ABSTRACT
Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi ( SMP-SS-RQ) . Methods The depression model of chronic un-predictable mild stress ( CUMS ) was established in mice. The animals were randomly divided into control group, model group, SMP-SSRQ low, middle and high dose groups (8, 16, 32 mg·kg-1), with 12 mice for each group. The control group and the model group were given the same volume of saline, and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were deter-mined by open field experiment, sugar consumption test, forced swimming test and tail suspension test. Quantitative real-time PCR (qPCR) and Western blot were respectively performed to detect mRNA and pro-tein expression levels of Igsf11 , Pdia2 and Sec14 l2 inprefrontal cortex and hippocampus. Results Com-pared with model group, depressed mice' s horizontal mobile score, upright number and the sugar water pref-erence index increased and FST as well as TST de-creased in all SMP-SSRQ groups(P<0.05). The de-pression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression lev-el of Igsf11 , Pdia2 and Sec14 l2 in the prefrontal cortex and hippocampus of the depressed mice, presenting significant statistical difference compared with model group ( P<0.05 ) . Conclusions SMP-SSRQ can ef-fectively improve mouse depressive behavior, and its mechanism may be related to the down-regulation of Igsf11 , Pdia2 and Sec14 l2 in mouse prefrontal cortex and hippocampus.
ABSTRACT
Using whole-cell patch clamp technique this study investigated the effects of adenosine (Ado) on action potential, L-type calcium current (I(Ca.L)), delayed afterdepolarizations (DADs), and transient inward current (I(ti)) induced by isoproterenol (Iso) in guinea pig isolated single ventricular myocytes. The results showed: (1) Ado alone had no significant direct effects on action potential and I(Ca.L) in guinea pig ventricular myocytes at 20-100 micromol/L. However, Ado significantly attenuated the prolongation of action potential duration (APD) and the increase of the peak amplitude of I(Ca.L) induced by Iso. Iso (10 nmol/L) markedly increased APD(50) and APD(90) from 340+/-21 ms to 486+/-28 ms and from 361+/-17 ms to 501+/-29 ms, respectively (P<0.01), and increased the amplitude of I(Ca.L) from 6.53+/-1.4 pA/pF to 18.28+/-2.4 pA/pF (P<0.01). The peak potential of current-potential relationship shifted to the left. Ado (50 micromol/L) abbreviated APD(50), APD(90) to 403+/-19 ms and 419+/-26 ms (P<0.01), and decreased the peak amplitude of I(Ca.L) to 10.2+/-1.5 pA/pF (P<0.01 vs Iso), but did not change resting membrane potential (RMP), action potential amplitude (APA), and overshoot (OS). (2) Iso (30 nmol/L) reproducibly elicited DADs with 100% incidence of DADs under this condition. Ado (50 micromol/L) completely inhibited Iso from inducing DADs. Iso (30 nmol/L) elicited I(ti) with 2-second depolarizing voltage-clamp pulses rising to +20 mV from a holding potential of -40 mV, the incidence of I(ti) being 100%, and the I(ti) was suppressed in the presence of Ado (50 micromol/L) with the incidence of I(ti) decreased to 14.3% (P<0.05). These data indicate that Ado antagonizes the stimulatory effect of Iso, and that the antiarrhythmic mechanism of Ado preventing Iso-induced DADs is due to the inhibition of intracellular Ca(2+) overload through attenuating the prolongation of APD, the enhance of I(Ca.L) and I(ti).