动物实验学课程改革思路

运动实验学课程是我院将生理学、药理学与病理生理学实验课三合为一组成的一门独立的新课程,在组建过程中进行了一系列的实验教学结构,内容及手段方面的改革,初见成效。

动物实验学教学实践初探

我院于1998年对机能学科的实验教学进行改革，合并生理，病生，药理三科实验室，成立动物实验学教研室，三年的教学实践证明，动物实验学教学改革是成功的。

浅谈医学实验动物学教学的实践与思考

实验动物学是一门研究实验动物和动物实验科学的学科,它以实验动物为主要研究对象,并将培育的试验动物应用于生命科学等研究的一门综合性学科.简而言之,它是研究实验动物和动物实验的一门综合性学科.作为医学研究的基础课程,它成为了高等医学院学生必修的学科之一.本文介绍了动物学试验课程在教学体系、教学方法及考核等方面进行的改革和实践.通过一系列的教学改革,提高整体师资水平和教学质量,实现了资源共享.就今后实验教学进一步深化改革一开设多层次实验教学模式、建立多媒体教学体系以及对实验课教学效果的检查与评估提出了新的思路.

深化机能实验改革 全面提高医学人才素质

为适应二十一世纪医学人才的培养,我院根据特定的办学方针,将生理学、病理生理学、药理学实验课三和一组成一门独立的新课程--动物实验学.通过机能实验教学改革,提高了医学人才素质.

健脑益智方调控线粒体自噬改善APP/PS1转基因小鼠认知功能

目的 探讨健脑益智方(Jiannao Yizhi Decoction,JYD)改善认知功能的作用机制。方法 将6月龄的APP/PS1转基因小鼠按随机数字表法分为模型组、多奈哌齐组、JYD低剂量组、JYD中剂量组和JYD高剂量组,C57/BL6小鼠作为空白对照组,给药3个月后评估小鼠认知功能及线粒体自噬相关蛋白变化。结果 JYD各组均能降低逃避潜伏期(P<0.05),且JYD低剂量组的穿台次数较模型组显著增加(P<0.05)。与模型组相比,JYD中剂量和高剂量可上调PINK1的蛋白表达,差异有统计学意义(P<0.05);JYD各组均可上调Parkin的蛋白表达,差异有统计学意义(P<0.05)。与模型组相比,JYD各组均可下调p62、LC3Ⅰ的蛋白表达,差异有统计学意义(P<0.05)。结论 JYD可改善APP/PS1转基因小鼠的空间学习记忆功能,其机制可能与调节线粒体自噬有关。

Polar residual network model for assisting evaluation on rat myocardial infarction segment in myocardial contrast echocardiography

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P>0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P<0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P<0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

猩猩中年时幸福感最低

一个国际科研小组报告称，通过最新研究他们发现，尽管没有工作、婚姻和房贷等方面的压力，但黑猩猩或猩猩与人类一样会经历“中年危机”，幸福感处于一生中最低。

弥散成像在急性脑缺血性中风诊断中的价值

脑梗死发病率、致残率、致死率均比较高，是严重危害人类健康的常见病。所以，早期诊断、早期治疗问题一直是医学界的重点课题，随着影像学的不断发展，脑梗死早期诊断的敏感性和准确性有了明显提高，MRI特别是MR弥散及灌注成像被认为是诊断脑梗死最敏感的成像方法。根据不同梯度脉冲强度下水分子的扩散运动不同而设计的磁共振扩散加全成像（DWI）技术，是目前在活体组织上进行水分子扩散测量与成像的唯一方法。大量的动物实验学临床应用证明，该技术在超早期（6小时内）脑缺血性中风的定位定性诊断中具有重要的价值，

Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb ^(188)Re-HAb18

AIM:To labed Anti-hepatoma monoclonal antibody(mAb) fragment HAb18 F(ab')_2 was labeled with 188 Re for the pharmacokinetic model of ^(188)Re-HAb18 F(ab')_2 and to evaluate its pharmacokinetic parameters in hepatoma- bearing nude mice. METHODS:HAb18 F(ab')_2 was directly labeled with ^(188)Re using 2-mercaptoethanol(2-ME)as reducing agents. Labeling efficiency and immunoreactivity of ^(188)Re-HAb18 F (ab')_2 were evaluated by Whatman 3MM paper chromatography and live cell assay,respectively. Biodistribution analysis was also conducted in nude mice bearing human hepatoma in which animals were sacrificed at different time points(1,4,18,24 and 24h)after ^(188)Re-HAb18 F(ab')_2 was injected through tail-vein into hepatoma-bearing nude mice.The blood and radioactivity of organs and mass were measured.The concentrations of ^(188)Re-HAb18 F(ab')_2 were evaluated with a pharrnacokinetic 3P97 software. RESULTS:The optimum labeling efficiency and immunoreactive fraction were 91.7% and 0.78%, respectively.The parameters of ^(188)Re-HAb18 F(ab')_2 were: T_(1/2),2.29h;Vd,1.49×10^(-9)L·Bq^(-1);AUC,20.49×10~9Bq·h· L^(-1);CL,0.45×10^(-3)L·h^(-1).^(188)Re-HAb18 F(ab')_2 could locate specially in hepatoma with high selective reactivity of HAb18 F(ab')_2.^(188)Re-HAbl8 F(ab')_2 was mainly eliminated by kidney.The maximal tumor to blood ratio was at 48h,and maximal tumor to liver ratio was at 18h. CONCLUTION:The pharmacokinetics of ^(188)Re-HAb18 F(ab')_2 fit a I-compartment model.^(188)Re-HAb18 F(ab')_2 can be uptaken selectively at the hepatoma site.

Effect of Kaiyu Qingwei Jianji on the morphometry and residual strain distribution of small intestine in experimental diabetic rats

AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS： Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ- induced diabetic rats were subdivided into four groups （n = 8 in each group）, i.e. diabetic control group （DM）; high dose of KYQWJJ （T1, 36g/kg per day）; low dose of KYQWJJ （T2, 17 g/kg per day） and Gliclazide （T3, 50 mg/kg per day）. Another ten rats were used as nondiabetic control （CON）. The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS： The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment （16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 〈 0.001）. The blood glucose level in the T1 （16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P 〈 0.01） and T3 groups （16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P 〈 0.05）, but not in T2 group （P 〉 0.05） was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group （10.98 ± 1.02, 12.52 ± 1.42,13.54 ± 1.56,10.96 ± 0.96 vs 17.84 ± 2.34 pmol/L respectively, P 〈 0.05）, but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group （wet weight （g/cm）： duodenum 0.209 ± 0.012 vs 0.166 ± 0.010, jejunum 0.149 ± 0.008 vs 0.121 ± 0.004, ileum 0.134 ± 0.013 vs 0.112 ± 0.007; Wall thickness （mm）： duodenum 0.849 ± 0.027 vs 0.710 ± 0.026, jejunum 0.7259 ± 0.034 vs 0.627 ± 0.025, ileum 0.532 ± 0.023 vs 0.470 ± 0.010, all P 〈 0.05）, T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment （188 ± 11 degrees, -0.31 ± 0.02 and 0.35 ± 0.03 vs 259 ± 15 degrees, -0.40 ± 0.02 and 0.43 ± 0.05） and larger in jejunal （215 ± 20 degrees, -0.30 ± 0.03 and 0.36 ± 0.06 vs 172 ± 19 degrees, -0.25 ± 0.02 and 0.27 ± 0.02） and ileal segments （183 ± 20 degrees, -0.28 ± 0.01 and 0.34 ± 0.05 vs 153 ± 14 degrees, -0.23 ± 0.03 and 0.29 ± 0.04） in DM group than in CON group （P 〈 0.01）. TI and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment （duodenum 243 ± 14 degrees, -0.36 ± 0.02 and 0.42 ± 0.06, jejunum 180 ± 15 degrees, -0.26 ± 0.03 and 0.30 ± 0.06 and ileum 163 ± 17 degrees, -0.23 ± 0.03 and 0.30 ± 0.05, compared with DM, P 〈 0.05）. The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION： KYQWJJ （high dose） treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs

AIM： To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride （SM·HCl） on its pharmacokinetics in beagle dogs. METHODS： The in vitro release behavior of two SM·HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCI pharmacokinetics was investigated and compared. RESULTS： The optimal SM·HCl sustained-release formulation was achieved by mixing slow- and rapidrelease pellets （9：1, w/w）. The SM·HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCI sustainedrelease pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67±0.52 h vs 9.83±0.98 h and the Cmax being 1334.45±368.76 ng/mL vs 893.12±292.55 ng/mL, respectively. However, the AUC0-tn of two SM·HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM·HCl percentage absorption in vivoand the cumulative percentage release in vitro. CONCLUSION： The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.

Characteristics of liver on magnetic resonance diffusion-weighted imaging:Dynamic and image pathological investigation in rabbit liver VX-2 tumor model

AIM： To investigate dynamical and image pathological characteristics of the liver on magnetic resonance （MR） diffusion-weighted imaging （DWI） in the rabbit VX-2 tumor model. METHODS： Forty New Zealand rabbits were included in the study and VX-2 tumor piece was implanted intrahepatically. Fifteen animals received two intrahepatic implantations while 25 had one intrahepatical implantation. DWI, T1- and T2-weighted of magnetic resonance imaging （MRI） were carried out on the 7th and the 14th d after implantation and DWI was conducted, respectively on the 21th d. Ten VX-2 tumor samples were studied pathologically. RESULTS： The rate of lump detected by DWI, TlWI and T2WI was 78.7%, 10.7% and 53.5% （X^2 =32.61, P 〈 0.001） on the 7th d after implantation and 95.8%, 54.3% and 82.9% （X^2 = 21.50, P 〈 0.001） on the 14th d. The signal of most VX-2 tumors on DWI was uniform and it was equal diffusion coefficient （ADC）. did not decrease on the 7th on the map of apparent The signal of VX tumors d after implantation, most of them slowly growing during the week following implantation without significant cell dying within the tumor. VX-2 tumors grew increasingly within 14 d after implantation but the signal of most VX-2 tumors on DWI or on the map of ADC was uniform or uneven and ADC of VX tumors decreased obscurely or slightly because tumor necrosis was still not obvious. On the 21th d after implantation, the signal of most VX-2 tumors on DWI or on the map of ADC was uneven because tumor necrosis was evident and ADC of VX-2 tumor necrotic areas decreased. The areas of viable cells in VX-2 tumors manifested a high signal on DWI and a low signal on the map of ADC. The areas of dead cells or necrosis in VX-2 tumors manifested low signals on DWI and low, equal or high signals on the map of ADC but they manifested high signals on DWI and on the map of ADC at the same time when the areas of necrotic tumor became liquefied or cystic. The border of tumors on DWI appeared gradually distinct and internal signals of tumor became progressively uneven. CONCLUSION： The manifestations of viable, necrotic and liquefied or cystic areas in VX-2 tumors on DWI are typical and DWI is of significant and potential values in clinical application in both the early detection and diagnosis of liver tumors.

Resveratrol prolongs allograft survival after liver transplantation in rats

AIM： To study the immuno-modulatory effect of resveratrol （RES） on allograft rejection after liver transplantation in rats. METHODS： Male Sprague-Dawley （SD） rats were selected as donors and male Wistar rats as recipients for a rejection model. The recipients were divided into four groups after orthotopic liver transplantation （OLTx）. In the RES A, B, and C groups, RES was given intra-peritoneally once a day （25, 50, and 100 mg/kg, respectively） after OLTx, whereas in the control group, vehicle buffer was given intra-peritoneally once a day. The survival time, serum chemistry, production of cytokines, activation of transcription factor NF-kB, and histopathologic findings were then compared among these groups. RESULTS： The mean survival time after OLTx in the RES C group was significantly longer than that in the control group （16.7＋-1.2 d ,vs9.3＋-0.6 d, P〈0.01）. On the 7th posttransplant day the serum albumin level significantly improved in the RES C group, the serum total bile acid and alanine aminotransferase （ALT） levels were significantly lower in the RES C group, the serum IL-2 and INF-y levels were significantly lower in the RES C group, and the activation of transcription factor NF-kB in peripheral blood T lymphocytes was significantly suppressed in the RES A, B, and C groups in comparison to those in the control group. On the 7^th post-transplant day, a histological examination revealed apparent difference in the severity of rejection between the RES C group and control group. CONCLUSION： RES has an immuno-suppressive property as well as protective effect on hepatocytes under allograft rejection. It might serve as a novel agent for reducing the severity of hepatic allograft rejection in rats.

Histopathological comparison of topical therapy modalities for acute radiation proctitis in an experimental rat model

AIM： To evaluate the prevalent topical therapeutic modalities available for the treatment of acute radiation proctitis compared to formalin. METHODS： A total of 120 rats were used. Four groups （n = 30） were analyzed with one group for each of the following applied therapy modalities： control, mesalazine, formalin, betamethasone, and misoprostol. A single fraction of 17.5 Gy was delivered to each rat. The rats in control group rats were given saline, and the rats in the other three groups received appropriate enemas twice a day beginning on the first day after the irradiation until the day of euthanasia. On d 5, 10, and 15, ten rats from each group were euthanized and a pathologist who was unaware of treatment assignment examined the rectums using a scoring system. RESULTS： The histopathologic scores for surface epithelium, glands （crypts） and lamina propria stroma of the rectums reached their maximum level on d 10. The control and formalin groups had the highest and mesalazine had the lowest, respectively on d 10. On the 15^th d, mesalazine, betamethasone, and misoprostol had the lowest scores of betamethasone. CONCLUSION： Mesalazine, betamethasone, and misoprostol are the best topical agents for radiation proctitis and formalin has an inflammatory effect and should not be used.

CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

The distribution of motilin receptor in the amygdala of rats and its role in migrating myoelectric complex

Objective:To investigate the distribution of the motilin receptor in the amygdala of rats and its role in regulating the duodenal migrating myoelectric complex(MMC).Methods:The distribution of motilin receptor in the amygdala in adult SD rats was detected by immunohistochemistry methods,and the duodenal interdigestive MMC was recorded via the electrodes implanted in the duodenum and analyzed us- ing a multichannel recorder.Results:Motilin receptor was observed in the amygdala of rats.The great amount of motilin receptor was found in the medial amygdaloid nucleus,which was also abundant in the basolateral nucleus but less abundant in the basomedial amygdaloid nucleus,the central amygdaloid nucle- us and the lateral amygdaloid nucleus.The shortening of the duodenal MMC cycle duration and the in- crease of the amplitude and the frequency of phase $ were recorded after motilin receptors being bound with exogenous motilin in the amygdala.The effects could be completely blocked by the subdiaphragmatic vagotomy but not by the intravenous injections of atropine,phentolamine or propranolol.Anti-motilin serum could partially block these effects,and the destruction of the basolateral nucleus of the amygdala had no significant effects on the duodenal MMC.Conclusion:Motilin receptor is present in all the subnu- clei of the amygdala,with the greatest amount of motilin receptor present in the medial amygdaloid nucle- us.Microinjections of motilin in the amygdala can shorten the duodenal MMC cycle duration and increase the amplitude and the frequency of phaseⅢ.These effects might be accomplished via the amygdala-hy- pothalamus-brainstem-vagus pathway,indicating the important role of the amygdala motilin receptor in the duodenal MMC regulation.

High incidence of inflammatory bowel disease with improved hygiene and failure to get human-like IBD in laboratory animals

Inflammatory bowel disease （IBD） has emerged and dramatically increased in the last century with its cause remaining largely unknown. Extensive studies have been conducted, and many of them involved animal experiments. To date, an animal model that exactly replicates human IBD is still lacking.

Kinetics of Photocatalytic Degradation of Gaseous Organic Compounds on Modified TiO_2/AC Composite Photocatalyst

This study is focused on the kinetic characteristics of photocatalytic degradation of gaseous organic compounds on modified titanium dioxide/activated carbon composite photocatalyst(MTA).The MTA,which co-doping with iron(Fe) and nitrogen(N),was synthesized by a sol-gel method,and its photocatalytic performance was investigated under different reaction conditions.The experimental data obtained were tested by the zero,first and second order kinetic model,and the factors affecting the kinetic model were analyzed.It was clearly demonstrated that the experimental data of toluene and acetone on MTA fit quite well with second order kinetic model equation,but the experimental data of formaldehyde fits well with zero order kinetic model equation.