代谢型谷氨酸受体拮抗剂MCPG对大鼠弥漫性脑损伤的保护作用

MCPG protects brain tissues after diffuse brain injury in rats

目的 观察和探讨代谢型谷氨酸受体拮抗剂 α-甲基 ,4-羧基苯丙氨酸 (MCPG)对大鼠弥漫性脑损伤 (DBI)的保护作用及其机制 .方法 在自由落体致 DBI模型的基础上 ,通过测定脑组织含水量、TXB2 ,6 - keto- PGF1α,c AMP,c GMP等水平变化 ,以及应用硝酸镧标记电镜分析观察血脑屏障的通透性改变 ,探讨 MCPG对 DBI的保护作用及其机制 .结果 DBI后脑组织含水量增加 ,TXB2 ,c GMP,TXB2 /6 - keto-PGF1α升高 ,c AMP,6 - keto- PGF1α,c AMP/c GMP降低 ,硝酸镧标记电镜可见硝酸镧颗粒透过毛细血管壁渗透并沉积于脑组织内 ,血脑屏障开放 .应用 MCPG后 ,脑组织含水量下降(P<0 .0 1) ,伤后 2 4h后 TXB2 和 6 - keto- PGF1α升高幅度均有下降 (P<0 .0 5 ) ,c AMP/c GMP比值回升 (P<0 .0 1) .硝酸镧标记电镜显示通过毛细血管渗透到脑组织中的硝酸镧沉淀颗粒减少 ,血脑屏障的通透性下降 .结论 MCPG对大鼠 DBI具有保护作用 ,它是通过与 m Glu R1 和 m Glu R2 结合 ,竞争抑制 Glu通过二者所介导的信号传导机制 。

AIM To observe and to study the mechanism and protective effect of α methyl 4 carboxyphenyl glycine (MCPG), a metabotropic glutamate receptor antagonist, on the brain tissues after diffuse brain injury (DBI) in rats. METHODS On the basis of the animal model of traumatic DBI caused by free dropping, we measured the water content, the levels of TXB 2, 6 keto PGF 1α , cAMP and cGMP, and observed the changes of the blood brain barrier (BBB) permissibility by the Lanthanum Nitrate labeled electroscope to assess the protective effect of MCPG on the brain tissues after DBI in rats. RESULTS After DBI, the water content, the levels of TXB 2 and cGMP and the ratio of TXB 2/6 keto PGF 1α in rats brain rose while the levels of 6 keto PGF 1α and cAMP and the ratio of cAMP/cGMP decreased. Under the Lanthanum Nitrate labeled electroscope we was able to see the Lanthanum Nitrate granules infiltrate and deposit into the brain interstitial through the capillary which demonstrated the blood brain barrier was open. In the MCPG administration groups, the water content in the brain tissues declined distinctly ( P <0.01), the amplitudes of the TXB 2 and 6 keto PGF 1α rose 24 hours after injury decreased ( P <0.05), while the ratio of cAMP/cGMP recovered distinctly ( P < 0.01 ). Under the Lanthanum Nitrate labeled electroscope we saw the Lanthanum Nitrate granules infiltrate into the brain interstitial less than those in the DBI groups which manifest the blood brain barrier permissibility decreased. CONCLUSION MCPG administration is useful in protecting the brain tissues against DBI through affecting the combination of glutamate (Glu) with the mGluR subtype 1 and 2 to inhibit the signal transduction and modulate the biochemical metabolism of the neurons and the glial cells.