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ABSTRACT: To explore the relationship between the effect of electroacupuncture (EA) and EA of different layer tissues of the acupoint area and different acupoints in upregulating mean arterial pressure (MAP) and heart rate (HR) in hypotension plus bradycardia rats.
A total of 200 SD rats were used in the present study. Bradycardia plus hypotension model was established by intravenous injection of 0.4% propranolol (0.4 mg/100 g, maintaining dosage 0.025 mg/100 g per minute). EA (2 Hz/15 Hz, 5 mA) was applied to (1) right "Daling" (PC7) and "Jiexi" (ST 41), "Ximen" (PC 4) and "Housanli" (ST 36), "Quze" (PC 3) and "Dubi" (ST 35) which have a similar tissue structure, and are located in the upper and lower limbs and different meridians, and non-acupoint [3 mm left-superior to the "Tianshu" (ST 25)], (2) skin, muscle layer and periosteum part of "Ximen" (PC4), (3) skin, muscle layer and periosteum of "Housanli" (ST36) for 15 min. The HR and MAP were recorded by using a multi-channel physiological signal sampling-processing system.
(1) In comparison with the model group, the percentages of the increased HR and MAP in the "Ximen" (PC4), "Quze" (PC3), "Housanli" (ST 36) and "Jiexi" (ST41) groups, PC 4-skin, PC 4-muscle, PC 4-periosteum, ST 36-skin, ST 36-muscle and ST 36 periosteum groups, and the increased HR in the "Dubi" (ST 35) group were upregulated significantly (P < 0.05, P < 0.01). The percentages of the increased HR and MAP were significantly higher in the "Quze" (PC3) and "Ximen" (PC4) groups than in the "Daling" (PC7) group (P < 0.01), and the increased HR evidently higher in the "Housanli" (ST36) and "Jiexi" (ST41) groups than in the "Dubi" (ST35) group (P < 0.01), suggesting different effects of EA stimulation of different acupoints in the same one meridian. No significant differences were found among the "Ximen" (PC4), "Quze" (PC3), "Housanli" (ST36) and "Jiexi" (ST 41) groups, and between the "Daling" (PC7) and model groups, and between the non-acupoint and model groups in the rising rates of both HR and MAP (P > 0.05). (2) Regarding the effects of EA of different tissue layers in "Ximen" (PC4) and "Housanli" (ST36) areas, the rising rates of HR were markedly higher in the PC 4-skin group than in the "Ximen" (PC4), PC4-muscle and PC 4-periosteum groups (P < 0.01), and considerably higher in the "Housanli" (ST36), ST 36-skin, and ST 36-muscle groups than in ST 36-periosteum group (P < 0.05). The rising rates of MAP were significantly higher in the PC 4-skin and PC 4-muscle groups than in the "Ximen" (PC4) and PC4-periosteum groups (P < 0.01), and considerably higher in the ST36-skin group than in the "Housanli" (ST36), ST36-muscle and ST36-periosteum groups (P < 0.01), suggesting different effects of EA stimulation of different tissue layers in the same one acupoint. No significant differences were found between the "Ximen" (PC 4) and PC 4-muscle groups, among the "Housanli" (ST36), ST36-skin and ST 36-muscle groups in the rising rates of HR, between the "Ximen" (PC 4) and PC4-periosteum groups, and among the "Housanli" (ST36), ST 36-muscle and ST36-periosteum groups in the rising rates of MAP (P > 0.05). (3) The effect of the PC 4-skin group was significantly superior to that of the ST 36-skin group in increasing HR (P < 0.01), and the effect of the PC 4-muscle group was obviously stronger than that of the ST 36-muscle group in raising MAP (P < 0.01), suggesting different therapeutic effects of EA stimulation of the similar tissue in different meridian-acupoints. The effects of the "Ximen"(PC4) and "Housanli" (ST36) groups in raising both HR and MAP, and that of the PC 4-muscle and ST 36-muscle groups in upregulating HR, and that of the PC 4-periosteum and ST 36-periosteum groups in raising MAP were comparable (P > 0.05).
EA of different acupoints of the same one meridian, the similar structure of different meridian acupoints and different tissue layers of the same one acupoint have their own relatively specific effects in upregulating HR and MAP in hypotension plus bradycardia rats.
Zhen ci yan jiu = Acupuncture research / [Zhongguo yi xue ke xue yuan Yi xue qing bao yan jiu suo bian ji] 12/2010; 35(6):422-8.
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ABSTRACT: Neferine was isolated from green seed embryo of Nelumbo nucifera Gaertn which has been used as an anti-obesity agent in traditional Chinese herbal medicine.
This study was conducted to investigate the effects of neferine on enhancing insulin sensitivity in insulin resistant rats compared with rosiglitazone and to potentially reveal its role in mediating the anti-obesity properties of Nelumbo nucifera Gaertn.
Fasting blood glucose (FBG), fasting blood insulin (FINS), triglycerides (TG) and tumor necrosis factor-alpha (TNF-alpha) were measured, and the oral glucose tolerance test for 2-h plasma glucose level (2-h PG) was carried out. The glucose infusion rate (GIR) was used to measure the insulin sensitivity by hyperinsulinemic euglycemic clamp technique.
The levels of FBG, FINS, TG, TNF-alpha and 2-h PG all decreased significantly in the rosiglitazone and neferine groups compared with the insulin resistance (IR) model group. Neferine diminished the 2-h PG more than did rosiglitazone treatment. Compared to the IR model group, the treatments of neferine and rosiglitazone remarkably increased GIRs but no difference between these two treatments themselves was evident.
These data demonstrate that neferine has effects similar to rosiglitazone in decreasing fasting blood glucose, insulin, TG, TNF-alpha and enhancing insulin sensitivity in insulin resistant rats.
Journal of ethnopharmacology 08/2009; 124(1):98-102. · 2.32 Impact Factor
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Long Chen,
Linlin Wang,
Bin Xu,
Guangxia Ni,
Li Yu,
Bin Han,
Xiaochun Yu,
Kelin Wang,
Yueyang Lai,
Shuyuan Zhou,
Quan Zhu
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ABSTRACT: Diabetes mellitus is associated with changes of alpha(1)-adrenoceptor (alpha(1)-AR) on heart electrical function and expression. In this study, we investigated the ionic basis underlying abnormal alpha(1)-AR mediated QT prolongation in the diabetic rat hearts.
Electrophysiological and biochemical techniques were used in Streptozotocin (STZ)-induced diabetic and control rat hearts.
In both control and diabetic rats, the alpha(1)-AR agonist, phenylephrine (PE, 10-100 microM) prolonged the rate-corrected QT intervals (QTc) and action potential durations at 30% (APD(30)) and 90% (APD(90)) repolarization levels with the increased QTc and APD(90) significantly greater in diabetic rats. PE significantly decreased the transient outward K(+) current (I(to)) and the steady-state K(+) current (I(ss)) in both control and diabetic rats but had no effects on the delayed rectifier K(+) current (I(k)). However, PE induced a greater reduction mainly in the I(ss), but not I(to), in diabetic rats. Furthermore, using RT-PCR and Western blot analyses, we found that alpha(1A)-ARs were over-expressed in the left ventricular tissues of the diabetic rat hearts at both the mRNA and the protein levels.
These data suggested that in diabetic hearts, a greater sensitivity of the alpha(1A)-AR mediated the larger suppression of I(ss) and resulted in a more prolonged APD(90) and QTc. Thus, higher alpha(1A)-AR expression levels in diabetic heart may underlie this type of diabetic cardiomyopathy and suggests that alpha(1A)-AR may serve as a therapeutic target.
Life Sciences 01/2009; 84(7-8):250-6. · 2.53 Impact Factor
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ABSTRACT: Prefrontal cortex (PFC) dopamine D1/5 receptors modulate long- and short-term neuronal plasticity that may contribute to cognitive functions. Synergistic to synaptic strength modulation, direct postsynaptic D1/5 receptor activation also modulates voltage-dependent ionic currents that regulate spike firing, thus altering the neuronal input-output relationships in a process called long-term potentiation of intrinsic excitability (LTP-IE). Here, the intracellular signals that mediate this D1/5 receptor-dependent LTP-IE were determined using whole cell current-clamp recordings in layer V/VI rat pyramidal neurons from PFC slices. After blockade of all major amino acid receptors (V(hold) = -65 mV) brief tetanic stimulation (20 Hz) of local afferents or application of the D1 agonist SKF81297 (0.2-50 microM) induced LTP-IE, as shown by a prolonged (>40 min) increase in depolarizing pulse-evoked spike firing. Pretreatment with the D1/5 antagonist SCH23390 (1 microM) blocked both the tetani- and D1/5 agonist-induced LTP-IE, suggesting a D1/5 receptor-mediated mechanism. The SKF81297-induced LTP-IE was significantly attenuated by Cd(2+), [Ca(2+)](i) chelation, by inhibition of phospholipase C, protein kinase-C, and Ca(2+)/calmodulin kinase-II, but not by inhibition of adenylate cyclase, protein kinase-A, MAP kinase, or L-type Ca(2+) channels. Thus this form of D1/5 receptor-mediated LTP-IE relied on Ca(2+) influx via non-L-type Ca(2+) channels, activation of PLC, intracellular Ca(2+) elevation, activation of Ca(2+)-dependent CaMKII, and PKC to mediate modulation of voltage-dependent ion channel(s). This D1/5 receptor-mediated modulation by PKC coexists with the previously described PKA-dependent modulation of K(+) and Ca(2+) currents to dynamically regulate overall excitability of PFC neurons.
Journal of Neurophysiology 04/2007; 97(3):2448-64. · 3.32 Impact Factor
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ABSTRACT: The prefrontal cortex plays a principal role in higher cognition and particularly in the fast online manipulation of appropriate information to guide forthcoming behavior. Dysfunction of this process represents a main feature in the pathophysiology of schizophrenia. Both dopamine D1 and N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex play a critical role in synaptic plasticity, memory mechanisms, and cognition. Recent data have shown that D1 and NMDA receptors interact bidirectionally and may greatly influence the output of the prefrontal cortex. Hypofunction of these receptor systems in the prefrontal cortex is found in schizophrenia. This review attempts to summarize some of the latest findings on the cellular mechanisms that underlie D1-NMDA receptor interactions. These findings have provided potential therapeutic strategies that aim to functionally up-regulate D1 and/or NMDA receptor safely via selective activation of D1 receptors or coagonist activation of NMDA receptors through blockade of the glycine transporter-1.
The Neuroscientist 11/2005; 11(5):452-70. · 4.57 Impact Factor
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ABSTRACT: The N-methyl-D-aspartate (NMDA) receptor (NMDA-R) has pivotal roles in neural development, learning, memory, and synaptic plasticity. Functional impairment of NMDA-R has been implicated in schizophrenia. NMDA-R activation requires glycine to act on the glycine-B (GlyB) site of the NMDA-R as an obligatory co-agonist with glutamate. Extracellular glycine near NMDA-R is regulated effectively by a glial glycine transporter (GlyT1). Using whole-cell voltage-clamp recordings in prefrontal cortex (PFC) slices, we have shown that exogenous GlyB site agonists glycine and D-serine, or a specific GlyT1 inhibitor N[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS) in the presence of exogenous glycine (10 microM), potentiated synaptically evoked NMDA excitatory postsynaptic currents (EPSCs) in vitro. Furthermore, in urethan-anesthetized rats, microiontophoretic NMDA pulses excite single PFC neurons. When these responses were blocked by approximately 50% to approximately 90% on continuous iontophoretic application of the GlyB site, antagonist (+)HA-966, intravenous NFPS (5 mg/kg), or a GlyB site agonist D-serine (50 mg/kg iv) reversed this (+)HA-966 block. NFPS may elevate endogenous glycine levels sufficiently to displace (+)HA-966 from the GlyB sites of the NMDA-R, thus enabling reactivation of the NMDA-Rs by iontophoretic NMDA applications. D-Serine (50-100 mg/kg iv) or NFPS (1-2 mg/kg iv) alone also augmented NMDA-evoked excitatory responses. These data suggest that direct GlyB site stimulation by D-serine, or blockade of GLYT1 to elevate endogenous glycine to act on unsaturated GlyB sites on NMDA-Rs, potentiated NMDA-R-mediated firing responses in rat PFC. Hence, blockade of GlyT1 to elevate glycine near the NMDA-R may activate hypofunctional NMDA-R, which has been implicated to play a critical role in the pathophysiology of schizophrenia.
Journal of Neurophysiology 03/2003; 89(2):691-703. · 3.32 Impact Factor
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ABSTRACT: The atypical antipsychotic drug clozapine effectively alleviates both negative and positive symptoms of schizophrenia via unclear cellular mechanisms. Clozapine may modulate both glutamatergic and dopaminergic transmission in the prefrontal cortex (PFC) to achieve part of its therapeutic actions. Using whole cell patch-clamp techniques, current-clamp recordings in layers V-VI pyramidal neurons from rat PFC slices showed that stimulation of local afferents (in 2 microM bicuculline) evoked mixed [AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors] glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs). Clozapine (1 microM) potentiated polysynaptically mediated evoked EPSPs (V(Hold) = -65 mV), or reversed EPSPs (rEPSP, V(Hold) = +20 mV) for >30 min. The potentiated EPSPs or rEPSPs were attenuated by elevating [Ca(2+)](O) (7 mM), by application of NMDA receptor antagonist 2-amino5-phosphonovaleric acid (50 microM), or by pretreatment with dopamine D1/D5 receptor antagonist SCH23390 (1 microM) but could be further enhanced by a dopamine reuptake inhibitor bupropion (1 microM). Clozapine had no significant effect on pharmacologically isolated evoked NMDA-rEPSP or AMPA-rEPSPs but increased spontaneous EPSPs without changing the steady-state resting membrane potential. Under voltage clamp, clozapine (1 microM) enhanced the frequency, and the number of low-amplitude (5-10 pA) AMPA receptor-mediated spontaneous EPSCs, while there was no such changes with the mini-EPSCs (in 1 microM TTX). Taken together these data suggest that acute clozapine can increase spike-dependent presynaptic release of glutamate and dopamine. The glutamate stimulates distal dendritic AMPA receptors to increase spontaneous EPSCs and enabled a voltage-dependent activation of neuronal NMDA receptors. The dopamine released stimulates postsynaptic D1 receptor to modulate a lasting potentiation of the NMDA receptor component of the glutamatergic synaptic responses in the PFC neuronal network. This sequence of early synaptic events induced by acute clozapine may comprise part of the activity that leads to later cognitive improvement in schizophrenia.
Journal of Neurophysiology 05/2002; 87(5):2324-36. · 3.32 Impact Factor
