Effect of Sinisan on BDNF/TrkB， 5-HT/5-HT1AR， and HPA axis in Depression Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Sinisan on the brain-derived neurotrophic factor （BDNF）/tyrosine kinase receptor B （TrKB）， 5-hydroxytryptamine （5-HT）/5-HT1A receptor （5-HT1AR）， and hypothalamus-pituitary-adrenal （HPA） axis in depressed rats， and explore the antidepressant mechanism of Sinisan based on BDNF/TrKB， 5-HT/5-HT1AR， and HPA axis. Method:A total of 120 male Wistar rats were randomly divided into a normal group， a model group， a fluoxetine （0.01 g·kg^-1） group， and low- （1.25 g·kg^-1）， medium- （2.5 g·kg^-1）， and high-dose （5 g·kg^-1） Sinisan groups， with 20 rats in each group. The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group for 21 days. Rats were then treated correspondingly once a day for 21 days by gavage. Those in the normal group and the model group received an equal volume of normal saline. During the intervention， the model rats were stimulated continuously. The depressive state of CUMS model rats was evaluated by sucrose preference test and open field test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of corticotropin-releasing hormone （CRH）， adrenocorticotropic hormone （ACTH）， and corticosterone （CORT） in the plasma and BDNF and 5-HT levels in the hippocampal homogenate. The mRNA expression of hippocampal TrKB， 5-HT1AR， glucocorticoid receptor （GR）， and mineralocorticoid receptor （MR） was detected by real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR）. The protein expression of hippocampal TrKB， 5-HT1AR， GR， and MR was detected by Western blot. The histomorphological changes of the hippocampus were observed by hematoxylin-eosin （HE） staining. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （<italic>P</italic><0.01）， reduced horizontal and vertical scores in the open field test （<italic>P</italic><0.01）， increased plasma content of CRH， ACTH， and CORT （<italic>P</italic><0.01）， declining content of BDNF and 5-HT in the hippocampus （<italic>P</italic><0.01）， dwindled mRNA and protein expression levels of TrKB， 5-HT1AR， and GR （<italic>P</italic><0.01）， elevated mRNA and protein expression of MR （<italic>P</italic><0.01）， and damaged hippocampal neurons revealed by HE staining. Compared with the model group， the groups with drug intervention showed increased sucrose preference rate （<italic>P</italic><0.01） and horizontal and vertical scores in the open field test （<italic>P</italic><0.05， <italic>P</italic><0.01）， decreased content of plasma CRH， ACTH， and CORT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated content of hippocampal BDNF and 5-HT （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA and protein expression levels of hippocampal TrKB， 5-HT1AR， and GR （<italic>P</italic><0.05， <italic>P</italic><0.01）， reduced mRNA and protein expression levels of hippocampal MR （<italic>P</italic><0.05， <italic>P</italic><0.01）， and recovered hippocampal neurons as revealed by HE staining. Conclusion:Sinisan can exert a significant antidepressant effect by increasing hippocampal BDNF and 5-HT content， up-regulating TrKB， 5-HT1AR， and GR mRNA and protein expression， down-regulating MR mRNA and protein expression， inhibiting HPA axis hypertrophy， and enhancing the regeneration and repair of hippocampal neurons.

Effect of Zuoguiwan on Wnt/β-catenin Signaling Pathway in Ovariectomized Osteoporosis Model Rats / 中国实验方剂学杂志

Objective:To observe the effect of Zuoguiwan on bone metabolism and Wnt/<italic>β</italic>-catenin signaling pathway in ovariectomized osteoporotic rats model， and to explore the molecular biological mechanism of Zuoguiwan in the prevention and treatment of osteoporosis. Method:The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy， 60 female SD rats were randomly divided into sham operation group， model group， positive group （estradiol valerate tablet 0.05 mg·kg^-1·d^-1） and low， middle and high dose groups of Zuoguiwan （5.5，11，22 g·kg^-1·d^-1）.After successful establishment of the model in the 13^th week， intragastric administration （<italic>ig</italic>） was given once a day for a total of 12 weeks. After administration， the histomorphological changes of femur in rats were observed by hematoxylin-eosin （HE） staining， the bone mineral density （BMD） and bone mineral content（BMC） of femur were measured by dual energy X-ray apparatus， and the biomechanical properties of bone were measured by MTS Acumen3 biomechanical testing system. The contents of bone alkaline phosphatase （BALP）， bone glaprotein（BGP），estradiol （E₂） ，and tartrate-resistant acid phosphatase （TRAP）， type Ⅰ procollagen N-terminal propeptide （PINP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein level of Wnt2，<italic>β</italic>-catenin，low density lipoprotein related receptor protein 5 （LRP5） and the phosphorylation level of glycogen synthase kinase-3<italic>β</italic>（GSK-3<italic>β</italic>） in rat tibia. Result:Compared with sham operation group， the maximum load and stiffness of BMD，BMC， in the model group decreased significantly（<italic>P</italic><0.01）， the contents of E₂ and PINP in serum decreased significantly（<italic>P</italic><0.01）， the content of BALP，BGP，TRAP increased significantly（<italic>P</italic><0.01）， the expression levels of Wnt2，p-GSK-3<italic>β </italic>Ser9，LRP5 and <italic>β</italic>-catenin protein in bone tissue decreased significantly（<italic>P</italic><0.01）， the trabecula of femur became thinner and thinner， the number of bone trabeculae decreased. Compared with model group， the maximum load and stiffness of BMD，BMC， in estradiol group and Zuoguiwan group were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the contents of serum E₂ and PINP were significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01）， the content of BALP，BGP，TRAP was significantly decreased （<italic>P</italic><0.01）， and the expression level of Wnt2，p-GSK-3<italic>β</italic> Ser9，LRP5， <italic>β</italic>-catenin protein in bone tissue was significantly increased （<italic>P</italic><0.05，<italic>P</italic><0.01） ， the trabeculae of femur became thicker， the number increased， the structure was basically clear. Conclusion:Zuoguiwan has a certain preventive and therapeutic effect on osteoporosis in ovariectomized rats， and its mechanism may be related to increasing the level of estrogen， activating Wnt/<italic>β</italic>-catenin signaling pathway， up-regulating the expression of Wnt2 and LRP5 protein， inhibiting the activity of GSK-3<italic>β</italic>， reducing the degradation of <italic>β</italic>-catenin， coordinating the dynamic coupling balance between bone formation and bone resorption， correcting the disorder of bone metabolism and improving bone morphology.

Research Progress of ZHANG Zhong-jing's Classical Formulae in Treatment of Depression / 中国实验方剂学杂志

Depression is a kind of emotional and mental disorder， which is related to many pathogenic factors， such as abnormal metabolism of monoamine neurotransmitters， immune inflammatory reaction， neuroendocrine disorder and so on. it has the characteristics of high disability rate and high recurrence rate， which is seriously harmful to human health. It brings huge economic burden to patients and their families. At present， the commonly used antidepressants in clinic are monoamine oxidase inhibitors， tricyclic antidepressants and selective 5-hydroxytryptamine reuptake inhibitors. Long-term use causes adverse reactions such as cardiovascular， urinary and digestive dysfunction. The multi-target， multi-pathway and multi-mechanism of traditional Chinese medicine has played a great role in the treatment and rehabilitation of depression. At the same time， traditional Chinese medicine has gradually become a hot spot in the research and development of antidepressants because of its small side effects and good drug compliance. Especially the ZHANG Zhong-jing's classical formulae with precise medication and rigorous prescription has unique advantages in the treatment of depression. For thousands of years， it has been used clinically by countless doctors in the treatment of various types of depression， with definite curative effects and few side effects. In recent years， clinical research， experimental research， and pharmacological research around ZHANG Zhong-jing's classical formulae for depression have been continuously expanded and deepened. This article reveals the rules of medication of the treatment of depression with ZHANG Zhong-jing's classical formulae from three aspects of Bupleurum class prescription， Gardenia class prescription， and other prescriptions， which is reflected in the study on the composition of prescription， the etiology， and pathogenesis and the symptoms of the treatment. Integrating and classifying ZHANG Zhong-jing's classical formulae's experience in the treatment of depression， mainly expounded from two aspects， clinical research and pharmacological research， summarizing the research perspective and progress of Zhongjing prescription medicine in the treatment of depression in recent years， to excavate， inherit and develop ZHANG Zhong-jing's classical formulae， and provide experience and reference for the treatment of depression from multiple angles and ideas.

Effect of Chaihu Jia Longgu Mulitang on Signaling Pathway of PI3K/Akt/GSK3β/β-catenin in Hippocampus Tissue of Rats with Depression / 中国实验方剂学杂志

Objective:To study the effect of Chaihu Jia Longgu Mulitang on phosphatidylinositol-3-kinases （PI3K）/protein kinase B （Akt）/glycogen synthase kinase 3β （GSK3β）/β-catenin signaling pathway of hippocampus in rats with depression. Method:A total of 120 SD rats were randomly divided into normal group，model group， and low， middle and high-dose Chaihu Jia Longgu Mulitang groups（3.25，6.5，13 g·kg-1）， and fluoxetine group， with 20 rats in each group. Except normal group， the depression model was prepared through chronic unpredictable mild stimulation（CUMS）. The normal group and the model group were given normal saline with 6.5 g·kg-1 by gavage. Chaihu Jia Longgu Mulitang groups were intragastrically given corresponding herbal drugs 3.75，6.5，13 g·kg-1， while fluoxetine group was intragastrically given fluoxetine 10 mg·kg-1 for 21 days， once a day. Then the depressive behaviors of rats were observed by sucrose preference test （SPT） and forced swimming test （FST）. Western blot was used to detect the protein expressions of PI3K，Akt，GSK3β and phosphorylation level. Result:Compared with normal group，the sucrose preference index was decreased significantly，while the immobility time in FST was increased significantly（P<0.01）， the protein expressions of PI3K， p-PI3K p110， p-PI3K p85 were decreased significantly （P<0.01）， and expressions of Akt， p-Akt Thr308，p-Akt Ser473， p-GSK3β Ser9 and β-catenin were decreased significantly（P<0.01）， while the level of GSK3β， p-GSK3β Tyr216 were increased significantly in model group（P<0.05，P<0.01）. Compared with model group，Chaihu Jia Longgu Mulitang could increase sucrose preference index and decrease the immobility time in FST（P<0.01）， the protein expressions of PI3K p110 and PI3K p85 was increased significantly （P<0.01）， levels of Akt Thr308，Akt Ser473， p-GSK3β Ser9， β-catenin were increased significantly （P<0.01）， whereas levels of GSK3β， and GSK3β Tyr216 were decreased significantly. Conclusion:Chaihu Jia Longgu Mulitang could increase protein expression and activity of PI3K in rat hippocampus， activate Akt， inhibit GSK3β kinase activity and prevent β-catenin from degradation， so as to increase PI3K/Akt pathway activity in rat hippocampus， and protect hippocampal neurons.

Effect of Modified Suanzaoren Tang on Expression of Glutamate Receptor in Hippocampus of Chronic Restraibt Stress Depression Model Rat / 中国实验方剂学杂志

Objective:To study the effect of modified Suanzaoren Tang on the expression of excitatory amino acids receptor（EAARs） in hippocampus of rats with chronic depression， and to explore the anti-depressant mechanism of modified Suanzaoren Tang based on excitatory amino acids receptor. Method:Sixty SD rats were randomly divided into normal group，model group，and low，middle and high-dose modified Suanzaoren Tang groups，and ketamine group，with 10 rats in each group．Except normal group，the depression model of rats was prepared by using chronic restraint stress（CRS）.The normal group and model group were intragastrically（ig） given normal saline．the modified Suanzaoren Tang groups were intragastrically given corresponding herbal drugs 6，12，24 g·kg-1， ketamine group group were given ketamine 0.015 g·kg-1 through intraoeritoneal injection，for 21 days，once a day．Then the depressive behaviors of rats were observed by Morris water maze and novelty feeding experiment.Western blot was used to detect the levels of DAR1，NMDAR2A，NMDAR2B，GluR1，mGluR1，CaMKⅡα and CaMKⅡβ protein expression in rat hippocampus tissue. Result:Compared with normal group，the time of novel ingestion and escape latencywere prolonged significantly（P<0.01）， and the time of space exploration was shortened significantly（P<0.01）.The levels of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ expression were increased significantly（P<0.01），while the levels of GluR1 and CaMKⅡα expression were decreased significantly（P<0.01）in model group. Compared with model group，the time of novel ingestion and escape latency were shortened significantly （P<0.01）， and the time of space exploration was prolonged significantly（P<0.01）.The levels of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ protein expression were decreased significantly（P<0.01），but the levels of GluR1 and CaMKⅡα expression were increased decreased significantly（P<0.01）in middle and high-dose modified Suanzaoren Tang groups. Conclusion:Modified Suanzaoren Tang can improve the behavior of chronic depression rats effectly. Its mechanism may be related with reduction the expression of NMDAR1，NMDAR2A，NMDAR2B，mGluR1 and CaMKⅡβ protein ，increase the expression of GluR1and CaMKⅡα protein.

Effect of Modified Xiao Chaihutang on Expression of EAATs and VGLUTs in Hippocampus of Chronic Restraibt Stress Depression Model Rat / 中国实验方剂学杂志

Objective:To study the effect of modified Xiao Chaihutang on the expressions of excitatory amino acid transporters（EAATs） and vesicle glutamate transporters（VGLUTs）in hippocampus of rats with chronic depression， in order to explore the anti-depressant mechanism of modified Xiao Chaihutang based on glutamate transport. Method:A total of 120 SD rats were randomly divided into normal group， model group， and low， middle and high-dose modified Xiaochaihutang groups （6.5， 13， 26 g·kg-1） and riluzole group， with 20 rats in each group．Except normal group， the depression model of rats was prepared through Chronic restraint stress（CRS）. The normal group and the model group were intragastrically （ig） given normal saline. The modified Xiao Chaihutang groups were intragastrically given corresponding herbal drugs （6.5， 13， 26 g·kg-1）， and the Riluzole group was given Riluzole 20 mg·kg-1 through intraoeritoneal injection for 21 days， once a day. Then the depressive behaviors of rats were observed by forced swimming test （FST） and tail suspension test （TST）. The level of glutamic acid （Glu） in rats hippocampus was determined by high performance liquid chromatography （HPLC）. The mRNA expressions of EAAT1， EAAT2 and EAAT3 in hippocampus were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）method. Western blot was used to detect the protein expressions of EAAT1， EAAT2， EAAT3， VGLUT1 and VGLUT2 in rat hippocampus tissue. Nissl staining was used to observe the morphology of hippocampal neurons in rats. Immunohistochemical（IHC）S-P method were used to detect the location expressions of EAAT1， EAAT2 and NeuN proteins in rat hippocampal CA1 region tissue. Result:The immobility times in FST and TST were increased significantly（P<0.01）， the mRNA and protein expressions of EAAT1，EAAT2，EAAT3 were decreased significantly （P<0.01）， and as well as the expressions of VGLUT1 and NeuN were decreased significantly（P<0.01）， while the level of Glutamate and the expression of VGLUT2 were increased significantly（P<0.01） in model group， compared with normal group. Compared with model group，the immobility times in FST and TST were decreased significantly（P<0.05， P<0.01）， mRNA and protein expressions of EAAT1，EAAT2，EAAT3 were increased significantly（P<0.01）， and expressions of VGLUT1 and NeuN were increased significantly（P<0.01）. However， the level of Glutamate and the expression of VGLUT2 were decreased significantly（P<0.01）， and the damage of hippocampal neurons in rats was mild in middle and high-dose modified Xiao Chaihutang groups. Conclusion:Modified Xiao Chaihutang has an anti-depressive effect. Its mechanism may be related to its up-regulation of expressions of EAAT1， EAAT2， EAAT3 genes and VGLUT1 protein in the hippocampus of depression model rats.

Regulatory Effect of Modified Erchentang on Levels of Lymphokines Relating to Th1,Th2 and Th9 Cells and Expressions of IL-4R1/IL-13RA1 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.

Mechanism of Modified Erchentang on Expression of CXCL8-CXCR1/2 Axle Genes in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To observe the effect of modified Erchentang on the expression of CXC chemokine ligand (CXCL) 8-CXC chemotaxis factor receptor (CXCR) 1/2 genes in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), in order to explore the anti-inflammatory molecular mechanism of Erchentang on COPD. Method:Forty SD rats were randomly divided into normal group, model group, Jizhi syrup group and modified Erchentang group. COPD models in rats were prepared by cigarette smoke and dripping lipopolysaccharide (LPS) in the trachea. After modeling, normal and model groups were intragastrically given normal saline solution, Jizhi syrup group was given Jizhi syrup（10 g·kg-1），and modified Erchentang group was given intragastrically corresponding herbal drugs (10 g·kg-1) for 14 days. The levels of chemokines CXCL1, CXCL8 were detected by enzyme-linked immunosorbent assay in rat bronchoalveolar lavage fluid (BALF). The mRNA expressions of CXCL8, CXCR1 and CXCR2 were detected by quantitative real time PCR (Real-time PCR). Western blot was used to detect the levels of CXCL8, CXCR1 and CXCR2 protein, the pathological changes of lung tissues were observed by hematoxylin-eosin(HE) staining,and immunohistochemistry (IHC) method was used to detect the expressions of CXCL8, CXCR1 and CXCR2 protein in the lung tissue of all the groups. Result:The levels of chemokines CXCL1, CXCL8 in rats BALF were increased significantly (P<0.01), the expressions of CXCL8，CXCR1 and CXCR2 mRNA and protein were increased significantly (P<0.05, P<0.01) in model group compared with normal group. Compared with model group, the expressions of CXCL8, CXCR1 and CXCR2 mRNA and protein were decreased significantly (P<0.05), and the levels of chemokines CXCL1, CXCL8 in rats BALF were decreased significantly (P<0.01) in modified Erchentang. Conclusion:Modified Erchentang has an anti-inflammatory effect on COPD. The mechanism may be related to inhibiting the expressions of CXCL8, CXCR1, CXCR2 mRNA and protein, and reducing the release of chemokines CXCL1, CXCL8.

Signal Pathways Relating to Prevention and Treatment of Airway Remodeling in Chronic Obstructive Pulmonary Disease with Traditional Chinese Medicine / 中国实验方剂学杂志

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with a high morbidity, disability and mortality. At the same time, COPD is always accompanied by pulmonary hypertension, pulmonary fibrosis, chronic pulmonary heart disease, right heart failure and other common serious complications. All of these cause serious financial burden for the family of patients. Airway remodeling plays an important role in the pathogenesis of COPD. It is the progressive development of airflow restriction that induces the main symptoms of COPD, such as cough, asthma and depression. Therefore, it is of great research value to explore the intervention of traditional Chinese medicine(TCM) in the development of COPD by alleviating airway remodeling. Studies have shown that multiple signaling pathways can induce progressive airway remodeling, and the therapeutic effect of TCM has been frequently confirmed by experimental studies. TCM often has a therapeutic effect on COPD through multi-target and multi-channel mediation. This paper mainly includes five signaling pathways that traditional Chinese medicine can intervene COPD airway remodeling, namely matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinase (TIMPs), transforming growth factor (TGF)-beta 1/Smads, RhoA/Rho-associated kinase (ROCK), vascular endothelial growth factor (VEGF)/b-fibroblast growth factor (b-FGF) and nuclear factor (NF)-κB. This paper briefly reviews the research progress of these five signaling pathways, and discusses other signaling pathways that may be involved, in order to provide reference and ideas for future experimental research.

Mechanism of Modified Erchentang on Signaling Pathway of TLR4/MyD88/NF-κB in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective: To study the effect of modified Erchentang on expressions of Toll-like receptor 4 (TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB (NF-κB) genes in the lung tissue homogenate of rats with chronic obstructive pulmonary disease (COPD). Method: Forty SD rats were randomly divided into normal group, model group, modified Erchentang group and EVP4593 (NF-κB inhibitor) group. Rat COPD models were prepared through cigarette smoke and tracheal dripping with lipopolysaccharide (LPS). After the modeling, normal and model groups were intragastrically given normal saline solution, EVP4593 group was given EVP4593(1 mg · kg-1) through subcutaneous injection, and modified Erchentang group was given corresponding herbal drugs intragastrically (10 g · kg-1) for 14 days. The levels of high mobility group box 1(HMGB1), chemokines CXCL-2, CXCL-3 and monocyte chemoattractant protein-1 (MCP-1) in rats serum were detected by enzyme-linked immunosorbent assay in rats serum. The expressions of Toll-like receptors 4(TLR4), myeloid differentiation factor (MyD88) and nuclear factor-κB p65 (NF-κB p65) mRNA were detected by Real-time fluorescence quantitative PCR (Real-time PCR) method. Western blot were used to detect the levels of TLR4, MyD88, NF-κB p65 and p-NF-κB p65 protein. Immunohistochemistry (IHC) method was used to detect the localization and expressions of TLR4, MyD88 and p-NF-κB p65 protein in the lung tissue. Result: The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 were increased significantly (PPκB p65 mRNA and protein were decreased significantly (PConclusion: Modified Erchentang may inhibit the inflammatory response of COPD effectively. The mechanism may be related to the inhibition of the expressions of the signal molecule genes involved in the TLR4/MyD88/NF-κB pathway and the reduction of the release of HMGB1, CXCL-2, CXCL-3 and MCP-1.

[Effects of Scutellaria Barbata on VEGF Expression in K562 Cells].

OBJECTIVE: To investigate the anti-angiogenesis effect of Scutellaria barbata extract(SBE) on chronic myeloid leukemia(CML) K562 cell line in vitro. METHODS: The proliferating activity after treating K562 cells with 0.5,1.0,2.0 and 4.0 g/ml SB for 24, 36, 48 hours were assessed by MTT assay. The level of vascular endothelial growth factor(VEGF) in the culture supematant of K562 cells was determined by ELISA; and the expression of VEGF mRNA was detected by RT-PCR. RESULTS: MTT assay showed that SBE could inhibit the proliferation of K562 cells in a dose-dependent manner (r=0.56); ELISA displayed that the concentration of VEGF in K562 cells in blank-control group was most high; after intervention of K562 cells by SBE (0.5,1.0,2.0 and 4.0 g/ml) for 48 h, the concentration of VEGF decreased, the comparison between different groups showed significant differences (P<0.05); after treatment with SBE for 48 h, the expression of VEGF mRNA in K562 cells decreased, the gray scale ratio of target gene/ß-actin declined, and the difference between various groups was statistically significant (P<0.05). Conclution: SBE can inhibit K562 cell proliferation, its action mechanism may related with the VEGF level concentration in K562 cells and down-regulation of VEGF mRNA expression.

Effects of Tongguan Capsule on post-myocardial infarction ventricular remodeling and cardiac function in rats.

OBJECTIVE: To observe the effects of Tongguan Capsule (TGC) on post-myocardial infarction ventricular remodeling and heart function in rats. METHODS: A rat model of acute myocardial infarction (AMI) was established by coronary ligation. Experimental rats were randomized to 4 groups including three model groups (Group A: captopril 5 mg/kg * day, n=7; Group B: TGC 10 g/kg * day, n=7; and Group C: placebo, n=8), and a sham-control group (Group D: blank control, n=6). Animals were treated for 4 weeks. The cardiac function of rats was assessed at the end of the experiment based on left ventricular ejection fraction (LVEF) and left ventricular short axis fractional shortening (LVFS) detected by colored echocardiography; meanwhile, the condition of ventricular remodeling was observed through the levels of left ventricular mass (LVM), plasma aldosterone (ALD), myocardial angiotensin II (Ang II) and myocardial collagen measurements. RESULTS: At the end of the experiment, LVEF and LVFS in Group A and B were improved significantly, while those in Group C were unchanged, the LVEF in Group A, B, C, and D was 0.57+/-0.46, 0.61+/-0.08, 0.36+/-0.55 and 0.76+/-0.02, respectively; and their LVFS was 0.31+/-0.52, 0.34+/-0.04, 0.23+/-0.57 and 0.45+/-0.03, respectively. The difference was statistically significant when comparing the two indexes in Group A and B with those in Group C and D (P<0.05). LVM, levels of plasma ALD and myocardial Ang II were lower in Group A and B than in Group C, but a comparison between Group A and B showed an insignificant difference in lowering LVM and ALD, while the lowering of Ang II was more significant in Group B than in Group A (754.7 +/- 18.7 pg/mL vs 952.6+/-17.6 pg/mL, P<0.05). Morphological examination showed that in Group A and B the swollen myocardial cells had shrunk, with regularly arranged myocardial fibers and decreased collagen proliferation, but the improvements in Group B were more significant. CONCLUSION: TGC could markedly improve the post-infarction ventricular remodeling and cardiac function in rats, showing that the efficacy was better than or equal to that of captopril.