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【目的】研究代表不同胎龄新生儿缺氧缺血性脑病(hypoxic ischemic encephalopathy,HIE)的模型鼠脑组织中谷氨酸(glutamate,Glu)含量变化的时间依从性及干预措施。【方法】将128只新生SD大鼠按出生日龄(postna-tal age,P)分为P2、P6、P12、P18 4组,每组32只;各组按不同干预措施分为缺氧缺血性脑损伤(hypoxic ischemic braindamage,HIBD)模型对照组(H)、α-氨基羟甲基恶唑丙酸(AMPA)干预组(A)、GYKI52466干预组(G)与空白对照组(N),每组8只。除N组外,各组参照Rice方法建立HIBD标准模型,A、G组于造摸后立即给药。用药6h后采集标本,检测各组脑组织Glu含量,同时做病理学检查。【结果】各日龄组脑组织中Glu含量比较,Glu含量与日龄呈负相关(r=0.81,P<0.01),P2组含量最高,与P6、P12、P18组比较差异均有统计学意义[(670.2±139.4)μmol/gprot vs(576±139)μmol/gprot,(670.2±139.4)μmol/gprot vs(441.9±114.9)μmol/gprot,(670.2±139.4)μmol/gprot vs(287.0±82.8)μmol/gprot,Q=3.88,9.41,15.80,P<0.05或<0.01]。各日龄组内比较,G组脑组织中Glu含量明显低于A组、H组和N组[(348.6±128.5)μmol/gprot vs(608.6±176.7)μmol/gprot,(348.6±128.5)μmol/gprot vs(554.2±206.2)μmol/gprot,(348.6±128.5)μmol/gprot vs(463.8±167.1)μmol/gprot,Q=10.72,8.49,4.75,P均<0.01]。病理学改变与Glu含量变化呈一致性。【结论】不同日龄新生大鼠脑组织中,Glu的含量具有时间依从性,与日龄呈负相关;HIBD可导致Glu含量明显增加而加重脑损伤;而GYKI52466可显著降低Glu含量,从而发挥神经保护作用,且胎龄越小,效果越明显。故应用GYKI52466早期干预可望有效防治因早产、窒息导致新生儿脑损伤。
【OBJECTIVE】 To study the time compliance and intervention of the changes of glutamate (Glu) content in brain tissue of neonatal hypoxic ischemic encephalopathy (HIE). 【Methods】 128 newborn SD rats were divided into P2, P6, P12 and P184 groups according to their postnatal age (P), 32 in each group. Each group was divided into three groups according to different interventions: hypoxia The HIBD model group (A), the GYKI52466 intervention group (G) and the blank control group (N), the control group (H), the AMPA group (A), the Hypoxic ischemic braindamage , Each group of 8. In addition to the N group, each group with reference to Rice method to establish HIBD standard model, A, G group immediately after making touch. After 6 hours, the specimens were collected and the content of Glu in brain tissue of each group was detected. At the same time, pathological examination was performed. 【Results】 Compared with the P6, P12 and P18 groups, there was a significant difference in the content of Glu in brain tissues between different age groups. The content of Glu was negatively correlated with age (r = 0.81, P <0.01) (670.2 ± 139.4) μmol / gprot vs (576 ± 139) μmol / gprot, (670.2 ± 139.4) μmol / gprot vs (441.9 ± 114.9) μmol / gprot vs 82.8) μmol / g prot, Q = 3.88, 9.41, 15.80, P <0.05 or <0.01]. The content of Glu in group G was significantly lower than that in group A, group H and group N [(348.6 ± 128.5) μmol / gprot vs (608.6 ± 176.7) μmol / gprot, (348.6 ± 128.5) μmol / gprot vs (554.2 ± 206.2) μmol / gprot, (348.6 ± 128.5) μmol / gprot vs (463.8 ± 167.1) μmol / gprot, Q = 10.72, 8.49 and 4.75, P all <0.01]. Pathological changes and changes in Glu content were consistent. 【Conclusion】 The contents of Glu in brain tissues of neonatal rats of different ages are time-dependent and negatively correlated with the age. HIBD can lead to a significant increase of Glu content and aggravate brain injury. GYKI52466 can significantly reduce Glu content, Neuroprotective effects, and gestational age smaller, the effect is more obvious. Therefore, the application of GYKI52466 early intervention is expected to be effective prevention and treatment of premature birth, asphyxia neonatal brain injury.