Effect Of Lidocaine On The Level Of Glutamate And Cell Apoptosis In Rat Brain After Ischemic Injury

Background and Objective: Brain anoxemia caused by such factors as acute cerebrovascular injury, cardiac muscle injury, cardiac arrest, toxicosis and so on is the common pathogeny of the central neural system injury. The mechanism of ischemic injury held nowadays is: (1) cytotoxicity of toluene caused by excited amino acid; (2) injury caused in nerve cell after ischemic, cell calsium ovevload, mitochondrial permeability transtion(MPT); (4) The expression of some new apoptosis gene induces the process of apoptosis; (5) the response of inflammation. In recent years, the protective mechanism of lidocaine on ischemic injury has been drawing researcher's more and more attention, related study on protective effect and mechanism have been put up more. Lidocaine is a kind of local anesthetic used commonly in clinic, except the effect of anaesthesia, it is also used to treat ventricular arrhythmia. The aim of this study is to investigate the effect of lidocaine on the level of glutamate and cellular apoptosis in rat brain after ischemic injury so as to accumulate experimental data for the selection of medicine in clinical complex.. Method: 40 male SD rats, 8~12 weeks old, weight 170~210 gram, were prepared. To be ligated the bilateral common carotid arteries at first, and inject embolus into it, and then take off the clamp to let the bilateral common carotid arteries be normal. The animal model of brain with poly-embolism was gotten. 40 male SD rats were divided into 4 groups at random, 10 rats each group. Group I was taken as the control , group II is the sham-operation control group, group III are on operation and group IV are treated with lidocanine . Rats were executed by breaking neck to the point of 24hs after operation. Take the rat brain out of the skull on icy plate at once. Then isolate left hippocampus to be homogenized and take the supernatant, to detect thelevel of glutamate by high performance liquid chromatography (HPLC) .The right hippocampus were isolated. Fixed with poly-formaldehyde, cut into slide. Routine HE staining to check the structure of tissue .The level of Bax was explored by immunochemistry method. TUNEL was employed to measure the cell apoptosis. Result: 1.The changes of glutamate content in rat brain:(l) The level of glutamate in the sham-operation control group got a little increase, but there is no significant difference as compared with the control group (p>0.05). (2) The glutamate level in model group significantly decreased as compared with that of the control group(p<0.05). (3)There is a little decrease in the level of glutamate in group treatd with lodocaine,but there is no significant difference as compared with model group (p>0.05); 2. The slide with HE staining show that the structure of nerve cells in the control group is in nature. Less swelling and less necrosis of nerve cells can be found in the sham-operation control group。 Nerve cells in operated group can be found with heavily swelling and big opague of necrosis. The injury and necrosis in group treated with drug was less than those of operated group. 3. The results of TUNNEL : (l)There was much less apoptosis in control group, and there was less apoptosis in sham-operation group. There is no significant difference between these two groups(p>0.05); (2) The rate of cell apoptosis in operated group increased notablely. There was significance as compared with control group(p<0.05);(3) The rate of cell apoptosis in lidocaine-treated group decreased notablely. There was significance compared with control group 4. Immunochemical result of Bax: The expression of Bax can be detected in every group. (1) the number of Bax-positive cells in the sham-operation control group is more than that of the control group , but there was no significant difference(p>0.05). (2) the number of positive cells in lidocaine-treated group difference (p<0.05) is less than that of the operated group remarkably, and there is significant difference between these two groups (p<0.05) . Conclusion: 1. In rat ischemic brain, lidocaine can decrease the level of glutamic acid to some extent, but has no effect of depressing glutamate statistically; 2. Lidocaine may reduce the expression of Bax in nerve cells; 3. Lidocaine can possibly depress the apoptosis of never cells .