OBJECTIVE: To explore the pathogenic mechanism of liver-yang hyperactivity type of hypertension and to observe the effects of Pinggan Qianyang Formula (PGQYF), a compound of traditional Chinese herbals for calming the liver and suppressing yang, so as to provide experimental evidence for new marker proteins of drug therapy. METHODS: A rat model of liver-yang hyperactivity was prepared with spontaneous hypertensive rats (SHRs) by administration of Aconiti Praeparatae Decoction. Adrenal proteins were separated by 2D gel electrophoresis (2-DE). The differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database analysis. RESULTS: The rat model of liver-yang hyperactivity was successfully reproduced, and the PGQYF could decrease the grades of irritability, conjunctival congestion and systolic blood pressure of the rats (P<0.05, P<0.01). After analysis, twelve obviously differentially expressed proteins were found, eight of which were identified. The expression levels of isocitrate dehydrogenase and steroidogenic acute regulatory protein in the untreated group were up-regulated as compared with those in the normal control group, and down-regulated in the treatment group. The expression levels of ferritin light chain, elongation factor Tu, Rho GDP disassociation inhibitor 1, flavin reductase and basic transcription factor 3 in the untreated group were down-regulated as compared with those in the normal control group, and up-regulated in the treatment group. CONCLUSION: Differentially expressed adrenal proteins in SHRs with live-yang hyperactivity are successfully identified. This approach may lay a foundation for the further investigation of pathogenic mechanisms in hypertension with liver-yang hyperactivity and the mechanisms of PGQYF treatment.

Objective To observe the effect of therapy of soothing liver and subsiding yang on hypothalamic protein expression in hypertensive rats with hyperactivity of liver yang,and to explore its therapeutic molecular mechanism for hypertension.Methods Spontaneous hypertensive rats (SHR)were given gastric gavage of Aconiti Praeparatae Decoction (APD)to induce hypertensive rat model with hyperactivity of liver yang,and SD rats served as the normal control.The treatment group received modified Tianma Gouteng Decoction (TGD,0.1g/mL).Two-dimension gel electrophoresis (2-DE)was used to separate the hypothalamic proteins,and the differential expressed proteins were identified by matrix-associated laser desorption-ionization time-of-flight massspectrometry (MALDI-TOF-MS)and database analysis.Results Hypertensive rat model with hyperactivity of liver yang was established successfully.The irritation degree,in-take water volume and systolic pressure were increased in the model group(P

Objective To explore the molecule mechanisms of migraine with hyperactivity of liver-yang related proteins. Methods Animal model of migraine with hyperactivity of liver-yang was established through electrical trigeminal ganglion stimulation,and by administering orally with Fuzi decoction. The total proteins of splenic lymphocytes in the rats were separated by immobilized pH gradient-based two-dimensional gel electrophoresis. With coomassie blue staining,the 2-DE images were analyzed by PDQuest 7.0 software. Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) and database were used to identify the differential proteins. Result Ten differential spots protein were identified,and they were chloride intracellular channel 1,thioredoxin peroxidase Ⅰ,thioredoxin peroxidase Ⅱ,sequence 7 from patent WO9709348,Rho GDP dissociation inhibitor (GDI) alpha,actin related protein 2/3 complex neurofilament light polypeptide,proteasome subunit beta type and heat shock protein-27,annexin A1. Conclusion These protein may be involved in the development of migraine with hyperactivity of liver-yang. These data provide useful clues for elucidating the mechanisms of migraine with hyperactivity of liver-yang.

A series of valproic acid salicylanilide esters were designed and synthesized based on the principle of prodrug. The structures of the target compounds were confirmed by MS, 1H NMR and 13C NMR. Anti-tumor activities of these compounds against K562, A549, A431 cells in vitro were investigated by MTT assay and SRB assay. The results indicated that the compounds 6h-6j were found to have stronger cell growth inhibitory action than gefitinib, and comparable to niclosamide, which are worth to be intensively studied further.

Objective To explore the molecule mechanisms of ping-gan qianyang therapy on migraine rat model with the hyperactivity of liver-yang.Methods An animal model of migraine with hyperactivity of liver-yang was established through electrical trigeminal ganglion stimulation and administering orally with Fuzi decoction.The total proteins of adrenal#and in the rats were separated by immobilized PH gradient-based two-dimensional gel electrophoresis, and the 2-DE images Was analyzed by PDQuest 7.0 software.Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry(MALDI-TOF-MS)and SWISS-PORT and MSDB database were used to identify differential proteins.Result The well-resolution and reproducible 2-DE patterns of rat adrenal glands in normal group,model group and therapy group were obtained.A total of 8 differentially expressed proteins were identified.Conclusion Ping-gan qianyang therapy may effect on migraine by regulating the expression of proteins related to energy metabolism and ubiquitin.

Objective: To investigate the effects of a Chinese herbal formula for calming liver and suppressing yang on the protein expressions of vascular tissues in spontaneously hypertensive rats (SHRs), and to explore the mechanism of efficacy. Methods: Twenty SHRs were randomly divided into model group and treatment group. Another 10 Wistar-Kyoto rats were selected as a normal control. SHRs in the treatment group were administered with the formula for calming liver and suppressing Yang for 4 weeks. During the course of treatment, blood pressure and heart rates were monitored every week and the ethology of rats, including irritability and rotation endurance was also evaluated. After treatment, thoracic aorta was obtained and its proteins were separated by 2-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and database query. Results: The formula for calming liver and suppressing yang not only decreased the systolic blood pressure and heart rate, but also improved irritability degree and rotation endurance time of SHRs. This experiment had established the 2-DE graph of protein expressions of vascular tissues in SHRs. Compared with the normal group, the expressions of 15 proteins were down-regulated, and 12 proteins were up-regulated in vascular tissues of the model group. The formula for calming liver and suppressing yang treatment up-regulated expressions of 10 proteins in the 15 down-regulated proteins, and down-regulated 8 proteins in the 12 up-regulated proteins in vascular tissues of SHRs. After analysis, 16 obviously differentially expressed proteins were found, and 13 of them were identified. Conclusion: The formula for calming liver and suppressing yang can improve the ethology of SHRs. The mechanism is probably concerned with regulating the protein expressions of vascular tissues.

Objective To study mRNA expression of neuroglobin (NGB) in thalamus of DAI rats and explore the relation between NGB and heed injury. Method 46 male SD rats were randomly divided into four groups. The DAI model was established according to modi-fied Mamamu method. The mRNA expression of NGB in thalamus at different time point after injury was detected by RT-PCR method. All data were analyzed with statistical software. Result The mRNA expression of NGB in thalamus increased obviously from 30 minutes after in-jury while decreased at the 24th hour after injury. But the expression increased again and reached peak at the 48th hour after injury. Conclu-sion The mRNA expression of NGB in thalamus increased after DM. Those changes suggested NGB might participate in the response mech-anism of stress, secondary ischemia and hypoxic brain injury after neuron injury.

Objective To establish two-dimensional electrophoresis(2-DE) profiles with high resolution and reproducibility in analysis of hypothalamuses in the spontaneous hypertension rats(SHR) with hyperactivity of liver-yang to analyze the difference on the total proteins of hypothalamuses between the SHR and normal rats.Methods The total proteins of hypothalamuses in the rats were separated by immobilized pH gradient-based two-dimensional gel electrophoresis.With coomassie blue staining,the 2-DE image was analyzed by PDQuest 7.0 software.Results The average matching rate of the 2-DE images of hypothalamuses in the two kinds rats was 92% with good reproducibility.Proteins were mainly displayed at range of pI3-8,Mr(14.4～75) kD.The average spots in the SHR with hyperactivity of liver-yang and in the normal rats were 777?27 and 780?31 respectively.There were 22 spots of proteins up-regulated more than two times and 25 spots down-regulated more than two times in the SHR with hyperactivity of liver-yang than those of the normal rats.Conclusion There are 22 spots of proteins up-regulated and 25 spots of proteins down-regulated in the SHR with hyperactivity of liver-yang,which may be involved in the development of hyperactivity of liver-yang.

Objective To explore the molecular mechanism of the formulae for calming the liver and suppressing YANG in migraine rat model with syndrome of hyperactivity of the liver-YANG.Methods A rat model of migraine with hyperactivity of liver-YANG was established through electrical trigeminal ganglion stimulation and syndrome of oral administration of Fuzi decoction. The total proteins of the lymphocyte in the rats were separated by immobilized pH gradient-based 2-dimensional gel electrophoresis(2-DE), and the 2-DE image was analyzed by PDQuest 7.0 software. Matrix-assisted laser desorption/ionzation-time of flight mass spectrometry (MALDI-TOF-MS) and the SWISS-PORT and MSDB database were used to identify differential proteins.Results The formulae for calming the liver and suppressing YANG could also improve headache. Well-resolution and reproducible 2-DE patterns of rat lymphocyte from normal, model, and therapy tissues were obtained. Eleven of the total 13 differential protein spots were successfully identified by MALDI-TOF-MS. These proteins were alcohol dehydrogenase 3(ADH3), glycogen phosphorylase, ATP synthase D chain, annexin-3, ubiquitin, neutrophil defensin 4 precursor, melanoma-associated antigen E2, heat shock protein-27, annexin-A1, peroxirdoxin-Ⅱ, MU class glutathione S-transferase (Fragment)(GSH). Conclusion Differences occur in the expression of lymphocyte proteins in migraine rats with syndrome of hyperactivity of liver-YANG after treatment with the formulae for calming the liver and suppressing YANG, and the 11 identified protein spots may be associated with its mechanism.

To observe the efficacy of herbs for calming liver and suppressing liver-yang in treatment of migraine patients with hyperactivity of liver-yang syndrome and to investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of pathogenic mechanisms in migraine with hyperactive liver-yang syndrome and the curative mechanisms of calming liver and suppressing liver-yang treatment.