| In nowadays, there are few researches of Traditional Chinese Medicine (TCM) that are targeted by ion channels. However, it is very necessarily important to evaluate the drug toxicity and exploit new drugs based on targeting ion channels. This thesis contains three parts. We tried to deal with some researches on several kinds of common Traditional Chinese Medicine (TCM) by targeting different ion channels (including:Cav1.2, Cav2.1, Cav2.3, Cav3.1, BK channel, KCNQ1, KCNQ1/KCNE1, KCNQ1/KCNE3 and KCNH2). Firstly, because Panax Notoginseng has been used clinically to cure the hypertension, the effects of RPNS were further evaluated on different ion channels related to cardiovascular and nervous systems. Secondly, based on the pain and insomnia therapy of Valeriana jatamansi Jones, the effects of some compounds from Valeriana jatamansi Jones were tested on ion channels related to the pains and insomnia. And those findings can provide the theoretic and practical support in the clinical use of Valeriana jatamansi Jones. Finally, by knowing the physiological functions of different ion channels and the pharmacological effects of different TCM, the compounds screening experiment were carried out on different ion channels.Charpter One:Vasodilatory effect of Root Saponins of Panax Notoginseng on mice thoracic aorta vasoconstriction induced by depolarization and its activities on ion channelsThe ex-vivo vasodilatory effects of RPNS (0.6,1, and4 g-L-1), Xuesaitong(0.6,1, and 4g·L-1) and Nifedipineare (10μmol·L-1) were measured on isolated endothelium-denuded thoracic aortas induced by 60 mmol·L-1KCl. The effects of RPNS (1g·L-1) were evaluated by use of two-electrode voltage clamp method on different channels (Including Cav1.2, Cav2.1, Cav2.2, Cav3.1, KCNH2, KCNQ1, KCNQ1/KCNE1 and BK channel) that were expressed in Xenopus laevis oocytes. Compared with blank control, the ex-vivo aortas experiment showed that RPNS (0.6,1, 4g·L-1) and Nifedipine (10μmol·L-1) had thorough vasodilatory effects on the endothelium-denuded aortas pre-constricted by 60 mmol·L -1KCl (P<0.01), but Xuesaitong (0.6,1,4g·L-1) had weak vasodilatory activity in the same condition and their vasodilatory ratios were (1.5±0.5)%, (7.3±1.2)% and (17.7±1.7)%(P<0.05 P<0.01), respectively. Compared with blank control, the method of tow-electrode voltage clamp showed that RPNS (1 g·L-1) had obviously inhibitory effects on Cav1.2, Cav2.2 and Cav3.1, and the inhibitory ratios of RPNS (1g·L-1) on the peak current of Cav1.2, Cav2.2 and Cav3.1 were (57.1±8.6)%, (17.2±0.7)%　and (50±6.8)%(P<0.01), respectively. RPNS (1g·L-1) had obviously activated effect on BK channel, and the activated ratio of RPNS (1g·L-1) on the peak current of BK channel was (37.9±2.7)% (P<0,01). However, RPNS (1g·L-1) show no significant effect on the other channels (Cav2.1, KCNH2, KCNQ1 and KCNQ1/KCNE1). The endothelium-independent vasodilatation of RPNS is related to the inhibition of Cav1.2 and Cav3.1 as well as activation of BK channel. But the endothelium-independent vasodilatation of Xuesaitong was very tiny. RPNS rather than Xuesaitong has some unknown molecules that can cause endothelium-independent vasodilatation. RPNS little effects on the other ion channels (Including Cav2.1, Cav2.2, KCNH2, KCNQ1 and KCNQ1/KCNE1), indicating that RPNS have little effects on heart and nervous system.Charpter Tow:Effects of different compounds from V. jatamansi Jones on different ion channelsThe effects of different compounds from V. jatamansi Jones were evaluated by use of two-electrode voltage clamp method on different channels (Including Cav1.2, Cav2.1, Cav2.2, Cav2.3, Cav3.1, BK channel, KCNQ1 and KCNH2) that were expressed in Xenopus laevis oocytes. Compared with blank control, the method of tow-electrode voltage clamp showed that 12 compounds (30μ.mol·L-1:zjv27, zjv31, zsj3, zsj4, zsj14, zsj16, zsj11a, zsj17a, zsj　10, zsj 12, zsj 15 and zsj 17c) had obviously inhibitory effects on Cav2.2 and Cav3.1, and the average inhibitory ratios of them on the peak current of Cav2.2 and Cav3.1 were 50%(P<0.05), and the EC50 of 8 compounds (including:zjv27, zjv31, zsj3, zsj4, zsj14, zsj16, zsj11a and zsj17a) is differentiated from 0.1μmol·L-1 from 8μmol-L-1, however, all those compounds could not totally inhibit Cav2.2 and Cav3.1, suggesting that those compounds would not cause any abnormal effects on organism as results of its blockade of Cav2.2 and Cav3.1. The inhibitory effects on Cav2.2 and Cav3.1 is closely consistent with the pharmachology of V. jatamansi Jones to cure the abdomine pain and increase sleep.Charpter Three:Effects of different compounds from other Chinese traditional trugs on different ion channelsThe effects of different compounds from several Chinese traditional trugs were evaluated by use of two-electrode voltage clamp method on different channels (Including Cav1.2, Cav2.1, Cav2.2, Cav3.1, BK channel, KCNQ1/KCNE1, KCNQ1/KCNE3, KCNQ1 and KCNH2) that were expressed in Xenopus laevis oocytes.Compared with blank control, the method of tow-electrode voltage clamp showed that no compound (30 umol·L-1) had any obvious inhibitory effects on those ion channels. |
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