介绍西安交通大学医学部药理学系开展留学生药理学实验教学改革的措施,包括编写统编双语教材,举办机能实验操作技能大赛,开展案例式教学、小组式学习、讨论式学习等.这一教学改革成效显著,提高了留学生实验课参与率、实验动手能力、自主学习能力以及团队合作意识.

目的 探讨不同浓度米氮平对慢性束缚应激导致的青春期小鼠焦虑、抑郁样行为的改善作用,为青春期情绪障碍的治疗提供研究资料.方法 随机选取60只出生3～4周龄雄性C57小鼠,模型组给予连续10 d(4 h/d)束缚应激(CRS),治疗组分别连续腹腔注射低浓度(15 mg/kg)或高浓度(30 mg/kg)米氮平(10 d).分别采用矿场实验(OFT)检测焦虑样行为,悬尾实验(TST)和强迫游泳实验(FST)检测抑郁样行为,酶联免疫法检测血清米氮平水平.结果 OFT实验中,CRS小鼠在中央区停留时间为(106.1±36.64)s,低于对照组[(182.5±38.69)s](P＜0.01),应用高浓度米氮平(30 mg/kg)后该时间延长至(186.1±23.43)s,接近正常水平.TST实验中,CRS组静止时间为(176.2±104.5)s,高于对照组[(71.05±36.4)s](P＜0.01),应用高浓度米氮平(30 mg/kg)后时间缩短为(69.13±31.72)s(P＞0.05).FST 实验中,CRS组的漂浮时间为(304.6±87.96)s,高于对照组[(196.2±72.6)s](P＜0.01),应用高浓度米氮平(30 mg/kg)后,漂浮时间缩短为(188.8±49.05)s(P＞0.05).CRS导致小鼠血清 NE[(34.52±9.03)pg/ml)]和5-HT[(44.42±16.55)ng/ml]水平低于正常小鼠(P＜0.01),应用高浓度米氮平后恢复接近正常水平[NE:(105.93±21.42)pg/ml,5-HT:(133.56±32.31)ng/ml].结论 CRS可以造成青春期小鼠抑郁和焦虑样情绪障碍,全身慢性应用高浓度米氮平可改善其焦虑和抑郁的症状.

目的 探讨瘦素处理对慢性束缚应激(CRS)造成的青春期小鼠焦虑样行为的影响,为青春期情绪障碍的治疗提供研究资料.方法 选取50只21～30 d龄小鼠,连续10 d低强度(2 h)/高强度(4 h)束缚应激,高架十字迷宫(EPM)和矿场实验(OFT)观察大鼠焦虑样行为,酶联免疫法检测血清瘦素水平.结果 高强度束缚(HCRS)组小鼠血清瘦素含量为(4.2±1.3) pg/ml,低于对照组小鼠[(10.4±2.9)pg/ml](P＜0.05).EPM实验中,HCRS小鼠在开放臂停留时间和进入开放臂次数分别为(68.5±18.9)s和1.7±1.1,少于正常组小鼠[(101.3±19.8)s,3.8±1.8,P＜0.01],而瘦素处理后,这两个指标分别升高至(93.8±16.4)s和3.3±1.6,接近正常水平.OFT实验中,HCRS小鼠在中央区停留时间为(63.4±15.9)s,低于对照组[(142.5±20.2)s,P＜0.01],应用瘦素后该时间延长至(130.5±26.5)s.而低强度束缚小鼠在这两个实验中的各指标均未出现明显改变.结论 HCRS可以造成青春期小鼠的焦虑障碍,慢性瘦素应用提高了血清瘦素含量,改善了焦虑症状.

机能实验学课程为学生提供了基本动物实验操作训练,建立了初步的科研思维.结合课堂教学,开展了开放式课题研究、制作课程思维导图以及即时课题训练等活动,将课堂与课外相结合,多角度、多层面地培养学生的主动探索意识,提升逻辑思维能力,激发科研热情和兴趣,为培养更加全面和优秀的医务工作者打好基础.

Ideological and political education is an important component of college educations which not only meets the needs of China's current national conditions, but also is of great significance to promote the comprehensive development of contemporary college students. Functional experiment course is a basic medical practice training, so students contact the early stage of university education. According to the characteristics of medical students and its specialty, the ideological and political elements, such as patriotism education, medical moral education, life education, legal education and team-work spirit in medical functional experiment course were excavated, meanwhile, the approaches and methods of smart integration between medical functional experiment course and ideological and political education through curricula was explored. Based on the above ideological and political education through curricula teaching system suitable for functional experiment training was constructed, so as to better promote the unity of knowledge transmission, skills training and values shaping in students.

为了客观了解我校课程思政在机能实验教学中开展实施以来的思政效果、学生评价、不足及建议,以进一步提高课程思政质量.本研究于2019年11月在我校机能实验课结束时开展“医学生对课程思政在机能实验学教学中的评价”问卷调查,西安交通大学医学部2017级部分专业305名学生通过线上方式填写调查问卷.结果 发现90.8％的学生分别认为“课程思政”对塑造学生正确的人生观、世界观、价值观有帮助;91.2％以上的学生对专业课教师思政内容教学感到满意;85.3％的学生喜欢混合模式“课程思政”的教学方式;通过调查问卷发现的问题如法制教育、诚信科研等思政效果有待于提高,个别专业教师课程思政融入技巧亟待改进.研究发现医学生对“课程思政”在机能实验教学中的开展满意度较高,但仍有提升空间,可以通过加强教师素质,丰富思政内容,开展灵活多样的思政教学方式等提高思政效果.

目的 观察不同强度的运动训练对青春期大鼠学习记忆能力的影响以及和血清瘦素水平的关系,为研究青春期学习记忆能力的提高提供依据.方法 选择30只45～50日龄大鼠,随机分为低强度运动组、中等强度运动组和对照组,每组10只,连续一周低强度或中等强度跑台运动训练,Morris水迷宫观察大鼠学习记忆,酶联免疫法检测血清瘦素(Lep)水平.结果 中等强度运动训练组大鼠Morris水迷宫实验四个象限的平均逃避潜伏期分别为(44.8±5.0)s,(49.3±5.2)s,(39.3±4.7)s和(37.7±2.8)s,均短于正常组大鼠(P＜0.01),中等强度运动训练组大鼠穿越站台次数为5.2±1.8,高于正常组大鼠(2.6±0.4),差异均具有统计学意义(P＜0.01).中等强度运动组大鼠的血清Lep水平[(15.1±4.5) pg/ml]高于正常组大鼠[(12.8±3.7) pg/ml](t=2.47,P＜0.05).结论 中等强度的运动训练能够提高青春期大鼠的学习记忆能力,这可能与血清Lep含量的增加有关.

Chronic islet inflammation is associated with development of type 2 diabetes mellitus (T2DM). Intermediate-conductance calcium-activated K+ (KCa3.1) channel plays an important role in inflammatory diseases. However, the role and regulation of KCa3.1 in pancreatic β cells in progression of T2DM remain unclarified. In the present study, we evaluated the effect of the specific KCa3.1 channel blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) on diabetic phenotype in the db/db model. In diabetic mice, blockade of KCa3.1 significantly improved glucose tolerance, enhanced secretion of postprandial insulin level, and reduced loss of β-cell mass through attenuating the expression and secretion of inflammatory mediators. Furthermore, in cultured pancreatic β cells, exposure to high levels of glucose or palmitic acid significantly increased expression and current density of the KCa3.1 channel as well as secretion of proinflammatory chemokines, and the effects were similarly reversed by preincubation with TRAM-34 or a NF-κB inhibitor pyrrolidinedithiocarbamate. Additionally, expression of KCa3.1 in pancreas islet cells was up-regulated by activation of NF-κB with IL-1β stimulation. In summary, up-regulated KCa3.1 due to activation of NF-κB pathway leads to pancreatic inflammation via expression and secretion of chemokines and cytokines by pancreatic β cells, thereby facilitating progression of T2DM.-Pang, Z.-D., Wang, Y., Wang, X.-J., She, G., Ma, X.-Z., Song, Z., Zhao, L.-M., Wang, H.-F., Lai, B.-C., Gou, W., Du, X.-J., Deng, X.-L. KCa3.1 channel mediates inflammatory signaling of pancreatic β cells and progression of type 2 diabetes mellitus.

目的:探讨虚拟现实(Virtual Reality,VR)技术在基础医学实验教学中的应用和效果.方法:以西安交通大学2016级医学专业本科生为研究对象,进行问卷调查,记录学生参与VR实验的情况,并比较其真实操作成绩.结果:大部分学生对VR技术了解,但接触频率较低;学生对VR实验教学感兴趣(95.09％),对VR教学整体满意度较高(96.74％);VR实验教学有助于提高学生真实实验操作成绩.结论:VR实验教学有一定的新颖性,能够提高学生学习兴趣,也有利于学生真实实验操作和训练.

为探讨TBL结合虚拟实验教学模式在医学机能实验学教学中的应用及效果,选取80名临床医学专业本科生,随机分为实验组(38人)和对照组(42人).实验组采用TBL结合虚拟实验教学模式,对照组采用传统讲授模式.结果显示实验组理论笔试平均成绩(78.45±9.88分)高于对照组(72.31±13.83分),差异有统计学意义(P<0.05).问卷调查显示,实验组90％的学生接受和认可TBL结合虚拟实验教学模式.TBL结合虚拟实验教学模式能提高机能实验学的教学效果.

Background-Cardiac fibrosis is a core pathological process associated with heart failure. The recruitment and differentiation of primitive fibroblast precursor cells of bone marrow origin play a critical role in pathological interstitial cardiac fibrosis. The K(Ca)3.1 channels are expressed in both ventricular fibroblasts and circulating mononuclear cells in rats and are upregulated by angiotensin II. We hypothesized that K(Ca)3.1 channels mediate the inflammatory microenvironment in the heart, promoting the infiltrated bone marrow-derived circulating mononuclear cells to differentiate into myofibroblasts, leading to myocardial fibrosis. Methods and Results-We established a cardiac fibrosis model in rats by infusing angiotensin II to evaluate the impact of the specific K(Ca)3.1 channel blocker TRAM-34 on cardiac fibrosis. At the same time, mouse CD4(+) T cells and rat circulating mononuclear cells were separated to investigate the underlying mechanism of the TRAM-34 anti-cardiac fibrosis effect. TRAM-34 significantly attenuated cardiac fibrosis and the inflammatory reaction and reduced the number of fibroblast precursor cells and myofibroblasts. Inhibition of K(Ca)3.1 channels suppressed angiotensin II-stimulated expression and secretion of interleukin-4 and interleukin-13 in CD4(+) T cells and interleukin-4- or interleukin-13-induced differentiation of monocytes into fibrocytes. Conclusions-K(Ca)3.1 channels facilitate myocardial inflammation and the differentiation of bone marrow-derived monocytes into myofibroblasts in cardiac fibrosis caused by angiotensin II infusion.

随着我国医学教育与国际的接轨,人体功能学实验教学逐渐得到认可和重视,越来越多的医学院校正在逐步开展相关教学.西安交通大学人体功能实验教学在我国开展较早,课程体系较为完善,本文较系统地介绍了人体功能实验教学的意义、教学目标、实验室构建、课程内容设置、第二课堂开展,以及对相关问题的思考,供同行借鉴指正,以期为提高我国医学实践教学,探索更多的途径.

Background/Aims: Atherosclerosis is a chronic inflammatory disease in the artery walls. Fibrinopeptide A (FPA) is a biomarker of the activation of coagulation system, and a high concentration of FPA in blood occurs in patients with ischemic heart disease etc. However, there exist few studies on the pathological effects of FPA in cardiovascular system. Therefore, the present study examined the effect of FPA on CRP expression in VSMCs and the molecular mechanisms. Methods: mRNA and protein expression was identified by quantitative real-time PCR and Western blot, respectively. Reactive oxygen species (ROS) and the immunofluorescence staining were observed by a fluorescence microscope. Plasma FPA and CRP level was determined by ELISA. Results: FPA induced the expressions of CRP, IL-1β and IL-6 in VSMCs, and anti-IL-1β and anti-IL-6 neutralizing antibodies partially reduced FPA-induced CRP expression in VSMCs. The subchronic administration of FPA to rats increased FPA level in plasma and CRP expression in the aortic artery walls. The further studies showed that FPA promoted superoxide anion generation in VSMCs. Antioxidant NAC antagonized FPA-stimulated superoxide anion generation and inhibited FPA-induced CRP expression in VSMCs. FPA activated ERK1/2 and p38 phosphorylation, and PD98059 and SB203580 reduced FPA-induced CRP expression. Moreover, NAC inhibited the activation of ERK1/2 and p38. In addition, FPA enhanced NF-κB level in the nuclei of VSMCs, and PDTC reduced FPA-induced expression of CRP. Conclusions: FPA induces CRP expression in VSMCs via ROS-ERK1/2/p38-NF-κB signal pathway. This finding for the first time provides an experimental evidence for pro-inflammatory effect of FPA.

生理学是研究生物体及其各组成部分功能活动和规律的科学,是生物学科的一个分支.它同时也是临床各学科及科学研究的基础课程之一,起重要的枢纽作用.将互动式教学法运用于高校生理学理论课教学是现代教学方法改革的一种新趋势,也是生理学教学改革发展的迫切需求.文章介绍了在生理学理论课和实验课教学中,如何更好地融合传统教学模式和互动式教学模式,以提高教学质量.

Objective To investigate the protective effects of Xinxinshu Capsules on experimental myocardial infarction in rats in‐duced by left anterior descending branch of coronary artery .Methods Left anterior descending coronary arteries of rats were ligated to produce acute myocardial infarction model .Immunohistochemisty was used to detect the contents of VEGF ,bFGF ,Ⅷ factor and vascular density in the edge of infarct section ,and the infarct area was measured .Results The infarct areas in treatment groups were obviously less than in model group .The contents of VEGF ,bFGF and Ⅷ factor in the edge of infarct section and vascular density in treatment groups were significantly increased compared with those in model group .Conclusion Xinxinshu Capsules can decrease the infarct area and stimulate angiogenesis of the collateral branch of coronary artery in ischemic myocardium of rats ,and showed good protective effect on myocardial ischemia .

Objective To study the effects of different doses of Xianchan Tablets on arrhythmia in rats .Methods After intragastric administration of different doses of Xianchan Tablets to rats ,heart rate and arrhythmia of rats were recorded within 2 hours .The maximum dosage of Xianchan Tablets was also tested by intragastric administration .Results The Xianchan Tablets with the dose 0 .2 and 0 .3 g?kg -1 did not affect the heart rate and arrhythmia in rats .The Xianchan Tablets with doses of 0 .45 ,0 .68 and 1 .01 g?kg -1 could increase the heart rate in rats ,and booste arrhythmia incidence rate with 20% ,70% and 100% ,respectively .The bufonis venenum with the dose of 0 .012 g?kg -1 could increase the heart rate and arrhythmia incidence rate up to 30% .The maximum dosage of Xianchan Tablets was 7 .2 g?kg-1 ,which was approximately 14 .4 times corresponding to person dosage (0 .5 g?kg -1 ) . Conclusion The Xianchan Tablets were safe within the dose of 0 .3 g?kg -1 (corresponding to person dosage 3 g per day) .

针对临床医学八年制学生的特点及该专业培养的目标，探讨了八年制机能实验教学模式特点及应该注意的事项。在八年制学生的机能实验教学中引入开放性实验教学理念不仅有利于激发学生自主学习的积极性和主动性，而且有利于学生探索未知事物的兴趣，使得其团队精神、创新能力得到培养。除此之外，本文还对引入开放式实验教学应注意的问题进行了探讨。

Objective To investigate the characteristics of the slope of dynamic restitution curve,S1S2 restitution curve and short-term memory response in both endocardium and epicardium of rabbit left ventricle along with pacing rate.Methods Eight isolated arterially perfused rabbit left ventricular wedge preparations were used in this study.Transmural ECG and action potential duration(APD) were recorded simultaneously.And all APDs of every heart beats were measured over the whole experiment.The modified perturbed down sweep pacing protocol(PDP)was applied to the endocardial apex at basic cycle lengths(BCL0) of 2 000 ms.Then the restitution portrait(RP) was measured over a range of BCL1 from 600 to 300 ms.The RP in rabbit endocardial and epicardial sites was investigated whether there was transmural heterogeneity in the restitution properties.Results Both dynamic restitution curve(RC) and S1S2 restitution curve(RC) slopes showed the same tendency,which were increased as BCL1 changed from 600 to 300 ms.And with this study protocol,the slopes from endocardial region were steeper at 500,400,and 300 ms than that from epicardial region(P<0.05).Furthermore,the transient state short-term memory reflected by the value α was measured,which was equal to the slope of dynamic RC subtracting the slope of local S1S2 RC when abrupt adding a premature and postmature beat.The α value was dependent on location measured,with larger α value in endocardium at BCL1=500,400,300 ms than that in epicardium(P<0.05).Conclusions The results demonstrate that the spatial heterogeneity of the short-term memory exists between endocardium and epicardium,with steeper slope of dynamic RC,S1S2 RC,and stronger short-term memory response in endocardial region.It might be a partial mechanism that vulnerable window for unidirection conduction block induced by premature beat located at endocardial site is wider and more likely to induce ventricular arrhythmias.

Objective To investigate the effect of flecainide on the cardiac contractility and electrical activity in rabbit left ventricular.Methods Isolated arterially perfused rabbit left ventricular wedge preparations were used with stimulus at basic cycle length(BCL) of 2 000,1 000,and 500 ms,respectively.The cardiac contractility and transmural ECG QRS complex,QT interval,the interval from the peak of the T wave to the end of T wave(Tp-e),and Tp-e/QT ratio were recorded simultaneously without flecainide or with flecainide at 0.3,1,3,6,and 10μmol/L. Results The cardiac contractile force was increased proportionally with stimulating rate.However,along with the increasing concentration of flecainide,cardiac contractile force became weaker progressively and 10μmol/L flecainide could cause the contractility even weaker at BCL of 500 ms than that at BCL of 1 000 ms.The QRS duration kept stable at all stimulating rate in control.However,QRS duration got widening gradually in a use-dependent manner with the flecainide concentration increase.10 μmol/L flecainide could make QRS alternans and ventricular tachycardia or ventricular fibrillation at BCL of 500 ms.Flecainide did not show significant effect on QT and Tp-e intervals as well as Tp-e/QT ratio.Conclusion Flecainide could decrease electrical activity conduction and reverse positive inotropic effect of staircase,which could be the important mechanism for arrhythmoginic effect.

Caulophine is a new fluorenone alkaloid isolated from the radix of Caulophyllum robustum MAXIM and identified as 3-(2-(dimethylamino) ethyl)-4,5-dihydroxy-1,6-dimethoxy-9H-fluoren-9-one. Due to its new chemical structure, the pharmacological activities of caulophine are not well characterized. The present study evaluated the protective effect and the primary mechanisms of caulophine on cardiomyocyte injury. Viability of cardiomyocytes was assayed with the MTT method, and cell apoptosis was detected by flow cytometry. Myocardial infarction was produced by ligating the coronary artery, and myocardial ischemia was induced by isoproterenol in rats. Myocardial infarction size was estimated with p-nitro-blue tetrazolium staining. Lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), and free fatty acid (FFA) were spectrophotometrically determined. Histopathological and ultrastructural changes of ischemic myocardium were observed. The results showed that pretreatment with caulophine increased the viability of H2O2-and adriamycin-injured cardiomyocytes; decreased CK, LDH, and MDA; increased SOD; and inhibited H2O2-induced cellular apoptosis. Caulophine reduced myocardial infarct size and serum CK, LDH, FFA, and MDA; raised serum SOD; and improved histopathological and ultrastructural changes of ischemic myocardium. The results demonstrate that caulophine has the ability to protect cardiomyocytes from oxidative and ischemic injury through an antioxidative mechanism that provides a basis for further study and development of caulophine as a promising agent for treating coronary heart disease.