a normal control, and an HIBD and TanIIA+HIBD group. Rice-Vannucci method was used for HIBD animal model. Time points were: 3, 6, 12, and 24 h after HIBD (n=10 in each group at each time point). TanIIA was intraperitoneally given at 1 μg/g every 12 h. Fura-2AM was used to mark the fluorescent calcium probe and [Ca(2+)](i) was measured by a Hitachi F-4500 Fluorescence Spectrophometer. Fluorescent immunohisotichemical study was used for the expression of phospho-NR1 S897. (1) Compared with the normal control group, both the [Ca(2+)](i) absolute number and ipsi-/contra-lateral ratio were increased at each time point with statistical significance (P<0.05). Compared with the HIBD group, the [Ca(2+)](i) in the HIBD+ TanIIA group was decreased at each time point. At 24 h after HIBD, the ipsi-/contra-lateral ratio of HIBD+ TanIIA group was 24.9% less than that of HIBD group with statistical significance (P<0.05). (2) In the normal control group, abundant phospho-NR1 S897 positive cells were nicely distributed in the cortex. Compared with the normal control group, at each time point, both the absolute number of phospho-NR1 S897 positive cells and the fluorescent intensity of phospho-NR1 S897 in the ipsilateral cortex of the HIBD group were decreased with statistical significance (P<0.05). Compared with the HIBD group, both the absolute number of phospho-NR1 S897 positive cells and the fluorescent intensity of phospho-NR1 S897 in the ipsilateral cortex of HIBD+ TanIIA were increased. There was significant difference at 3 and 12 h after the HIBD (P<0.05). TanIIA reduced the HIBD-caused down-regulation of phospho-NR1 S897 and the HIBD-caused [Ca(2+)](i) elevation in the cortex. The neuroprotective effect of TanIIA may be related to influencing NMDA receptor expression and decreasing intracellular free calcium aggregation.

Expressions of matrix metalloproteinase-9 (MMP-9) and occludin in brain tissue of hypoxic-ischemic neonatal rats

Objective To investigate the effect of MMP-9 mRNA and occludin mRNA expressions after hypoxic-ischemic brain damage( HIBD). Methods Neonatal 7-day-old Sprague Dawley rats were ran-domly divided into control group,HIBD 3 h,6 h,24 h,48 h and 72 h groups (n =6 per group). The ligated cerebral hemisphere was observed for the morphological changes. The expression of MMP-9 mRNA and oc-cludin mRNA were measured by Real-time Q-PCR. Results (1)The ligated cerebral hemisphere of neonatal rats showed obvious edema from 24 h to 48 h after hypoxia-ischemia. (2) As compared to HIBD groups,the expression of MMP-9 mRNA was lower in control group (0. 7933 ± 0.0859) (P＜ 0.05). In the group of HIBD,it began to increase at 3h(l.1533 ±0.1291) ,and peaked at 24 h(3.4883 ±0.1759) .maintained the high level at 72 h(1.625 0±0. 1157). (3) The expression of occludin mRNA was higher in the control group(2.1780 ±0.0773) (P＜0.05), while in the group of HIBD, it began to decrease at 3 h(1.718 6 ± 0.1168) ,was lowest at 24 h(0.9066 ±0.0602) ,and maintained the low level at 72 h( 1.5966 ±0.0799). (4) The expression of MMP-9 mRNA negatively correlated with the expression of occludin mRNA (r = -0.815, P ＜0.05). Conclusion The increased expression of MMP-9 mRNA and the decreased expression of occlu-din mRNA after HIBD may play a role in the pathogenesis of HIBD in neonatal rats. Key words: Hypoxic-ischemia, brain; Matrix metalloproteinase-9; Tight junction protein; Occludin; Neonatal rats

Protective effect of intracerebral transplantation of human mesenchymal stem cells on hypoxic-ischemic brain damage in rats

Objective:To explore the migration,differentiation and the therapeutic effect of intracerebral transplantation of human mesenchymal stem cells (hMSCs) after hypoxic-ischemic brain damage in rats,and to test whether three anti-hMSCs monoclonal antibodies prepared by our group can detect hMSCs in rat brains.Methods: hMSCs were isolated and purified by density gradient centrifugation and adherence to culture flask.Cells of passage 3-5 were prelabeled with bromodeoxyuridine (BrdU) for 72 h before transplantation.Animal models of hypoxic-ischemic brain damage (HIBD) were built with 1 month old Wistar rats.Three days after hypoxia-ischemia,HIBD rats in hMSCs-treated group (n=18) received intracerebral transplantation of 5×105 hMSCs.In control group (n=18) HIBD rats received phosphate buffered saline of the same volume.In sham-operated group (n=6) and HIBD group (n=6),rats did not receive any transplantation.Rats in hMSCs-treated group and control group were allowed to survive for 0 day,3 days,1 weeks,2 weeks (all n=3) and 4 weeks (n=6,after transplantation). Rats in sham-operated group and HIBD group were allowed to survive for 31 days (4 weeks after transplantation).Rats of all the 4 groups received behavior test (alternative electro-stimulus Y-maze) 4 weeks after transplantation before sacrificed;their brains were sectioned for H-E staining.The brains from all rats were also prepared for immunohistochemistry analysis to detect the distribution of hMSCs.Results: Immunohistochemistry results showed that hMSCs migrated mainly along the ventricular system 1 week later,and a few hMSCs migrated along the corpus callosum to the opposite side.Four weeks after transplantaion,hMSCs migrated to the parenchyma and distributed throughout the cerebra.Behavior test showed that the total errors (TE) in hMSCs-treated group (TE= 5.00±2.82) were significantly less than those in the control group (TE=12.67±3.72,P0.05).H-E staining showed that the brain damage in the hMSCs-treated group was slighter than that of the control group and HIBD group.Conclusion: After transplanted in the brain of rats,hMSCs can survive and migrate in the central nervous system (CNS).hMSCs can promote tissue repair and functional recovery of rat brain,suggesting that hMSCs might be a possible treatment for hypoxic-ischemic brain damage.

Influence of mouse nerve growth factor on gliai fibrillary acidic protein expression in hippocampus of neonatal rats with hypoxic-ischemic brain damage

Objective To investigate the influence of mouse nerve growth factor (mNGF)on glial fibrillary acidic protein (GFAP) expression in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Sixty neonatal rats of 7 days old were randomly divided into control group (n=20) ,HIBD group (n=20) and mNGF group (n=20). After HIBD model established, mNGF of 20 ng/(g·d) was given by intramuscular injection in buttocks in mNGF group,continued five days. No intervention was given in HIBD group. 0.1mol/L PBS of 10 μ1/(g·d) was given by intramuscular injection in buttocks for the control group,continued five days. Ten rats were sacrified at 7 d and 14 d after intervention respectively in three groups, The expressions of GFAP in hippocampus were determined with immunohistochemical method. Results At 7 d and 14 d after intervention,the expression levels of GFAP in sick side hippocampous in HIBD group and mNGF group were higher than that in control group. GFAP positive cell mainly distributed in sick side hippocampal DG region in mNGF group, while CAI region in HIBD group. As compared with 7 d, the expression of GFAP in sick side hippocampus in HIBD group decreased at 14 d, while increased in mNGF group. Conclusion mNGF can increase the expression of GFAP in hippocampus of HIBD neonatal rat, and mNGF may have nervous repairing role to HIBD. Key words: Hypoxic-ischemic brain damage; Nerve growth factor; Glial fibrillary acidic protein; Neonatal rat

The expression changes of MMP-9 and TIMP-1 in the brain of neonatal rats with hypoxic-ischemic brain damage(HIBD)

Objective To explore the mechanism of hypoxic-ischemic brain damage(HIBD) and provide new ideas for clinical treatment of hypoxic-iscbemic encephalopathy.Methods Neonatal 7-day-old Wistar rats were randomly divided into sham-operation control group,HIBD 6 h,12 h,24 h,48 h and 72 h groups(n =6 per group).The model of HIBD was induced by unilateral carotid ligation followed by timed exposure to 8% oxygen.The expression of MMP-9 mRNA and TIMP-1 mRNA in brain tissue of neonatal rats was measured by Real-time Q-PCR method.Results (1) The ligatod brainhemisphere of HIBD groups showed obvious edema from 12 h to 48 h after hypoxia -ischemia in the neonatal rats.(2) The expression of MMP-9 mRNA was very low in the sham-operation control group,but in HIBD groups,it began to increase at 6 h,and reached a peak at 24 h,then gradually decreased,but still maintained at high level at 72 h(P＜0.01).(3) The expression of TIMP-1 mRNA was aslo very low in the sham-operation control group.But in HIBD group,it increased slightly at 6 h,12 h and 24 h,compared to the sham-operation control group,each group was statistically significant(P＜0.05),with no significant difference among the three groups(P＞0.05),then decreased at 48 h and 72 h,but with no significant difference from sham-operation control group (P＞ 0.05).(4) The ratio of MMP-9 mRNA/TIMP-1 mRNA was normal in the sham-operation control group and HIBD 6 h group,it began to increase at 12 h,and reached a peak at 48 h,then gradually decreased,but still maintained at high level at 72 h(P ＜0.01).Conclusion Hypoxia-ischemia increases the expression of MMP-9 mRNA in brain tissue of nenatal rats,and the imbalance in the expression of MMP-9 mRNA and TIMP-1 mRNA possibly is one cause of brain edema induced by HIBD. Key words: Cerebral hypoxia; Cerebral ischemia; Neonatal rats; MMP-9; TIMP-1

Adenovirus-mediated vascular endothelial growth factor165 gene therapy in treatment of hypoxic-ischemic brain damage: experiment with rats

To investigate the therapeutical effect of adenovirus-mediated vascular endothelial growth factor (VEGF)165 gene transplantation in treatment of hypoxic-ischemic brain damage. Recombinant vector of adenovirus-mediated VEGF165 gene (Ad-VEGF) was constructed by bacterial homologous recombination technology. Sixty 7-day-old Sprague-Dawley rats were randomly divided into 3 equal groups: hypoxic-ischemic brain damage (HIBD) group undergoing ligation of the left common carotid artery and inhalation of 8% oxygen for 2 hours, Ad-VEGF group undergoing injection of Ad-VEGF into the left sensorimotor cortex with the help of stereo-positioner 3 days after hypoxia-ischemia (HI), and sham operation group. Seven days after transplantation, 5 rats from each group were killed with their left brains taken out. The VEGF protein expression was detected by immunohistochemistry, and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). Since the age of 28 days T-maze foraging test was conducted. At the age of 34 days, sensorimotor tests were performed. After the behavioral tests all the rats were killed. The number of neurons in the CA1 region of the hippocampus and cerebral cortex was detected by Nissl's staining. Immunohistochemistry showed that the density levels of VEGF positive cells in cerebral cortex and hippocampus of the Ad-VEGF group were (68.09 +/- 3.37) and (68.37 +/- 3.17) respectively, both significantly higher than those of the HIBD group [(24.65 +/- 3.14) and (25.14 +/- 1.86) respectively, both P < 0.05]. TUNEL showed that the number of apoptotic neurons of the Ad-VEGF group was (151.4 +/- 21.7), significantly lower than that of the HIBD group [(264.4 +/- 16.3), P < 0.05]. Behavioral tests showed the percentages of accuracy on day 4 of the Ad-VEGF and sham operation groups were both significantly higher than that of the HIBD group (both P < 0.01). Nissl's staining showed that the numbers of neurons per unit area in the hippocampal CA1 area and cortex of the Ad-VEGF group were (70.6 +/- 2.3) and (95.1 +/- 2.8) respectively, both significantly higher than those of the HI group [(55.3 +/- 2.1) and (70.1 +/- 2.7) respectively, both P < 0.05]. Adenovirus vector-mediated VEGF gene therapy increases the VEGF protein expression, decreases neuron apoptosis, improves the long-term behavioral function after brain damage, and reduces hypoxic ischemic brain injury, thus possessing neuroprotective effects.

Study on the Therapic Effect of Intracerebral Transplantation of Human Mesenchymal Stem Cells in Rats with Hypoxic-Ischemic Brain Damage.

Objective: Recently, neural differentiation of mesenchymals stem cells (MSCs) provokes extensive interest. However, reports on the application of MSCs in hypoxic-ischemic induced diffuse neuronal degeneration disease are few research about the biological behavior of human derived MSCs (hMSCs) in vivo. Since heterogeneic MSCs could survive in vivo for long-term without significant immunological rejection, this study was designed to explore the migration, differentiation and the therapeutic benefit of hMSCs after hypoxic-ischemic brain damage (HIBD) in rats.Methods: Passage 3~5 hMSCs were prelabeled with bromodeoxyuridine (BrdU) for 72h before transplantation. Animal models of HIBD were built in one month old Wistar rats according to the method described by Rice. Three days after hypoxia-ischemia, HIBD rats in hMSCs-treated group (n=18) received intracerebral transplantation of 5×105 hMSCs, while HIBD rats received PBS of the same volume in control group (n=18). In sham-operated group (n=6) and only HIBD group (n=6), rats did not receive any transplantation. All of the groups did not received any immunosuppression agents. Rats of each group received behavior test (alternative electro-stimulus Y-maze) by single blind method, then were sacrificed and brains were sectioned for haematoxylin and eosin (HE) staining at 4 weeks post-transplantation. Rats in hMSCs-treated group and control group were killed on the date of 0 day, 3 days, 1 weeks, 2 weeks and 4 weeks post-transplantation while rats in sham-operated group and only HIBD group were allowed to survive for 4 weeks. The brains of all rats were anatomized and prepared for immunohistochemistry analysis with antibodies of BrdU, Nestin, Neurofilament (NF-M) and glial fibrillary acid protein (GFAP).Results: HIBD model were built successfully. Behavior tests (alternative electro-stimulus Y-maze) showed that the total errors (TE) in hMSCs-treated group (TE=5.0±2.82) were significantly less than those in the control group (TE=12.67±3.72) (p<0.05). HE straining indicated that the damage had lager pathological changes with bulks of neural cells necrosis and neuropil cavitations formation in cortex and hippocampus, however, it would be significantly improved in pathology in hMSCs-treated group. With the labeling rate of 51% in hMSCs by BrdU, hMSCs migrated mainly along the ventricular system, a few of which could migrate along the corpus callosum to the opposite side during one week post-transplantation. Four weeks later, hMSCs were observed to migrate to the parenchyma and distribute throughout the cerebra. Some hMSCs expressed GFAP in the local area of transplantation at three days post-transplantation, and a few of cells expressed NF near blood vessel. Nestin positive cells did not be detected at any time point. Four weeks after transplantation, BrdU and GFAP co-express cells increased which mainly distributed in the local area of transplantation, the cortex, hippocampus and ependymal layer.Conclusion: hMSCs could survive in the central nervous system of rats for at lest 4 weeks without any immunosuppression, moreover, hMSCs could migrate to the lesion area, express NF and GFAP which indicated their differentiation into mature neurons and neurogliocytes, and promote tissue repair and functional recovery of HIBD. Overall, the results suggested that hMSCs could be a promising treatment for HIBD.

Optimal therapeutic window of hyperbaric oxygenation in neonatal rat with hypoxic-ischemic brain damage

Hyperbaric oxygenation (HBO) is an attractive procedure that has been used in treatment of hypoxic-ischemic encephalopathy (HIE). However, depending on the HBO protocol, especially the time point of starting treatment of HBO, different and conflicting results were obtained. This study was undertaken to search for the optimal therapeutic window of ABO in neonatal rat with hypoxic-ischemic brain damage (HIBD). Eighty-four healthy seven-day-old SD rats were used as research subjects and were randomly divided into seven groups with 12 in each: sham group, HI group, HI (1 h) + HBO group (HBO starting 1 h after HI), HI (3 h) + HBO group (HBO starting 3 h after HI), HI (6 h) + HBO group (HBO starting 6 h after HI), HI (12 h) + HBO group (HBO starting 12 h after HI), HI (24 h) + HBO group (HBO starting 24 h after HI). Single HBO treatment (2.5 atmospheres absolute, ATA for 1.5 h) was used in this study. Two indexes were used to assess the effect of HBO that included short-term (48 h after HI) histology change (the cell density in CA1 of hippocampus and cortex) and long-term (5 w and 6 w after HI) neurobehavioral testing (grip test and treadmill test for evaluating the deficits of sensor motor; step-down avoidance test for assessing the deficits of memory). In HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups, neuron density of cortex and CA1 of hippocampus were 1981.76 +/- 299.55, 1841.53 +/- 241.21, 1525.78 +/- 189.00 and 4430.56 +/- 1180.31, 4507.54 +/- 1374.32, 3883.48 +/- 821.87, respectively, which were significantly higher than HIBD group (987.86 +/- 285.39 and 1813.59 +/- 295.33, P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO, the neuron density of cortex and CA1 of hippocampus compared with those in HIBD group had no statistical significance (P > 0.05, ANOVA). In the sensor motor testing performed at 5 w after HI of rat, the grip time in grip test and the stay time in treadmill test of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups were 193.39 +/- 51.19, 168.39 +/- 34.02, 168.95 +/- 34.93 and 130.34 +/- 42.56, 128.20 +/- 27.69, 125.74 +/- 36.99, respectively, which, compared with HIBD group, were significantly prolonged (P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO groups, the time was not significantly longer compared with HI (P > 0.05, ANOVA). In the step-down avoidance test which was performed at 6 w after HI, the step-down latencies of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO were 96.91 +/- 29.91, 90.35 +/- 28.44 and 76.46 +/- 38.70, respectively, which were significantly prolonged (P < 0.05, ANOVA), but in HI (12 h) + HBO and HI (24 h) + HBO, the latencies did not significantly increase compared with HIBD, P > 0.05, ANOVA. The optimal therapeutic window of HBO in neonatal rat with HIBD was within the first 6 hours after HI. In this therapeutic window, HBO was highly effective in reducing the cell loss in CA1 of hippocampus and cortex.

Effects of Simvastatin on the Expression of Intercellular Adhesion Molecule-1 mRNA in Neonatal Brain with Hypoxic-Ischemic Damage

The goal of this paper is to report on the study of the mechanism of neural damage in neonatal cerebral cortex and hippocampus when hypoxic-ischemic brain damage (HIBD) occurs and the neural protective effects of simvastatin. One hundred forty-four 7-day-old SD rats of were randomly divided into four groups, i.e., sham operation group (sham group), normal saline control group (HIBD group), citicoline control group (CDPC group), and simvastatin-treated group. Each group was divided into six time points (0 h, 12 h, 24 h, 48 h, 72 h, and 7 days after HIBD or sham operation), and each time point included six rats. The expression of intercellular adhesion molecule-1 (ICAM-1) mRNA was determined semiquantitively by reverse transcription polymerase chain reaction (RT-PCR) in the cortex and hippocampus of neonatal rats at different times to determine the differences. The expression of ICAM-1 mRNA rose obviously 12 h after HIBD in the ischemic hemisphere, peaked at 24 h, and then decreased gradually. There was a remarkably lower expression in the CDPC group and simvastatin group compared with the HIBD group at 12 h, 24 h, 48 h, and 72 h. At 7 days, there was no significant difference between the simvastatin group and the sham group (P > 0.05), and at 72 h, simvastatin down-regulated the expression of ICAM-1 mRNA in cortex significantly more than did citicoline (P < 0.05). Both simvastatin and CDPC can relieve the damages of the brain in rats with HIBD. The protective mechanisms of simvastatin and citicoline are associated with their regulative effect on ICAM-1, and simvastatin is superior to citicoline.

The protective mechanism of insulin-like growth factor-1 from hypoxic-ischemic brain damage in neonatal rats

目的 建立单侧缺氧缺血性脑损伤(HIBD)动物模型,研究胰岛素样生长因子1(IGF 1)对HIBD的影响和可能机制. 方法选择健康7日龄Wistar大鼠120只,建立HIBD模型,随机分成假手术组、HIBD组、HIBD后0.2 mg/kg人基因重组IGF-1干预组(RH-IGF-1组)、0.066mg/kg人基因重组IGF-1干预组(SRH-IGF-1组)及盐水对照组(对照组).各组按观察时段进一步分为24、48、72 h组,每组8只.各组于规定时刻观测脑形态学改变、谷氨酸(Glu)含量、凋亡细胞计数、Bcl-2蛋白表达. 结果(1)HIBD 48 h组Glu(1162.2±108.1)mg/kg,较假手术组(750.9±53.4)mg/kg明显升高(P＜0.05);HIBD组凋亡细胞计数[24 h:(7.6±1.9)%,48 h(12.6±1.2)%,72 h:(1 3.8±0.9)%],较假手术组[24 h(2.0±0.2)%,48 h(2.0±0.3)%,72 h(2.0±0.2)%]明显增加(P均＜0.05).(2)与对照组相比,RH-IGF-1组脑组织病变减轻;干预48 h组Glu[SRH-IGF-1组(781.4±54.2)mg/kg,RH-IGF-1组(740.5±46.6)mg/kg],较对照组(1126.6±48.0)mg/kg明显降低(P均＜0.05);RH-IGF-1组凋亡细胞计数[24 h:(3.6±0.9)%,48 h(8.2±2.2)%,72 h(9.4±1.4)%],较对照组[24 h(7.6±1.9)%,48 h(12.6±1.6)%,72 h(13.9±0.4)%]明显降低(P均＜0.05),RH IGF-1 48 h、72 h组Bcl-2蛋白表达阳性率分别为71.4%,71.4%,较对照组14.2%,14.2%明显升高(P均＜0.05). 结论(1)IGF 1可明显降低损伤脑中Glu含量,阻断Glu的脑损伤途径.(2)IGF-1通过降低细胞凋亡、提高保护性Bcl-2蛋白表达以避免和改善HIBD,并呈剂量依赖效应。