Chen Huijin, Liu Zhiwei, Zhou Zehan, Jiang Minhua, Qian Longhua, Wu Shengmei
Xinhua Hospital, Shanghai Second Medical University, Shanghai 200092, China.
Chin Med J (Engl). 2003 Apr;116(4):558-64.
To evaluate the neuroprotective effect of memantine, a non-competitive antagonist at the N-methyl-D-aspartate receptor, against hypoxic ischemia (HI) by exploring its regulation on the expression and synthesis of heat shock protein 70 (HSP70) gene in neonatal rat models with cerebral HI.
Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rat models either before (PRE group) or after (POST group) induction of HI. The expression and synthesis of the HSP70 gene and its corresponding product were determined by rapid competitive PCR and immunohistochemistry, respectively.
There was an increase in the expression of HSP70 mRNA two hours after induction of HI, which reached its peak at 48 hours, then decreased gradually. The same expression occurred at relatively low levels in the control group. Also, HSP70 synthesis was detected as early as 2h after HI, reached its peak between 48 and 72 hours, then declined over time. After memantine administration, the expression of the gene and its synthesis of the corresponding product decreased significantly during the time intervals 24 - 72 h for the gene and 48 - 72 h for the product compared to the HI group.
It was shown that HI is very sensitive to the expression of the HSP70 gene and synthesis of its corresponding product, which could be regulated by memantine. The latter may have the ability to reduce brain damage; thus decreased HSP70 mRNA expression could be a marker for HI. It is suggested that memantine can be a promising agent for neuroprotection against HI, although an overall and objective assessment of memantine is required to see if it can be used on neonates clinically later on.
通过探讨美金刚（一种N - 甲基 - D - 天冬氨酸受体非竞争性拮抗剂）对新生大鼠脑缺氧缺血（HI）模型中热休克蛋白70（HSP70）基因表达和合成的调节作用，评估其对HI的神经保护作用。
在新生大鼠HI模型中，于HI诱导前（预处理组）或诱导后（后处理组）以20mg/kg的剂量腹腔注射美金刚。分别通过快速竞争性PCR和免疫组织化学法测定HSP70基因的表达和合成及其相应产物。
HI诱导后2小时，HSP70 mRNA表达增加，在48小时达到峰值，然后逐渐下降。对照组中该表达处于相对较低水平。此外，HI后2小时最早检测到HSP70合成，在48至72小时达到峰值，然后随时间下降。与HI组相比，给予美金刚后，在24 - 72小时（基因方面）和48 - 72小时（产物方面）的时间间隔内，该基因的表达及其相应产物的合成显著降低。
结果表明，HI对HSP70基因的表达及其相应产物的合成非常敏感，且可由美金刚调节。后者可能具有减轻脑损伤的能力；因此HSP70 mRNA表达降低可能是HI的一个标志物。提示美金刚可能是一种有前景的抗HI神经保护剂，不过需要对美金刚进行全面客观的评估，以确定其日后是否可用于临床新生儿。
