Mechanisms of Compound Kushen Injection for the treatment of bladder cancer based on bioinformatics and network pharmacology with experimental validation / 中国天然药物

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.

Study on mechanism of Compound Kushen Injection inducing autophagy to promote apoptosis of bladder cancer cells / 中草药

Objective: To investigate the effect of Compound Kushen Injection on proliferation, apoptosis, and autophagy of bladder cancer T24 cells, and to explore the molecular mechanisms involved, and provide theoretical basis for Compound Kushen Injection in clinical treatment of bladder cancer. Methods: The effect of Compound Kushen Injection on proliferation of bladder cancer cells was detected by CCK-8 method. Flow cytometry was used to detect the effect of Compound Kushen Injection on bladder cancer cell apoptosis. MDC staining was used to detect the effect of Compound Kushen Injection on autophagy of bladder cancer cells. Western blotting and immunofluorescence experiments were used to detect the effect of Compound Kushen Injection on key protein involved in apoptosis and autophagy of bladder cancer cells. Results: Compound Kushen Injection effectively inhibited the proliferation of bladder cancer T24 cells. Compound Kushen Injection induced bladder cancer cells to undergo apoptosis and autophagy. The results of Western blotting and immunofluorescence experiments showed that as the concentration of Compound Kushen Injection increased, the expressions of Bcl-2 and P62 in bladder cancer T24 cells were gradually decreased, and the expressions of Bax, cleaved-Caspase 3, Beclin1, and LC3Ⅱ were increased (P < 0.05), but Bcl-2/Bax ratio was decreased (P < 0.05). Conclusion: Compound Kushen Injection can inhibit the proliferation of bladder cancer T24 cells, regulate autophagy of bladder cancer T24 cells, and induce bladder cancer T24 cell apoptosis. Key words:

The prevalence and risk factors of metabolic syndrome in Chinese population based on the multi center cross-sectional survey / 中华疾病控制杂志

Objective To understand the prevalence and risk factors of metabolic syndrome (MS) among different ethnic groups. Methods A multicenter cross-sectional survey was conducted. Subjects were selected by multistage stratified random sampling. Physical examination and laboratory testing were performed to collect MS related indicators, and the prevalence was standardized by the 6th general survey data. Further multivariate and logarithmic linear model methods were applied to analyze the risk factors and interaction. Results The overall prevalence of MS was 19.58%. The highest prevalence of MS was in Korean, followed by Han, while the lowest was in Kazakh. The rates of MS, overweight and obesity were higher in men than those in women, and increased along with age. Multivariate analysis result showed that the odds ratio (OR) of female to male was 0.556, and aging increased the risk of MS. The OR of central obesity was 2.765, and would reach to 4.259 when the waist-to-body ratio was over 0.52. The logarithmic linear model showed that the overweight/obesity, hyperglycemia, hypertension and dyslipidemia had independent effects on the risk of MS. Also, there were interactions in the four indicators. Conclusions The incidence of MS is high and the positive interaction between the overweight/obesity, hyperglycemia, hypertension and dyslipidemia is observed, making MS a common crisis to clinical and public health. In order to prevent and control MS, and to reduce the risk of cardiovascular and cerebrovascular diseases and diabetes, early screening of MS should be strengthened and lifestyle intervention should be carried out.

Effects of stachydrine hydrochloride on experimental acute cerebral in-farction in rats / 中国病理生理杂志

AIM:To observe the therapeutic effect of stachydrine hydrochloride on experimental acute cerebral infarction in rats and to explore the underlying mechanisms .METHODS:SD rats ( n=75) were randomly divided into 5 groups:sham group, cerebral infarction model group , and stachydrine hydrochloride (10 mg/kg, 20 mg/kg and 40 mg/kg) treatment groups .After the establishment of cerebral infarction model , the rats were given stachydrine hydrochloride at dose of 10 mg/kg, 20 mg/kg or 40 mg/kg by gavage daily for 14 d.The impairment of neurological function in each group was scored .The cerebral infarction volume and brain water content were measured .Moreover , the protein levels of β-cate-nin, cyclin D1, glycogen synthase kinase 3β(GSK-3β) and p-GSK-3βin the brain tissues were detected by Western blot . RESULTS:Compared with cerebral infarction group , the score of neurological function impairment , cerebral infarction volume and brain water content were significantly decreased in stachydrine hydrochloride treatment groups .In addition , the protein levels of β-catenin, cyclin D1 and p-GSK-3βwere markedly increased after stachydrine hydrochloride treatment . CONCLUSION:Stachydrine hydrochloride protects against experimental acute cerebral infarction through activation of Wnt/β-catenin signaling pathway .

Effects of stachydrine hydrochloride on experimental acute cerebral in-farction in rats / 中国病理生理杂志

AIM:To observe the therapeutic effect of stachydrine hydrochloride on experimental acute cerebral infarction in rats and to explore the underlying mechanisms .METHODS:SD rats ( n=75) were randomly divided into 5 groups:sham group, cerebral infarction model group , and stachydrine hydrochloride (10 mg/kg, 20 mg/kg and 40 mg/kg) treatment groups .After the establishment of cerebral infarction model , the rats were given stachydrine hydrochloride at dose of 10 mg/kg, 20 mg/kg or 40 mg/kg by gavage daily for 14 d.The impairment of neurological function in each group was scored .The cerebral infarction volume and brain water content were measured .Moreover , the protein levels of β-cate-nin, cyclin D1, glycogen synthase kinase 3β(GSK-3β) and p-GSK-3βin the brain tissues were detected by Western blot . RESULTS:Compared with cerebral infarction group , the score of neurological function impairment , cerebral infarction volume and brain water content were significantly decreased in stachydrine hydrochloride treatment groups .In addition , the protein levels of β-catenin, cyclin D1 and p-GSK-3βwere markedly increased after stachydrine hydrochloride treatment . CONCLUSION:Stachydrine hydrochloride protects against experimental acute cerebral infarction through activation of Wnt/β-catenin signaling pathway .

Antioxidative effects of cysteinyl leukotriene receptor antagonists montelukast and HAMI 3379 on ischemic injury in rat cortical neurons in vitro / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro.</p><p><b>METHODS</b>Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/R）or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2R，and the effects were observed.</p><p><b>RESULTS</b>ROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1μmol/L moderately decreased OGD/R-induced ROS production (P<0.05). Montelukast mildly attenuated OGD/R-induced MMP depolarization (P<0.05)，but HAMI 3379 had no effect. H2O2 reduced neuronal viability and increased LDH release, namely inducing neuronal injury. Montelukast and HAMI 3379 at 0.1-1μmol/L moderately attenuated H2O2-induced neuronal injury (P<0.05). However, both CysLT1R siRNA and CysLT2R shRNA did not significantly affect the responses mentioned above.</p><p><b>CONCLUSION</b>In ischemic neuronal injury, montelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.</p>

Zileuton, a 5-lipoxygenase inhibitor, attenuates mouse microglial cell-mediated rotenone toxicity in PC12 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the effect of a selective inhibitor of 5-lipoxygenase (5-LOX) zileuton on microglia-mediated rotenone neurotoxicity.</p><p><b>METHODS</b>The supernatant from different concentrations of rotenone-stimulated mouse microglia BV2 cells was used as the conditioned media (CM) for PC12 cells. The viability of PC12 cells was determined by MTT assay and lactate dehydrogenase (LDH) release. Cell death was observed by LDH release and double fluorescence staining with Hoechst/propidiumiodide (PI). The effect of zileuton on microglia-mediated rotenone toxicity was evaluated by the above methods.</p><p><b>RESULTS</b>Rotenone at 1-10 nmol/L was nontoxic to PC12 cells directly. However, the CM from BV2 cells that were treated with rotenone (1-10 nmol/L) resulted in toxicity of PC12 cells. The BV2 CM which stimulated with rotenone (1-10 nmol/L) induced morphological changes, reduced cell viability, and increased LDH release and cell necrosis in PC12 cells. Pretreatment of BV2 cells with the 5-LOX inhibitor zileuton (0.01-1 μmol/L) protected PC12 cells from the microglia-mediated rotenone toxicity.</p><p><b>CONCLUSION</b>The 5-LOX inhibitor zileuton effectively attenuates microglia-mediated rotenone toxicity in PC12 cells. These results suggest that 5-LOX pathway may be involved in neuronal death induced by microglial inflammation.</p>

Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate whether cysteinyl leukotriene receptor 1 (CysLT₁ receptor) is involved in rotenone-induced injury of PC12 cells.</p><p><b>METHODS</b>After 24 h treatment with rotenone or with rotenone and the CysLT₁ receptor antagonist montelukast, PC12 cell viability was determined by the colorimetric MTT reduction assay. After PC12 cells were treated with various concentrations of rotenone for 24 h or with 3 μmol/L rotenone for various durations, the expression of CysLT(1) receptor was determined by Western blotting, and its intracellular distribution was detected by immunocytochemistry.</p><p><b>RESULTS</b>Rotenone (0.3-30 μmol/L) induced PC12 cell injury; this injury was significantly attenuated by montelukast at 1 and 5 μmol/L.The expression of CysLT(1) receptor increased after rotenone treatment at 1-10 μmol/L, or at 3 μmol/L for 3 and 24 h. Rotenone caused concentration-and time-dependent translocation of CysLT₁ receptor from the nucleus to the cytosol.</p><p><b>CONCLUSION</b>Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells.</p>

Rotenone-induced changes of cysteinyl leukotriene receptor 1 expression in BV2 microglial cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To prepare and identify a polyclonal antibody (pAb) against (mouse) cysteinyl leukotriene receptor 1 (CysLT(1)) and to investigate the changes of CysLT(1) receptor expression in BV2 microglial cells after rotenone treatment.</p><p><b>METHODS</b>Rabbits were immunized with KLH-coupled CysLT(1) peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by ELISA method, and the specificity of the pAb was tested by antigen blockade. After BV2 cells were treated with rotenone (0.01-1 μmol/L) for 24 h, the expression of CysLT(1) was determined by immunostaining, Western blotting and RT-PCR.</p><p><b>RESULT</b>The pAb showed a titer of 1/32728, and was not cross-reacted with antigens of CysLT(2) receptor and GPR17. Immunostaining, Western blotting and RT-PCR analysis showed the expression of CysLT(1) receptor in BV2 microglia. Rotenone at 1μmol/L significantly induced an increased expression of CysLT(1) receptor.</p><p><b>CONCLUSION</b>The prepared CysLT(1) receptor polyclonal antibody has a high titer and high specificity to meet testing requirements of Western blotting and immunostaining; CysLT(1) is associated with rotenone-induced injury of BV2 microglial cells.</p>

5-lipoxygenase is involved in rotenone-induced injury in PC12 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine whether 5-lipoxygenase (5-LOX) is involved in rotenone-induced injury in PC12 cells, which is a cell model of Parkinson disease.</p><p><b>METHODS</b>After rotenone treatment for various durations, cell viability was determined by colorimetric MTT reduction assay, and 5-LOX translocation was detected by immunocytochemistry. The effect of 5-LOX inhibitor zileuton was also investigated.</p><p><b>RESULT</b>Rotenone (0.3-30 μmol/L) induced PC12 cell injury, and zileuton (3-100 μmol/L) attenuated this injury. Rotenone also time-and concentration-dependently induced 5-LOX translocation into the nuclear envelope, and zileuton (1-30 μmo/L) significantly inhibited rotenone-induced 5-LOX translocation.</p><p><b>CONCLUSION</b>5-LOX is involved in rotenone-induced injury in PC12 cells, and 5-LOX inhibitor zileuton can reduce rotenone-induced 5-LOX activation and cell injury.</p>

Yolk sac tumor of mouth floor / 华西口腔医学杂志

Yolk sac tumor (endodermal sinus tumor) is a malignant germ cell tumor which usually arise in gonads. It is rare occurring in the oral cavity. Here, a yolk sac tumor of mouth floor was reported and relevant literatures were reviewed.

Preparation and identification of a polyclonal antibody against novel cysteinyl leukotriene receptor GPR17 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To prepare and identify a polyclonal antibody (pAb) against GPR17, a novel cysteinyl leukotriene receptor.</p><p><b>METHODS</b>Rabbits were immunized with KLH-coupled GPR17 peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. GPR17 tissue distribution was detected by Western blot with the pAb.</p><p><b>RESULTS</b>The pAb showed a titer as high as 1:16 364,and was not cross-reacted with the antigens of CysLT(1) and CysLT(2) receptors. A higher expression of GPR17 in the rat brain and heart was detected using the newly prepared pAb. The molecular weigh of GPR17 protein was about 43 kD.</p><p><b>CONCLUSION</b>The prepared GPR17 pAb has high sensitivity and specificity,and can be used in Western blot for detecting GPR17.</p>

Preparation and identification of polyclonal antibody against cysteinyl leukotriene receptor 2 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To prepare and identify a polyclonal antibody against cysteinyl leukotriene receptor (CysLT(2)receptor).</p><p><b>METHODS</b>Rabbits were immunized with KLH-coupled CysLT(2) receptor peptide to prepare the polyclonal antibody (pAb). The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. The tissue distribution of CysLT(2) receptor was detected by Western blot and immunohistochemistry with the prepared pAb.</p><p><b>RESULT</b>The pAb showed a titer higher than 1/1047296, and was specific to CysLT(2) receptor, without cross-reaction with the antigens of CysLT(1) receptor and GPR17. A higher expression of CysLT(2) receptor in kidney, brain and lung of rats and mice was detected by Western blot analysis using the prepared pAb. The molecular weight of CysLT(2) receptor protein was about 40 kD. Immunohistochemical examination showed that CysLT(2) receptor was expressed mainly in the neuron, and partly in astrocytes in rat brain.</p><p><b>CONCLUSION</b>The prepared CysLT(2) receptor pAb has high sensitivity and specificity, and can be used in Western blot and immunohistochemistry.</p>

A clinical study of fungal infection in burn patients / 中华烧伤杂志

<p><b>OBJECTIVE</b>To address the features of the fungal infection after burn injury in clinic.</p><p><b>METHODS</b>Three thousand nine hundred and nine burn patients admitted to our institute from Jan. 2003 to Dec. 2006 were involved in this study. Two thousand two hundred and seventy-one samples were harvested for fungal detection by culture from 467 patients suspected to be infected by fungi based on their clinic manifestations. The collected samples included wound tissue, blood, urine, stool, sputum, catheters and others. The antibiotic sensitivity of the identified fungi were determined by routine method. When same kind of fungus was found from different samples taken from one patient, it was recorded as one positive sample. The samples were ranked in an ascending order as wound secretion, stool, urine, sputum and bronchial alveolar lavage fluid, arteriovenous catheter or urinary catheter, blood. Only the positive sample of the highest rank source was recorded as the positive strain of fungus from this particular patient.</p><p><b>RESULTS</b>It was found 61 fungal positive samples from the 2271 samples collected. Out of 467 patients, 38 strains of fungi were detected from 36 burn patients during the investigated period, the incidence was 0.92% (36/3909). The most three commonest types among the identified 38 strains of fungi were Candida tropicalis (42.1%), Candida albicans (31.6%) and Candida famata (T. Famata, 10.5%). The drug sensitivity tests demonstrated that most of the strains detected in this investigation, with the exception of candida glabrata, were sensitive to most of the routine antimycotics agents such as Amphotericin B, Fluconazole, and Itraconazole etc. Among the 36 fungus positive patients, in 18 patients the burn area exceeded 80% TBSA, 12 patients with 50%-79% TBSA, 4 patients with 30%-49% TBSA, and in 2 patients the burn area was smaller than 30% TBSA. It was found most of the fungal infections (77.78%) occurred 2 weeks after burn injury, and 8 of the 36 fungus-infected patients died (the mortality was 22.22%). Conclusions Further examinations are necessary to confirm the diagnosis in burn patients suspected to have fungal infection. Once fungal infections are confirmed, antimycotic therapy must be started immediately.</p>

5-Lipoxygenase/cysteinyl leukotriene pathway is not involved in injury of rat C6 glioma cells induced by oxygen-glucose deprivation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To determine whether oxygen-glucose deprivation (OGD) induces C6 cell injury, and whether 5-lipoxygenase (5-LOX)/cysteinyl leukotriene (CysLT) pathway is involved in OGD-induced injury.</p><p><b>METHODS</b>After OGD treatment and recovery for various durations, the viability of C6 cells was determined, and the effects of 5-LOX inhibitors and CysLT receptor antagonists were investigated. Intracellular distribution of 5-LOX protein was detected by immunocytochemistry, and the mRNA expressions of CysLT1 and CysLT2 receptors were detected by RT-PCR. The effect of leukotriene D(4) (LTD(4)) on C6 cells was also investigated.</p><p><b>RESULT</b>OGD for 4-8 h followed by recovery for 24-72 h significantly induced C6 cell injury. Neither 5-LOX inhibitors nor CysLT receptor antagonists inhibited OGD-induced injury. OGD did not induce 5-LOX translocation into the nuclear membrane. C6 cells highly expressed CysLT(2) receptor, but the expression of CysLT1receptor was much weaker; the expression was not affected by OGD. In addition, LTD(4) did not affect C6 cells significantly.</p><p><b>CONCLUSION</b>OGD can induce C6 cell injury, but 5-LOX/CysLT pathway might be not involved in OGD-induced injury.</p>

Clinical practice and evaluation of relative fluid resuscitation formula at burn shock stage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To evaluate the application of the Third Military Medical University (TMMU) formula for fluid resuscitation on the major burn patients during shock stage.</p><p><b>METHODS</b>Seventy-one thermal injury patients (burn area more than 30% TBSA, without especial illness, hospitalization within 8 hour after burn) admitted from 2005 to 2007 were divided into adult group (n = 46), child group (n = 25). Fluid resuscitation was initiated as per the TMMU formula.</p><p><b>RESULTS</b>All patients survived the first 48 hours post burn injury and none developed recognized complications associated with fluid resuscitation. The average infused fluid was 16% approximately 38% more than the calculated in both adult and child groups. The average urine output during the first 24 hours post burn injury was 1.1 approximately 1.2 mL x kg(-1) x h(-1) in the two groups, but reached 1.2 mL and 1.7 mL x kg(-1) x h(-1) during the second 24 hours in adult and child groups respectively.</p><p><b>CONCLUSION</b>TMMU formula for fluid resuscitation is a feasible option for major burn patients. Individual fluid resuscitation, guided by the physiological response, is also important and necessary.</p>

Research advance in cysteinyl leukotriene receptors with brain injury / 浙江大学学报·医学版

Based on the findings recently reported, cysteinyl leukotriene receptors, both CysLT (1) and CysLT(2) receptors, are involved in the ischemic and traumatic brain injury in vivo. CysLT(1)receptor regulates the increased permeability of blood-brain barrier and the related vasogenic brain edema, astrocyte proliferation, and inflammatory responses after brain ischemia; while CysLT(2)receptor regulates AQP4 expression and the related cytotoxic brain edema, and astrocyte injury. A new subtype of CysLT receptor, GPR17, is also involved in brain ischemic injury. The roles of CysLT receptors in brain injury or neuroprotection from the injury should be further understood. This understanding is necessary to accelerate the screening and development of the new drugs for the prevention and treatment of brain injury with the receptors as therapeutic targets.

Colophony Adsorbing Isolating Herbicidal Substance from Mycotoxin Produced by Pythium aphanidermatum / 微生物学通报

Four kinds of colophony were used to isolate the herbicidal substance from the toxin produced by isolate PAM1 of Pythium aphanidermatum, which had herbicidal activity to Digtaria sanguinealis L and the results showed X-5 was the best one for absorbing herbicidal substance among the four kinds of colophony used. Four solvents including 50% ethanol, 95% ethanol, ethyl acetate and acetone were used as eluting solvent and 2 procedures were tested, and the results of growth inhibition and seed germination indicated that the best eluting procedure was procedure 1.

Short and mid-term effects of percutaneous transcatheter closure of ventricular septal defects on the cardiac remodeling / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the short and mid-term changes of the cardiac morphology after percutaneous transcatheter closure of ventricular septal defects (VSD) with transthoracic echocardiography (TTE).@*METHODS@#The left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), left atrial diameter (LAd), and right ventricular diameter (RVd) in 30 VSD patients were measured before the VSD closure,and on the 3rd day, 3rd month, and 6th month after the VSD closure by TTE.@*RESULTS@#LVEDD and LVEDV significantly decreased on the 3rd day after the VSD closure compared with pre-VSD closure. LVEDD and LVEDV continuously decreased on the 3rd month and 6th month after the VSD closure. LAd was smaller on the 3rd month and 6th month after the VSD closure, but there was not significant difference between the 3rd and 6th month. RVd increased on the 3rd day after the VSD closure, while no significant difference was found among the 3rd month and 6th month before and after VSD closure.@*CONCLUSION@#Percutaneous transcatheter VSD closure may effectively improve the cardiac remodeling in VSD patients in the short and mid-term follow-up.

H2 receptor mediates the protective effect of histamine against the cellular edema and viability reduction induced by oxygen-glucose deprivation in rat hippocampal slices / 药学学报

<p><b>AIM</b>To determine the effect of histamine on ischemia-induced cellular edema and viability reduction in rat hippocampal slices, and the involved subtypes of histamine receptor in this effect.</p><p><b>METHODS</b>In vitro ischemic injury of hippocampal slices was induced by oxygen-glucose deprivation (OGD). The slice injury was determined by real-timely measuring the changes of light transmittance (LT) for the cellular edema in CA1 region of the hippocampal slice, and by detecting the product of 2, 3, 5-triphenyltetrazolium chloride (TTC), formazan, for the slice viability. The effect of histamine at various concentrations on the slice injury was observed, and the blockage by antagonists of histamine receptors was also investigated.</p><p><b>RESULTS</b>Histamine (0.01-10 micromol x L(-1)) inhibited the peak value of LT during OGD in hippocampal slices and improved the reduced viability after OGD. Diphenhydramine (0.1-10 micromol x L(-1)), an H1 receptor antagonist, did not affect the effect of histamine, while cimetidine (0.1-10 micromol x L(-1)), an H2 receptor antagonist, partly abolished the protective effect of histamine.</p><p><b>CONCLUSION</b>Histamine protects hippocampal slices against ischemia-induced cellular edema and viability reduction; this effect might be mediated via, at least partly, H2 receptor.</p>