| Stroke is one of the serious diseases in human, which leads to the irreversibility of brain function and structure, and its prognosis in clinic is poor. It is well known that the injury induced by ischemia and reperfusion plays an important role in stroke, therefore, researchers are studying the mechanisms of this disease and ways to prevent this injury to the brain. Experiments in mouse and rat model has shown that the L-tetrahydropalmatine(L-THP) has effected on brain ischemia. However, there was little report about the protection mechanism of L-THP on brain ischemia, especially in the histological and cell molecular level. In this paper, the neuroprotective effects and mechanisms of L-THP on the ischemia and reperfusion injury was studied. The result as follows:1 , L-THP protected from brain ischemia through decreasing the production and release of glutamateWe studied the effect of L-THP on the changes of level of amino acids (Asp, Glu, Tau, GABA) content in the mouse after global ischemia. Results showed that level of amino acids content including glutamate, GABA, Glu/GABA increased in the ischemia group. L-THP with the doses of 10,50,100μg/ml Can reduce the Glutamate content and Glu/GABA ratio but only low dose of L-THP can reduce the GABA content. We conclude that L-THP protect brain from ischemia through decreasing glutamate content in the brain.2. L-THP relieved the reversible and irreversible injury after hippocampal slices ischemiaThe protective effects of L-THP against hypoxic brain injury were studied by the extracellular recording technique in rat hippocampal slices. The results showed that treated with L-tetrahydropalmatine at the doses of 10,50,100 μg/ml, the time for the appearance of attenuation and disappearance time of PS were significantly postponed comparing with the ischemia group. The appearance of hypoxic injury potential (HIP) was delayed significantly and the appearance ratio of HIP was lower in L-tetrahydropalmatine group(with the doses of 10,50,100 μg/ml) and the recoveryamplitude of PS after reoxygenation was significantly higher than that of OGD group. Therefore, the above results showed that L-THP increased the ability against brain hypoxic injury and decrease the reversible and irreversible hypoxic injury in hippocampal slices.3. L-THP protect from injury through decreasing endothelium injury after ischemia from free adical and the production of ICAM-1 and E-selectin.We found with the primary HUVEC culture that cultured with LPS, the production of ICAM-1 and E-selectin increased significantly. Only L-THP at the dose of 100μg/ml can reduce the production of ICAM-1 and THP 50,100μg/ml could reduce the production of E-selectin. Metabolize activity of endothelium decrease when exposed with H2O2. Only L-THP at a dose of 50μg/ml could significantly reverse the effect of H2O2. All doses of L-THP significantly and dose dependently reverse the increasement of endothelium necrosis ratio induced by H2O2. So we conclude that L-THP decrease the appearance of endothelium injury after ischemia and keep the integrity of the blood-brain barrier. It may be the mechanism of the protective effect of L-THP.4. L-THP relieve the injury of cultured hippocampal cell through reducing the production of NO and O2In this study, the generation of NO and changes in intracellular Ca2+ were evaluated. Results showed that OGD induced an increase in NO production and intracellular Ca2+ concentration ([Ca2+]i)and the O2. L-THP at the dose of 100μg/ml could not significantly reduced the OGD-induced elevation of [Ca2+]i whereas the increase in NO and O2production was attenuated by L-THP at the dose of 100μg/ml. From above, we found that L-THP could not significantly reduced the OGD-induced elevation of [Ca2+]j and the reason might be that L-THP was an L-type calcium channel antagonist whereas the increasement of intracellular Ca2+ concentration might be through the NMDA-controlled calcium channel and N-type calcium channel. L-THP decreased the production of NO by reducing the production of NOSIIImRNA and decreased...
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