番泻苷A对2型糖尿病小鼠动脉粥样硬化斑块形成及5-羟色胺信号分子表达的影响

目的·研究番泻苷A (sennoside A,SA)对2型糖尿病(diabetes mellitus type 2,T2DM)小鼠动脉粥样硬化斑块形成和5-羟色胺(5-hydroxytryptamine,5-HT)及其受体表达的影响。方法·将载脂蛋白E基因敲除小鼠12只随机分为模型组(model组)和治疗组(model+SA组),每组6只,同遗传背景C57BL/6J小鼠6只作为对照组(control组)。Control组普通饲养,model组和model+SA组在高脂饲养基础上每日给予腹腔注射30 mg/kg链脲佐菌素(streptozotocin,STZ)建立T2DM模型。Model+SA组每日给予SA (45 mg/kg)灌胃干预8周,control组和model组给予等体积双蒸水灌胃。比较造模及治疗前后小鼠体质量、空腹血糖和餐后2 h血糖情况,采用油红O染色和苏木精-伊红染色(hematoxylin-eosin staining,H-E染色)观察小鼠主动脉斑块面积,并用ELISA试剂盒测定小鼠血清和胸主动脉中5-HT水平,采用蛋白质印迹法(Western blotting)检测小鼠胸主动脉中5-羟色胺2B受体(5-hydroxytryptamine receptor 2B,HTR2B)和5-羟色胺转运蛋白(serotonin transporter,SERT)的表达情况。结果·与control组相比,model组小鼠体质量、空腹血糖和餐后2 h血糖均升高,糖代谢紊乱;主动脉斑块形成,胸主动脉中HTR2B、SERT蛋白表达升高;胸主动脉5-HT浓度降低,血清5-HT浓度升高(均P<0.05)。给予SA治疗后,与model组相比,model+SA组小鼠体质量下降,空腹血糖和餐后2 h血糖水平明显改善;主动脉斑块面积减少,胸主动脉HTR2B、SERT蛋白表达显著降低;胸主动脉5-HT浓度升高,血清5-HT浓度降低(均P<0.05)。结论·SA可减少T2DM小鼠动脉粥样硬化斑块面积,其作用可能与降低血糖、抑制5-HT及其受体表达有关。

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor activity.Methods:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control group.Group 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),respectively.All treatments lasted for 21 days.Samples were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay.The amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies.Results:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and testes.NAC or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and testes.The combination of both treatments appeared to be more effective.The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to androgen.However,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to DEHP.Conclusions:The possibility that NAC and ZnSO_(4) could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

大疱性类天疱疮患者疱液中HBD-2、CXCR5及ECP的表达水平及意义

目的:探究大疱性类天疱疮(BP)患者疱液中人类β防御素2(HBD-2)、趋化因子受体5(CXCR5)、嗜酸性粒细胞阳离子蛋白(ECP)的表达水平及意义。方法:选取80例BP患者为BP组;50例非BP患者为非BP组,根据BP活动性皮损面积(A)和活动性皮损数目(B)将BP组分为重度组、中度组及轻度组;随访6个月,根据疾病复发及并发症发生情况将BP组患者分为预后不良组及预后较好组,采用ELISA法检测BP患者及非BP患者、不同病情程度BP患者及不同预后结果BP患者之间HBD-2、CXCR5、ECP水平差异,并分析HBD-2、CXCR5、ECP水平与BP严重程度及患者预后的相关性。结果:BP组HBD-2、CXCR5、ECP水平均高于非BP组(P<0.05)。不同病情程度BP患者疱液HBD-2、CXCR5、ECP水平比较:重度组>中度组>轻度组(P<0.05)。相关性分析显示,BP患者疱液HBD-2、CXCR5、ECP水平与病情严重程度均呈正相关关系(P<0.05)。疱液HBD-2、CXCR5、ECP水平联合检测评估BP严重程度的曲线下面积(AUC)大于各指标单独检测(P<0.05)。预后不良组HBD-2、CXCR5、ECP水平均高于预后较好组(P<0.05)。疱液HBD-2、CXCR5、ECP水平联合检测预测BP患者预后的AUC大于各指标单独检测(P<0.05)。结论:大疱性类天疱疮患者疱液中HBD-2、CXCR5、ECP水平异常升高与疾病严重程度相关,且各指标联合检测对BP严重程度及患者预后具有预测价值。

清渣汤对玫瑰痤疮模型小鼠皮损组织VEGF、TLR2、KLK5表达的影响

目的:观察清渣汤口服对玫瑰痤疮模型小鼠皮损组织血管内皮生长因子(VEGF)、Toll样受体2(TLR2)、激肽释放酶5(KLK5)表达的影响。方法:7周龄健康雄性小鼠36只,用随机数字表法将其分为6组:清渣汤高剂组、中剂组、低剂组、阳性对照组(多西环素片)、模型对照组、正常对照组,每组6只。除正常组外,其余各组均进行玫瑰痤疮造模。造模24 h后给药,模型组给予0.2 mL生理盐水灌胃,清渣汤3剂组分别给予25 mg/kg(低剂量组)、50 mg/kg(中剂量组)和100 mg/kg(高剂量组)清渣汤灌胃,阳性对照组给予30 mg/kg盐酸多西环素溶液灌胃,每日1次,共给药4周。免疫组化法检测皮损部位皮肤组织VEGF、TLR2、KLK5蛋白表达水平。结果:模型组小鼠皮损组织VEGF、TLR2、KLK5蛋白表达较正常组明显增强(P<0.01);与模型组比较,阳性对照组和清渣汤高、中、低剂量组小鼠皮损组织VEGF、TLR2、KLK5蛋白表达减弱(P<0.05)。结论:清渣汤能够抑制玫瑰痤疮小鼠模型皮损部VEGF、TLR2、KLK5蛋白表达水平,从而减轻炎症反应。

Augmentative effect of tetrandrine on pentobarbital hypnosis mediated by 5-HT_(1A) and 5-HT_(2A/2C) receptors in mice

It has been reported that augmentative effect of tetrandrine on pentobarbital hypnosis in mice may be related to serotonergic system. The present study was undertaken to investigate the interaction of tetrandrine and different 5-HT receptors on pentobarbital-induced sleep by using the loss-of-righting reflex method. The results showed that augmentative effect of tetrandrine on pentobarbital hypnosis in mice were potentiated by the p-MPPI （5-HT1A receptor antagonist） （1 mg/kg, i.p.） and ketanserin （5-HT2A/2C receptor antagonist） （1.5 mg/kg, i.p.）, respectively. Pretreatment with either 8-OH-DPAT （5-HT1A receptor agonist） （0.1 mg/kg, s.c.） or DOI （5-HT2A/2C receptor agonist） （0.2 mg/kg, i.p.） significantly decreased pentobarbital-induced sleep time, and tetrandrine （60 mg/kg, i.g.） significantly reversed this effect. These results suggest that both the 5-HTLA and 5-HT2A/2C subfamily may be involved in the potentiating mechanism of tetrandrine＇s effects on pantobarbital hypnosis.

Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease

Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese:a Case-control Study

Objective To investigate the association between low-density lipoprotein receptor-related protein 5 （LRPS） variants （rs12363572 and rs4930588） and type 2 diabetes mellitus （T2DM） in Han Chinese. Methods A total of 1842 T2DM cases （507 newly diagnosed cases and 1335 previously diagnosed cases） and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms （SNPs）. Odds ratios （ORs） and 95% confidence intervals （95% CIs） were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index （BMI）, the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype ~ was associated with reduced risk of T2DM （OR 0.820, 95% CI 0.732-0.919）. In addition, rs12363572 was associated with BMI （P〈0.001） and rs4930588 was associated with triglyceride levels （P=0.043） in 507 newly diagnosed T2DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM.

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.

Roles of 5-HT2 receptors in effects of DOM,ketamine and methamphetamine on prepulse inhibition in Sprague Dawley rats

OBJECTIVE Prepulse inhibition(PPI)of the acoustic startle response provides a measure of sensorimotor gating system mecha⁃nisms,which is known to be impaired in schizo⁃phrenia patients.We assessed the effects of the 5-HT2A/2C receptor agonist(±)2,5-dimethoxy-4-methylamphetamine(DOM),the NMDA receptor antagonist ketamine,the dopamine receptor ago⁃nist methamphetamine(Meth)on PPI and the startle magnitude in SD rats.METHODS AND RESULTS Systemic administration of the three compounds all dose-dependently reduced PPI.However,as far as startle magnitude,only DOM at the doses of 3 mg·kg-1 reduced that,while both ketamine and Meth did not change the startle magnitudes.Furthermore,to determine whether 5-HT2A receptor mediate this effect,the non-spe⁃cific 5-HT2 receptor antagonist cyproheptadine,specific 5-HT2A receptor antagonist ketanserin and specific 5-HT2C receptor antagonist SB242084 were tested.Cyproheptadine,ketan⁃serin and SB242084 did not alter startle ampli⁃tude by themselves in SD rats and only ketanserin slightly increased PPI at higher dose(3 mg·kg-1).PPI impairment induced by DOM was restored by pretreatment of cyproheptadine(1 mg·kg-1)and ketanserin(1 mg·kg-1),while not by pretreat⁃ment of SB242084(1 mg·kg-1).Damage of PPI induced by ketamine and Meth was not reversed by cyproheptadine(1 and 5 mg·kg-1).CONCLU⁃SION The receptor mechanisms underlying the disruption of PPI caused by DOM,ketamine and Meth were different from each other,at least 5-HT2A receptor was not the junction receptor for which the three chemicals acted.

ENHANCEMENT OF DNA SYNTHESIS IN CULTURED ADULT RAT HEPATOCYTES BY 5-HT THROUGH STIMULATION OF 5-HT_2RECEPTOR

Hepatocytes were isolated from livers of adult male SpragueDawley rats and cultured in Williams'E Medium with 3 H thymidine. The effect of 5hydroxytryptamine (5HT) was investigated through adding various concentrations (10-810-3 mol/L) of 5HT to the hepatocyte cultures in the presence or absence of epidermal growth factor (EGF) and insulin. The involvement of 5HT2 receptor was examined by adding a 5HT2 receptor antagonist, ketanserin (10-6 mol/L), to some of the cultures containing 5HT. The increment of DNA synthesis was measured by 3 H thymidine incorporation. The results showed that 5HT2 (10-6 mol/L) significantly (P<005) increased the amount of DNA synthesis induced by EGF and insulin in the cultured adult rat hepaptocytes. The effect of 5HT in enhancing DNA synthesis began to appear at a concentration between 10-7 and 10-6 mol/L and reached maximum at concentrations of 10-4 mol/L. The enhancement of DNA synthesis by 5HT was significantly (P<005) antagonized by ketanserin, suggesting that this effect of 5HT was mediated by 5HT2 receptor subtype.

Effects of Estradiol on 5-HTsA and 5-HT2c Receptor Immunolabeling in Rat Hippocampus

Steroid hormones participate in the modulation of serotonergic transmission, including the regulation of synthetic and metabolic enzyme production, as well as receptor and transporter activity. The changes of 5-HT5A and 5-HT2c immunolabeling induced by steroids in the hippocampus ofovariectomized rats were studied in this work. Densitometric analysis in rat hippocampi were carried out for adjacent brain coronal immunolabeled sections after treatment with subcutaneous injections of vehicle, estradiol, progesterone or the combination of both steroids in ovariectomized rats. Exposure to estradiol and the combination of estradiol and progesterone significantly reduced the 5-HT5A-like immunosignal in the CA 1 region while progesterone did not induce changes. On the other hand, exposure to the combination of estradiol and progesterone or estradiol alone increased the 5-HT2c immunosignal in the same region. These results indicate that estradiol is involved in the discrete regulation of serotonin receptors 5-HT5A and 5-HT2c in rat hippocampus.

Role of 5-HT2A Receptors in Immunomodulation in Animal Models of Aggressive Behavior

Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.

血清TGR5 mRNA和BNIP3 mRNA在急性心肌梗死患者中的表达水平及临床意义

目的 探究血清G蛋白偶联胆汁酸受体5(TGR5)mRNA与Bcl-2/腺病毒QE1B-19kDa相互作用蛋白3(BNIP3)mRNA在急性心肌梗死(AMI)患者中的表达水平情况,以及二者对于术后心脏不良事件(MACE)发生的预测价值。方法 选取首都医科大学门头沟教学医院2018年1月至2020年1月收治的98例进行经皮冠状动脉介入术(PCI)的AMI患者[AMI患者包括急性非ST段抬高型心肌梗死(NSTEMI)46例与急性ST段抬高型心肌梗死(STEMI)52例]为研究组,另选取同期90例体检健康者作为对照组。采用实时荧光定量PCR(qRT-PCR)检测血清TGR5 mRNA和BNIP3 mRNA表达水平,根据PCI术后随访结果将研究组分为MACE组(46例)和非MACE组(52例)。收集两组患者临床资料,采用Pearson法分析术后MACE组血清TGR5 mRNA与BNIP3 mRNA表达水平的相关性,采用受试者工作特征(ROC)曲线分析血清TGR5 mRNA和BNIP3 mRNA对于术后AMI患者MACE发生的预测价值,采用Logistic回归分析AMI患者术后MACE发生的影响因素。结果 研究组血清TGR5 mRNA表达水平显著低于对照组,血清BNIP3 mRNA表达水平显著高于对照组,差异有统计学意义(P<0.05);术后MACE组左心室射血分数(LVEF)、TGR5 mRNA表达水平显著低于非MACE组,血清肌酐(SCr)、红细胞分布宽度(RDW)、Killip分级Ⅲ+Ⅳ级比例、BNIP3 mRNA表达水平显著高于非MACE组,差异有统计学意(P<0.05);经Pearson相关性分析,血清TGR5 mRNA与BNIP3 mRNA表达水平呈负相关(r=-0.543,P<0.05);ROC曲线分析显示,血清TGR5 mRNA预测AMI患者MACE发生的曲线下面积(AUC)为0.704(95%CI:0.601~0.808),血清BNIP3 mRNA预测AMI患者MACE发生的AUC为0.762(95%CI:0.696~0.883),血清TGR5 mRNA与BNIP3 mRNA联合预测AMI患者术后MACE发生的AUC为0.867(95%CI:0.783~0.932),优于二者单独预测(Z_(二者联合-TGR5)=2.346,Z二者联合-BNIP3=1.715,P=0.019、0.043);Logistic回归分析结果显示,TGR5 mRNA、BNIP3 mRNA、RDW是AMI患者术后MACE发生的影响因素(P<0.05)。结论 TGR5 mRNA在AMI患者血清中呈低表达水平,BNIP3 mRNA在AMI患者血清中呈高表达表达,二者对于预测术后MACE发生具有重要意义。

糖尿病大鼠胃肠功能紊乱时β_2-肾上腺素能受体与5-羟色胺受体表达的变化

目的 探讨糖尿病胃肠功能紊乱大鼠胃肠道自主神经病变的靶位。 方法 应用四氧嘧啶 糖尿病大鼠模型 ,对其胃肠道多个部位的 β2 肾上腺素能受体 (β2 AR)与 5 羟色胺受体 (5 HTR)的数量进行免疫组化检测。 结果 糖尿病大鼠胃窦与结肠的 5 HTR显著增多 ;糖尿病大鼠黏膜内分泌细胞的 β2 AR在肠道均有减少。 结论 胃肠道的 β2 AR与 5 HTR的数量在糖尿病胃肠功能紊乱时发生了改变 ,这种改变很可能是糖尿病胃肠功能紊乱的发病基础。

中国傣族、景颇族人群中与艾滋病相关的CCR5△32、CCR2b-64I、SDF1-3′A等位基因多态性分布

为了调查HIV 1感染相关的等位基因CCR5△32、CCR2b 64I、SDF1 3′A在我国云南省德宏州傣族景颇族人群中的频率和多态性分布,此课题以101例傣族和113例景颇族人群为研究对象,应用PCR、PCR RFLP(聚合酶链反应 限制性片段长度多态性)分析方法进行检测,计算突变基因频率;并对其群体分布、性别分布进行统计学分析。结果表明,中国傣族景颇族人群中未发现CCR5△32等位基因突变;傣族CCR2b 64I、SDF1 3′A基因突变频率分别为0.2130和0.2030,景颇族CCR2b 64I和SDF1 3′A基因突变频率分别为0.1637和0.1770;与中国汉族人群相比较,傣族和景颇族中SDF1 3′A突变频率较低(P值分别为0.0322和0.0021);两个民族的CCR2b 64I和SDF1 3′A等位基因群体分布符合Hardy Weinberg平衡,在性别之间分布无显著差异。中国傣族景颇族人群的CCR2b 64I等位基因的突变频率与汉族人相似,SDF1 3′A等位基因的突变频率比汉族人低,此两种突变基因在艾滋病发病过程中的影响值得进一步研究。由于未发现CCR5△32基因突变,中国傣族景颇族人群对HIV 1感染可能有较大的遗传易感性。

5-羟色胺2A受体基因多态性与利培酮治疗中国首发精神分裂症患者疗效关联(英文)

背景 5-羟色胺2A受体基因已经证实为精神分裂症的候选易感基因，因为阐明其作为非典型抗精神病药物重要作用靶点减轻阴性症状已引起业界倍加关注。本研究试图探讨：（1）5-HT2A受体基因T102C多态性在不同临床亚型之间等位基因和基因型频率的关系，（2）5-H12A受体基因T102C在利培酮高剂量组和低剂量组之间基因型和等位基因分布频率的关系，（3）5-H12A受体基因T102C多态性在治疗有效组与无效组之间的基因型和等位基因分布频率的关系，（4）5-羟色胺2A受体T102C基因多态性是否与中国首发精神分裂症患者利培酮疗效有关。方法 对201例精神分裂症初发期患者分别进行利培酮治疗[3～5mg／d，平均（3．2±1．3）mg／d]，疗程8周。采用聚合酶链式反应扩增与限制性片段长度多态性（PCR-RFLP）技术检测5-H12A受体基因T102C多态性。以临床亚型将精神分裂症患者划分为偏执型、瓦解型、未定型和其他型，分析不同临床亚型等位基因和基因型频率的差异；按服用利培酮剂量划分低剂量组（〈4mg／d）和高剂量组（≥4mg／d），经比较利培酮高剂量组和低剂量组的5-H12A受体基因T102C基因型和等位基因分布频率差异性；同时以阴性和阳性症状量表（PANSS）总减分率〉50％有效，≤50％为无效以分析治疗有效组与无效组之间的基因型和等位基因分布频率差异有无显著性；以PANSS评定患者治疗前及治疗后2周、4周、6周和第8周末的精神症状，比较5-H12A受体T102C各基因亚型与年龄、发病年龄、PANSS总分值、阳性症状基线分、阴性症状基线分、一般病理症状基线分、PANSS总减分率、阳性症状减分率、阴性症状减分率和一般病理症状减分率的差异。结果 5-H他A受体T102C基因型在患者组分布频率均符合H-W平衡定律（P〉0．05）；不同临床诊断亚型精神分裂症患者等位基因和基因型频率无显著性差异（χ^2=0．415，P=0．937；χ^2=1．705，P=0．941）；高剂量组与低剂量组之间的基因型和等位基因分布频率差异均无显著性（χ^2=2．402，P=0．301；χ^2=2．465，P=0．116）；治疗有效和无效组的基因型和等位基因分布频率的差异无显著性（χ^2=1．995，P=0．369；χ^2=1．939，P=0．164）；各基因型亚组的年龄、发病年龄及其病程差异均无显著性（P均大于0．05）；但基因亚组A1／A1的治疗前PANSS总分（χ^2=4．076，P=0．018）和阴性症状分（χ^2=3．946，P=0．021）以及治疗结束PANSS总分减分率（χ^2=4．036，P=0．019）和阴性症状减分率（χ^2=3．876，P=0．022）均显著高于A1／A1及A1／A1基因型。结论 （1）首发精神分裂症患者不同临床亚型5-H12A受体基因T102C基因型和等位基因频率无显著差异。（2）利培酮高剂量组和低剂量组5-H12A受体基因T102C基因型和等位基因分布频率没有显著性差异。（3）治疗有效组与无效组之间5-H12A受体基因T102C基因型和等位基因分布频率也无显著性差异。（4）5-H12A受体T102C A1／A1基因亚型可能影响中国首发精神分裂症患者对利培酮的治疗效应。

5-HTR4和GABRG2基因多态性与精神分裂症关系

目的探讨5-羟色胺4受体基因(5-HTR4)和γ-氨基丁酸-γ2受体基因(GABRG2)基因多态性与精神分裂症的关系。方法在95个中国北方汉族精神分裂症患者和他们的健康父母组成的核心家系中,以聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对5-HTR4基因rs888957(C/T碱基改变)和GABRG2基因rs211014(T/G碱基改变)单核苷酸多态性(SNP)进行检测。应用基于家系的连锁不平衡方法分析基因型数据。结果(1)5-HTR4基因rs888957及GABRG2基因rs211014基因型频率的分布均符合Hardy-Weinberg平衡;(2)传递不平衡检验(TDT)结果提示,5-HTR4基因rs888957及GABRG2基因rs211014与精神分裂症无连锁及关联;(3)UNPHASED双位点单体型分析结果显示,rs888957-rs211014单体型系统与精神分裂症无关联(P>0.05);(4)5-HTR4基因的rs888957位点等位基因分布与精神分裂症的阳性症状钟情妄想相关联(P<0.01)。GABRG2基因的rs211014位点等位基因分布与精神分裂的阳性症状冲动伤人行为相关联(P<0.05)。结论5-HTR4基因rs888957位点及GABRG2基因rs211014位多点态性可能与精神分裂症无关,但不能排除5-HTR4基因及GABRG2基因其他SNPs与精神分裂症相关联。

曲妥珠单抗联合奥沙利铂、5-氟尿嘧啶治疗HER-2/neu高表达晚期胃癌的临床疗效观察

目的观察曲妥珠单抗联合奥沙利铂、5-氟尿嘧啶治疗HER-2/neu高表达晚期胃癌的临床疗效与安全性。方法选择2009年10月—2011年4月收治的晚期胃癌患者84例为研究对象,随机分为观察组(44例)与对照组(40例),对照组给予奥沙利铂联合5-氟尿嘧啶化疗方案,观察组在此基础上加用曲妥珠单抗,2组均化疗4个周期,并进行24个月随访观察,对比2组化疗结束后临床疗效、化疗期间药物毒性反应及24个月内存活情况。结果(1)2组化疗结束后1个月,观察组总体有效率为63.6%,KPS评分为(79.6±6.4)分,均高于对照组的42.5%和(75.8±5.7)分,HER-2细胞外定量(28.4±6.6)μg/L低于对照组的(31.5±7.2)μg/L,差异均有统计学意义(P<0.05)。(2)观察组心脏毒性、发热或寒战、皮疹发生率显著高于对照组(分别为15.9%vs 2.5%、25.0%vs 10.0%、29.5%vs 7.5%),差异均有统计学意义(P<0.05)。(3)观察组化疗结束后24个月平均生存率为(43.5±7.1)%,平均存活时间为(16.9±3.1)个月,均高于对照组的(39.7±5.8)%和(14.6±2.8)个月,差异有统计学意义(P<0.05)。结论对HER-2/neu高表达晚期胃癌患者在行奥沙利铂联合5-氟尿嘧啶化疗基础上使用曲妥珠单抗,能明显提高临床疗效,延长患者存活时间;同时需密切监测曲妥珠单抗的药物毒性尤其是心脏毒性。

TLR-2和TLR-5在弥漫大B细胞淋巴瘤组织中的表达及临床意义

目的探讨Toll样受体-2(TLR-2)和Toll样受体-5(TLR-5)在弥漫大B细胞淋巴瘤(DLBCL)组织中的表达及其临床意义。方法采用免疫组化法检测60例DLBCL组织标本中TLR-2和TLR-5的表达,以21例反应性淋巴结增生组织为对照组,并分析TLR-2和TLR-5表达与DLBCL临床病理特征的关系。结果 TLR-2在DLBCL组织中的阳性表达率为78.3%,在对照组中为28.5%,差异有统计学意义(P<0.05);TLR-2表达与年龄、性别和ECOG评分无关,与临床分期、乳酸脱氢酶水平、B症状、IPI、免疫亚型以及结外受累有关。TLR-5在DLBCL中的阳性表达率为26.6%,在对照组中为23.8%(P>0.05);TLR-5表达与各临床病理特征无关。结论 TLR-5与DLBCL临床特征无关;TLR-2可能参与了DLBCL的发生和发展,有望作为判断其预后的生物学指标。