| ObjectiveTo discuss the action mechanism of Naotongliting capsule as a new medicine used to treat patients with migraine both on long term protective function and immediate effect of alleviating pain.MethodsBoth ancient and modern traditional Chinese medicine (TCM) prescriptions used to cure migraine are collected for finding the general rule of herb selection among those prescriptions by statistical analyzing;After making rat model with migraine by electrostimulating superior sagittal sinus(SSS),the model rats are treated whit Naotongliting capsule meanwhile taking Naproxen Sodium as positive control .The protein products of c-fos and c-jun gene in brine stem and hypothalamus of rats are tested with immunohistochemical method SABC.The content of calaitonin gene related peptide(CGRP) and endothelin(ET) in blood plasma of rats is measured by means of radioimmunity test; Mice model with migraine caused by exhausting 5-hydroxytryptamine(5-HT) with Reserpine is built up ,then the model mice are treated whit Naotongliting capsule.Fufangyangjiao capsule is used as control medicine.The content of 5-HT, 5-hydroxyindole acetic acid(5-HIAA),dopamine(DA),homovanillic acid(HVA),dihydroxyphenylacetic acid(DOPAC)and norepinephrine(NE)in brain and blood plasma of mice are tested by electrochemical meathod.The level of leucine enkephalin(L-EK) andβ- endorphin(β-EP) in brain of mice is tested with radioimmunity method;Staircase test and anti-anxiety test are used to estimate the dissipate anxiety effect of Naotongliting capsuleResults1. The herbal medicine which have functions of dispelling wind-evil, dispersing cold and alleviating pain are most widely used not only in ancient TCM prescriptions, but also modern TCM prescriptions. Among the TCM prescriptions treating migraine.Chuanxiong, Baizhi and Xixin are used most frequently, and most of those prescriptions have efficacy virtue of stimulating circulation to end stasis, expelling the obstruction from collaterals and calming the liver to stop the wind.2. Model rats with migraine caused by electrostimulating SSS have more cells which express protein products of c-fos and c-jun gene in brine stem and hypothalamus ,and the area of c-fos and c-jun positive cells is higher than normal control group and false operation group. Naotongliting capsule can decrease the mumber and the area of c-fos and c-jun positive cells of model rats.Big dose therapy group has better effect that is similar to Naproxen Sodium.3. The level of CGRP and ET in blood plasma of model rats with migraine caused by electrostimulating SSS is upregulated. Naotongliting capsule can downregulate the level of CGRP in blood plasma of model rats,but it has no obvious effect on upregulated ET level .4. According to the results of this research, ICR mouse is sensitive to Reserpine.The dose of Reserpine ICR mouse can endureis quite different to this of KM mouse that is reported in articles. In this experiment ,the dose of Reserpine giving to ICR mouse is 0.25mg/kg when causing mice model with migraine successfuly.The content of 5-HT,DA and NE in blood plasma and brain stem and hypothalamus is decreased obviously.5. Model mice with migraine caused by exhausting 5-HT with Reserpine have low temperature and low body weight and short blood clotting time.The content of 5-HT,DA in blood plasma ,brain stem and hypothalamus of model Mice is decreased ,and NE,HVA in brine stem and hypothalamus is decreased too. Naotongliting capsule can better the general condition of model mice, increase temperature and body weight, prolong blood clotting time of model mice;Meanwhile the content of 5-HT,DA in blood plasma ,brain stem and hypothalamus of model mice are increased,and the content of DOPAC in plasma is downregulated. The effect is similar to Fufangyangjiao capsule.But Naotongliting capsule has no obvious effect on 5-HIAA and DA in plasma.6. Model mice with migraine caused by exhausting 5-HT with Reserpine not only have lower content of 5-HT and DA in plasma, brain stem and hypothalamus, lower content of NE in brine stem and hypothalamus,but also have lower level of L-EK andβ-EP in brain than normal control and false injection groups. Naotongliting capsule can also upregulate the level of L-EK andβ-EP in brine, when upregulate the content of 5-HT and DA in plasma and brain stem and hypothalamus, upregulate the content of NE in brain of model mice.There is an obvious relation between effect and dose.7. The Naotongliting capsule can increases frequency with which the mice stride over the light-dark chambers,and abbreviate the time of mice staying in the dark chamber;Meanwhile It can increases the number of staircases that the mice clamber,and decreases the frequency with which the mice arises.Conclusions1. Naotongliting capsule could give its immediate effect of alleviating pain by following mechanism:restraining the expression of c-fos and c-jun gene by some kind of way, weakening or stopping the conduction of pain stimulation in the center nerves system;Downregulating the level of CGRP in plasma to regulate the function of blood vessel and improv anti-inflammatory effect;Upregulating the level of 5-HT and DA in plasma , brain stem and hypothalamus, increasing the content of NE in brine stem and hypothalamus,to regulate function disorder of blood vessel in brain;Regulating function of thrombocyte, abating the blood clotting condition to improving the blood circulation in brain.2. Naotongliting capsule could give its long term protective function by following mechanism: Upregulating the level of 5-HT, NE, DA, L-EK andβ-EP in brain,to improve the function of pain modulation of the center nerves system; Calming the anxiety symptoms of patients with migraine. |
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