Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Bradykinin B_(2）受体在大鼠脑胶质瘤模型上的定位

目的 研究 Bradykinin选择性地开通恶性脑肿瘤血脑屏障的机理。方法 通过双重免疫组化染色法 ,确定 Bradykinin B2 受体存在的部位。结果 在正常脑组织和肿瘤组织中的毛细血管内皮细胞上不存在 B2 受体 ,肿瘤细胞表达高水平的 B2 受体。结论 我们推测小剂量 Bradykinin灌注能选择地打开肿瘤的血脑屏障而不影响正常血脑屏障通透性的机理在于肿瘤细胞表达高水平的 B2 受体。

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Expression of HER2 and bradykinin B_1 receptors in precursor lesions of gallbladder carcinoma

AIM： To determine the expression of HER2 and bradykinin B1 receptors （B1R） in the two pathogenic models of gallbladder cancer： the metaplasia dysplasia carcino ma and the adenoma carcinoma pathways.METHODS： Receptor proteins were visualized by immunohistochemistry on 5-μm sections of paraffin-embedded tissue. Expression of both receptors was studied in biopsy samples from 92 patients （6 males and 86 females; age ranging from 28 to 86 years, mean 56 years）. High HER2 expression in specimens was additionally investigated by fluorescence in situ hybridization. Cell proliferation in each sample was assessed by using the Ki-67 proliferation marker.RESULTS： HER2 receptor protein was absent in adenomas and in normal gallbladder epithelium. On the contrary, there was intense staining for HER2 on the basolateral membrane of epithelial cells of intestinal metaplasia （22/24; 91.7%） and carcinoma in situ （9/10; 90%）, the lesions that displayed a significantly high proliferation index. Protein up-regulation of HER2 in the epithelium with metaplasia or carcinoma in s/tu was not accompanied by HER2 gene amplification. A similar result was observed in invasive carcinomas （0/12）. The B1R distribution pattern mirrored that of HER2 except that B1R was additionally observed in the adenomas. The B1R appeared either as cytoplasmic dots or labeling on the apical cell membrane of the cells composing the epithelia with intestinal metaplasia （24/24; 100%） and carcinoma in situ （10/10; 100%） and in the epithelial cells of adenomas. In contrast, both HER2 （4/12; 33%） and B1R （1/12; 8.3%） showed a low expression in inva- sive gallbladder carcinomas.CONCLUSION： The up-regulation of HER2 and B1R in precursor lesions of gallbladder carcinoma suggests cross-talk between these two receptors that may be of importance in the modulation of cell proliferation in gallbladder carcinogenesis,

Lactotripeptides Inhibiting ACE1 Elevate the Plasma Bradykinin Concentration Acutely in a Placebo-Controlled, Double-Blind, Cross-Over, 4-Week Trial in Healthy Volunteers

This placebo-controlled, double-blind, cross-over intervention with twelve normotensive healthy volunteers tested the effects of milk products containing either 5 or 50 mg of ACE1-inhibitory lactotripeptides (isolecine-proline-proline, Ile-Pro-Pro, and valine-proline-proline, Val-Pro-Pro) and placebo milk drink (with similar taste) on plasma bradykinin levels. The subjects consumed one of the three test products in a random order, double-blinded, and four-week trial. On the first day (day 1) and on the last day (day 29) i.e. after four weeks’ treatment with one of the products, the acute effect with the same single dose was assayed. Other markers of the renin-angiotensin-aldosterone system (RAAS) were measured from plasma four times on the same days when we also assessed daytime urinary excretion of biomarkers of endothelial function. Neither acute nor prolonged administration of the ACE-1 inhibiting peptide drinks significantly lowered blood pressure of the normotensive subjects. The most important finding was the dose-dependent, and linear increase in plasma bradykinin concentrations after acute dosing on the first day;it was nearly statistically significant also on the day 29 (p 0.06). Other indicators of RAAS or endothelial function did not differ from those of placebo after the acute or prolonged treatments. Our results suggest that even weak inhibitors of ACE-1, such as the lactotripeptides Ile-Pro-Pro and Val-Pro-Pro, are able to diminish the breakdown of bradykinin and therefore increase plasma bradykinin levels. This may partly explain the blood pressure lowering and vasodilatory effects of lactotripeptides, shown by us earlier in mildly hypertensive subjects.

Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway

Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

Effects of Bradykinin B_2 Receptor Blockade on Infarct Size and Hemodynamics after Myocardial Infarction in Enalapril-treated Rats

Objectives To study the effects of bradykinin （BK） B2 receptor blockade on infarct size and hemodynamics after myocardial infarction （MI） in rats with angiotensin-converting enzyme （ACE） inhibition therapy. Methods MI was produced by ligating the left coronary artery. The effects of enalapril （ 500 μg/kg·day）, enalapril （ 500 μg/kg · day） with BK B2 receptor antagonist Hoe-140 （500 μg/kg · day）, angiotensin Ⅱ （Ang Ⅱ） type 1 （AT1） receptor antagonist losartan （3 mg/kg · day） on infarct size, left ventricular systolic pressure （ LVSP）, cardiac output index （CI） and stroke volume index （SVI） were observed in rats after MI. Treatments were started on the 2nd day after MI and continued for another 6 weeks. Results Enalapril reduced infarct size and improved CI and SVI compared with the untreated MI group （ P 〈 0. 05 ）, and these effects of enalapril were significantly blunted by concomitant treatment with Hoe-140 （P 〈 0. 05）. Losartan was less effective than enalapril. LVSP were unchanged in the three treatment groups. Conclusions BK can reduce infract size and improve hemodynamics in rats following MI. The cardioprotective effects of ACEI partly result from the action of BK exerted through the B2 receptor.

Down-regulation of Cardiac Bradykinin B2 Receptors and eNOs mRNA in Rats with Remnant Kidneys

The changes in the expression of cardiac bradykinin B2 receptors (BKB2Rs) and endogenous nitrix oxide synthase (eNOs) mRNA were studied in rats with remnant kidneys. Thirty-two rats were divided into sham-operated and experimental groups randomly (n=16 in each group). The remnant kidney model was established by 2-stage 5/6 nephrectomy. Blood pressure and serum Cr were measured before operation and 15, 30, 60, 120 days after 5/6 nephrectomy. Eight animals in each group were killed at the first month and 4th month after the operation. The expression of BKB2Rs and eNOs mRNAs was detected by using RT-real time PCR from isolated left ventricle, and their correlation was also analyzed. The results showed that blood pressure and serum Cr were increased significantly 15 days after 5/6 nephrectomy (both P<0.01), and the hypertension and azomia existed constantly till 120 days but had no significant fluctuation. Cardiac BKB2Rs and eNOs mRNA was declined time-dependently (both P<0.05). And there was a close positive correlation between cardiac BKB2Rs and eNOs mRNA (r=0.82, P<0.01). It was suggested that a significant chronic renal failure can be produced at least 15 days after 5/6 nephrotomy and can sustain more than 4 months. The expression of BKB2Rs and eNOs was down-regulated time-dependently in this model, and there was a significant correlation between them.

Effects of Bradykinin on the Expression of Interleukin-6 in C6 Glioma Cells

OBJECTIVE There is a close correlation between interleukin-6 （IL-6） and malignant proliferation of gliomas. We investigated the effect of bradykinin on the expression of IL-6 in C6 glioma cells. METHODS Semi-quantitive RT-PCR and radioimmunoassay were used to examine the effect of bradykinin on the expression of IL-6 in C6 glioma cells and on the level of IL-6 in the culture medium. RESULTS Using semi-quantitive RT-PCR, the expression of IL-6 mRNA was examined in C6 glioma cells at 0, 5, 10,15, 30, 60 rain following addition of 1μmol/L bradykinin. There was no statistical difference in expression of IL-6 mRNA between the treatment and control groups （P〉0.05） and IL-6 was not detected in the cell culture medium. CONCLUSION Within an hour, IL-6 expression in C6 glioma cells is not induced by bradykinin, suggesting that its clinical application may be useful as a potential therapeutic agent for tumors of the central nervous system .

槲皮素通过下调缓激肽受体B1表达减轻糖尿病大鼠神经病理性疼痛

目的:研究槲皮素通过下调缓激肽受体B1(BDKRB1)表达减轻糖尿病大鼠神经病理性疼痛的机制。方法:60只大鼠腹腔注射60 mg/kg链脲佐菌素建立糖尿病神经病理性疼痛(DNP)大鼠模型,采用随机数表法平均分为5组:模型组、槲皮素(100 mg/kg)组、BDKRB1过表达质粒组、空载质粒组、槲皮素(100 mg/kg)+BDKRB1过表达质粒组,另选12只大鼠腹腔注射等剂量生理盐水作为对照组。各组大鼠以药物分组干预处理后,检测大鼠机械性刺激痛觉、热刺激痛觉与冷刺激痛觉,比较各组机械性缩足阈值、冷刺激抬足时间、热敏潜伏期;免疫组织化学染色检测大鼠脊髓背根神经节淋巴细胞浸润情况,比较各组淋巴细胞功能相关抗原-1(LFA-1)阳性细胞比例;试剂盒测量大鼠血清炎症介质IL-17、环氧化酶-2(COX-2)、IL-18水平;RT-qPCR、Western blot分别检测大鼠脊髓背根神经节BDKRB1 mRNA及蛋白表达水平。结果:与对照组比较,模型组大鼠机械性缩足阈值、热敏潜伏期显著降低(P<0.05),冷刺激抬足时间、LFA-1阳性细胞比例、血清IL-17、COX-2及IL-18水平、BDKRB1mRNA及蛋白表达水平显著升高(P<0.05);与模型组、槲皮素+BDKRB1过表达质粒组分别比较,槲皮素组大鼠机械性缩足阈值、热敏潜伏期均升高(P<0.05),冷刺激抬足时间、LFA-1阳性细胞比例、血清IL-17、COX-2及IL-18水平、BDKRB1 mRNA及蛋白表达水平均降低(P<0.05);BDKRB1过表达质粒组大鼠机械性缩足阈值、热敏潜伏期均降低(P<0.05),冷刺激抬足时间、LFA-1阳性细胞比例、血清IL-17、COX-2及IL-18水平、BDKRB1 mRNA及蛋白表达水平均升高(P<0.05);空载质粒组大鼠各指标均无显著变化(P>0.05)。结论:槲皮素通过下调BDKRB1表达抑制炎症,减少淋巴细胞浸润,减轻糖尿病大鼠神经病理性疼痛症状。

Expression of bradykinin as a substrate of CD26 /DPP IV in rats ischemia/reperfusion injury following lung transplantation

Objective To investigate the expression of bradykinin as a substrate of CD26 /DPP IV in rats with ischemia/reperfusion injury following lung transplantation ( LTx) . Methods Thirty - six syngeneic male SD rats were randomly allocated into control group and experimental group ( n = 18 each) ,and 36 rats served as do-

儿童膀胱过度活动综合征与过敏的相关性分析

目的评价儿童膀胱过度活动综合征(OAB)与过敏的相关性。方法回顾性分析2020年1月至2022年1月于中国医科大学附属盛京医院小儿肾脏风湿科门诊诊断为OAB的663例儿童患者的临床特点,采用logistic回归分析儿童OAB的危险因素,评价抗组胺药物治疗儿童OAB的效果。收集部分OAB患儿血液及尿液标本,分析其中缓激肽和P物质水平。结果湿疹史、荨麻疹史、皮肤瘙痒史、蚊虫叮咬史、过敏性鼻炎史、过敏性咳嗽(含哮喘)史、食物过敏史、便秘史、血总IgE水平是儿童OAB的危险因素(P<0.05)。抗组胺药物治疗儿童OAB的有效率为95.5%,未发生不良反应,提示抗组胺治疗对儿童OAB的疗效及安全性良好,抗组胺治疗无效组OAB儿童合并荨麻疹的比例更高(P<0.05)。抗组胺治疗有效组OAB患儿血总Ig E水平高于无效组(P<0.05)。此外,OAB患儿尿液中缓激肽水平较正常儿童明显升高(P<0.05),P物质水平未见明显升高(P>0.05)。结论儿童OAB与过敏状态有关,既往呼吸道、消化道和皮肤过敏以及血总Ig E水平升高是儿童OAB的危险因素。抗组胺药物治疗儿童OAB安全有效。尿液中缓激肽与儿童OAB发病相关。

尖吻蝮蛇毒腺的缓激肽2型受体结合多肽的筛选与验证

蛇毒已被证明具有抗炎活性,其中包含许多免疫原性弱、活性强的短肽小分子。蛇毒腺是分泌毒液的器官,含有毒素成分及调控其分泌过程的大量生物活性成分。缓激肽2型受体(B2R)参与重要的细胞内信号通路,作为炎症的调节因子成为潜在的抗炎药物开发的靶点。为了获得特异性的B2R结合肽,利用尖吻蝮蛇Deinagkistro-don acutus毒腺T7噬菌体文库对靶点B2R进行3轮生物淘选,测序获得了多个具有潜在结合能力的序列。通过序列长度、溶解性预测、稳定性预测和分子对接等一系列生物信息学分析,最终确定1个含25个氨基酸的肽段,命名为DAvp-4。合成该肽段,通过表面等离子体共振技术验证了DAvp-4和B2R的结合能力,在脂多糖诱导的巨噬细胞模型及糖尿病视网膜病变小鼠模型中肯定了其抗炎作用。此研究不但获得了一个具有成药潜力的毒腺多肽,还显示了噬菌体展示技术在筛选天然产物成分研究中的有效性。

脑缺血与炎症反应

动物实验及临床研究均支持炎症反应参与缺血性脑损伤的理论,但炎症反应本身及其对缺血性脑损害的影响相当复杂。脑缺血后,在缺血损伤区有多种细胞因子表达及炎细胞浸润,构成了缺血性损伤向炎症性损伤转变的基础,最近研究较多的主要有白细胞、肥大细胞、白介素-1β(IL-1β)及肿瘤坏死因子(TNF)等。

缓激肽受体抑制剂对脑缺血再灌注大鼠的脑保护作用

为了探讨缓激肽及其受体在脑缺血急性期对血脑屏障通透性及炎症因子分泌的影响,本研究采用线栓法制作大鼠大脑中动脉梗塞(MCAO)模型,分别应用缓激肽B1和B2受体的特异性抑制剂,在缺血再灌流后24h进行动物行为学评分,TTC染色计算梗死体积,伊文斯蓝染色检测血脑屏障通透性,透射电镜观测血脑屏障超微结构的变化,ELISA对缺血区IL-1β、TNF-α、PGE2进行测定。结果显示:缓激肽B1和B2受体抑制剂能够改善脑缺血大鼠急性期行为学评分、缩小梗死体积、降低血脑屏障通透性、维持血脑屏障结构完整、抑制炎症因子分泌,缓激肽B2受体抑制剂的上述效果优于B1受体抑制剂。以上结果提示缓激肽在脑缺血急性期可以加重脑损伤,其受体的特异性抑制剂可以减轻脑损伤。

激肽释放酶-激肽系统的心血管领域研究进展

本文主要就激肽释放酶 激肽系统 (KKS)在心血管领域的研究进展进行综述。KKS是机体重要的调节系统 ,广泛地存在于许多组织和器官中 ,参与多种生理和病生理过程 ,如心血管、肾脏和神经系统的功能调节 ,平滑肌收缩、葡萄糖代谢、细胞增殖、炎症与疼痛及休克过程等。近年来特别是在心血管方面的研究进展很快 ,许多临床研究和基础实验已证实KKS具有强大的心血管保护作用 ,如调节血压、抑制心肌肥厚的形成、减少缺血再灌注损伤和参与缺血预适应形成。对于其各组分及相应受体作用的研究已达分子水平。基因敲除和转基因模型的建立 ,进一步扩大了研究的深度和广度 。

特异性磷酸二酯酶抑制剂sildenafil增加缓激肽对血-肿瘤屏障的通透性

目的 研究新的cGMP特异性磷酸二酯酶sildenfil抑制剂是否能增加颈动脉灌注缓激肽对脑肿瘤的血-肿瘤屏障的通透性。方法 用放射自显影方法检测单独应用sildenfil,缓激肽以及sildenfil与缓激肽伍用时血-肿瘤屏障通透性的变化。结果sildenfil与缓激肽伍用与单独应用缓激肽相比较,能显著增加反映血-肿瘤屏障通透性的指标单向转运系数Ki值(P<O.O5)。经缓激肽灌流的肿瘤组织中cGMP含量显著增加(P<O.05)。结论特异性磷酸二酯酶抑制剂sildenafil与缓激肽伍用能显著增加血一肿瘤屏障的通透性,从而能够增加药物选择性地转运到脑肿瘤组织。cGMP可能是缓激肽选择性增加血-肿瘤屏障的重要因素之一。

补肾益智汤联合卡巴拉汀治疗阿尔兹海默症临床效果及对血清缓激肽水平的影响

目的：观察补肾益智汤联合卡巴拉汀治疗阿尔兹海默症的临床效果及对血清缓激肽水平的影响。方法：选择医院收治的70例符合入组标准的阿尔兹海默症患者作为研究对象,按随机数字表分为研究组（35例）和对照组（35例）,对照组患者给予卡巴拉汀治疗,研究组在对照组的基础上再口服补肾益智汤,4周为1个疗程,两组均治疗6个疗程,治疗前后进行中医症候积分、简易智能状态量表（mini-mantal state examination,MMSE）评分、修订韦氏记忆量表（WMS）、痴呆量表（Blessed-Roth）评分、阿尔兹海默症评定量表（ADAS-Cog）评分、日常生活能力量表（ADL）评分评判,取清晨空腹血,采用生物素双抗体夹心酶联免疫吸附法进行血清缓激肽（BK）检测,评价中医临床疗效,记录不良反应发生情况。结果：研究组治疗后记忆力减退、腰膝酸软、倦怠嗜卧、表情呆钝、善惊易恐、脑转耳鸣、面颊潮红等中医症候积分均较治疗前明显下降（P〈0.05）,而对照组仅记忆力减退明显改善（P〈0.05）。研究组和对照组治疗后MMSE、WMS明显升高（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显降低（P〈0.05）,且研究组治疗后MMSE、WMS明显高于对照组（P〈0.05）,ADL、Blessed-Roth、ADAS-Cog明显低于对照组（P〈0.05）。研究组和对照组治疗后BK均明显降低（P〈0.05）,研究组治疗后BK明显低于对照组（P〈0.05）。研究组的中医临床疗效总有效率为82.86%,明显高于对照组62.86%,差异具有统计学意义（P〈0.05）。结论：阿尔兹海默症在卡巴拉汀治疗的基础上再加用补肾益智汤治疗的临床疗效明显,能有效改善患者认知功能、记忆功能、痴呆程度及日常生活能力,可能与其降低血清血清缓激肽水平有关。

缓激肽受体信号转导对心血管疾病的调控机制

缓激肽受体是G蛋白偶联受体家族的重要成员之一,它所介导的信号转导对于维持机体内心血管系统动态平衡和炎症方面发挥了重要的作用。近年来,随着荧光共振能量转移(fluorescence resonance energy transfer,FRET)和生物发光共振能量转移(bioluminescence resonance energy trans-fer,BRET)等技术的相继出现,发现缓激肽受体不仅以单体形式存在,还可能以二聚体甚至是高阶寡聚体的形式参与细胞内的病理生理过程。与单体相比,二聚体(或高阶寡聚体)的信号转导和病理功能都产生了相应变化。本文就缓激肽受体及其二聚体所介导的信号途径、生理病理过程及新的研究技术做一简要综述。

缓激肽对大鼠背根神经节分离神经元ATP激活电流的调制作用

在新鲜分离大鼠背根神经节（DRG）的56个细胞标本上，应用全细胞膜片箝技术进行记录。胞外加缓激肽（BK，10－6～10－4mol/L）引起的DRG细胞膜反应结果如下：（1）71.4％的细胞为内向电流，其电流反应的幅值具有明显的浓度依赖性；（2）12．5％的细胞为外向电流；（3）16.1％的细胞未引起可检测的膜反应。单独给予ATP（10－6～10－3mol/L）在大多数受检细胞（54/56）引起一浓度依赖性内向电流，并有明显的去敏感现象。预加BK30S后再加ATP，则ATP激活电流明显增强，其电流幅值的增强作用依赖于BK及ATP浓度。BK对ATP激活电流的增强作用以增强其峰电流为主，对稳态部分增强不明显。实验观察了BK增强作用的时程，在检测的4例细胞中发现BK均于预加30s后起效，作用持续20min以上。本文结果提示：BK在初级感觉神经元水平对ATP引起的兴奋性反应可能起到一种易化作用。