Modulating Effects of Chlorogenic Acid on Lipids and Glucose Metabolism and Expression of Hepatic Peroxisome Proliferator-activated Receptor-α in Golden Hamsters Fed on High Fat Diet

Objective To examine the effects of chlorogenic acid （CGA） on lipid and glucose metabolism under a high dietary fat burden and to explore the possible role of peroxisome proliferator-activated receptor-α （PPAR-α） in these effects. Methods Twenty male golden hamsters were randomly divided into CGA treatment group （n=10, given peritoneal injection of CGA solution prepared with PBS, 80 mg CGA/kg body weight daily）, and control group （n=10, given PBS i.p. at the average volume of the treatment group）. Animals in both groups were given 15% high fat diet. Eight weeks after treatment with CGA, the level of biochemical parameters in fasting serum and tissues and the expression of hepatic mRNA and protein PPAR-α were determined. Results Eight weeks after treatment with CGA, the levels of fasting serum triglyceride （TG）, free fatty acid （FFA）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, glucose （FSG）, and insulin （FSI） were significantly lower in the GGA treatment group than in the control group. CGA also led to higher activity of hepatic lipase （HL） lower contents of TG and FFA in liver, and lower activity of lipoprotein lipase （LPL） in skeletal muscle. Furthermore, CGA significantly elevated significantly elevated the expression level of mRNA and protein expression in hepatic PPAR-α. Conclusion CGA can modify lipids and glucose metabolism, which may be attributed to PPAR-α facilitated lipid clearance in liver and improved insulin sensitivity.

Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene （DMBA）-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group （n=5） and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA （0.5% in acetone） to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group （n=30）, untreated prem＇alignant lesion group （n=10） and normal saline （NS）-treated group （n=10）. The cheek （buccal） pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic （SEM） analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic （TEM） analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. Conclusion Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

Postnatal development of NADPH-diaphorase expression in the visual cortex of the golden hamster

Nitric oxide is an important neuromodulator in the brain and is involved in the development of visual system. But it is not clear how nitric oxide and nitric oxide synthase （NOS） are involved in the developing visual cortex of rodents. Thus we examined the expression of NOS activity in the postnatal developing visual cortex of the golden hamster by using histochemical technique for NADPH-diaphorase （NADPH-d）. A heavily stained NADPH-d band was observed in the neuropil of the visual cortex. This NADPH-d band initially appeared in the cortical plate from the day of birth （P0） to postnatal day 4 （P4）. From P7 to P21, this band was confined to area 17 and migrated to the deeper layers Ill IV and V VI before it eventually disappeared at P28. Such developmental trends of the band correlated well with the process of formation and establishment of the geniculo-cortical projection patterns. Thus, the areal specific development of the band suggests that NOS is closely related to the cortical differentiation and synaptic formation of the primary visual cortex. On the other hand, monocular eye enucleation on P1 could not alter the appearance of this NADPH-d positive band, indicating a non-activity dependant role of NOS. In addition, differences in the laminar distributions and developmental sequence between the heavily and lightly stained NADPH-d positive neurons during development suggest that they play different roles in the development.

Effect of Cholesterol Content in Diet on Atorvastatin(ATO)-induced Liver Injury in Golden Hamsters

[Objectives]The objective of this study was to investigate the effect of cholesterol content in high-fat diet on atorvastatin(ATO)-induced liver injury in golden hamsters and compare the degree of liver injury caused by two high-fat diets with different cholesterol proportions.[Methods]Male golden hamsters were randomly and evenly divided into different groups and given different high-fat diets for 14 consecutive days by gavage to establish hyperlipidemia models.From the 15th d on,the hamsters in the model groups were given ATO at a dose of 5 mg/kg,one a day,for 9 consecutive days.Blood was sampled from the orbital veins of the hamsters for the determination of biochemical indicators.Liver tissues of the hamsters were sampled,paraffin-embedded,sliced,stained by HE(hematoxylin-eosin)method and observed under an optical microscope.[Results]Compared with standard diet group,the body weight increased significantly(P<0.05),the serum TC,TG and LDL-C levels increased significantly(P<0.05),the serum HDL-C level declined significantly(P<0.05),and the ALT and AST levels increased significantly(P<0.05)in the high-fat diet groups.This trend was more obvious in the high-fat II group than the high-fat I group.After ATO intervention,the HDL-C,TBIL and TBA levels increased significantly(P<0.05),and the liver ALT and AST levels further increased(P<0.05)in the model groups.This trend was more obvious in the model II group than the model I group.The morphological inspection shows that the fat deposition in the liver tissues was severe;the hepatocytes in the model groups were obviously damaged;the liver injury in the hamsters fed high-fat diet containing 0.2%cholesterol and intervened with ATO was relatively mild but severer than the high-fat diet groups.[Conclusions]Hamster models of hyperlipidemia were successfully established in this study.High-fat diet could cause liver injury.While lowering blood lipid level,ATO aggravated liver injury.Among the high-fat diets with different proportions of cholesterol,the diet containing 0.2%cholesterol had little effect on ATO-induced liver injury.

FURTHER STUDIES ON THE MALIGNANT TRANSFORMATION OF SYRIAN GOLDEN HAMSTER EMBRYO CELLS IN VITR0 BY THORIUM DIOXIDE AND RARE EARTH IRON MINERAL DUSTS

Malignant transformation of hamsterembryo cells was induced in vitro by rareearth iron mineral dusts(MP),naturalthorium(Th02) and MP plus Th02.Dusts of MP,MP plus Th02 or Th02 were added into themedium with the final concentration of 17.0,

EXPERIMENTAL STUDY ON MICROWAVE RADIATION IN BLOCKING LEUKOPLAKIA FROM CANCERATION IN GOLDEN HAMSTER CHEEK POUCH

Objective Lately, microwave radiation (MR) has been successfully used to cure a variety ofdiseases including oral mucosal diseases and oral tumors in stomatology. Preventive MR of precancerous lesionsfrom canceration is the goal of this study which had been rarely reported. Methods Between leukoplakia modelanimals and MR treated model animals, the cancer incidences were compared and the macroscopic and microscopicpathology were detailed. The functional parameters of the microwave apparatus were analysed to yield the optimumdata for future clinical use. Results The cancer blocking effect of MR was proved by the incidence of canceration3.5 times less frequent in MR treated animals. Conclusion Analysis of the macroscopic and microscopicpathology may disclose the mechanism of the therapeutic MR.

Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters

Most studies support the viewpoint that the vomeronasal organ has a profound effect on conspecific odor recog­nition,scent marking and mating behavior in the golden hamster(Mesocricetus auratus).However,the role of the vomeronasal organ in social odor recognition,social interaction and fitness is not well understood.There­fore,we conducted a series of behavioral and physiological tests to examine the referred points in golden ham­ster.We found that male hamsters with vomeronasal organ lesion showed no preference between a predator odor(the anal gland secretion of the Siberian weasels(Mustela sibirica)and putative female pheromone components(myristic acid and palmitic acid),but were still able to discriminate between these 2 kinds of odors.In behavior­al tests of anxiety,we found that vomeronasal organ removal causes female hamsters to spend much less time in center grids and to cross fewer center grids and males to make fewer crossings between light and dark boxes than sham-operated controls.This indicates that a chronic vomeronasal organ lesion induced anxious responses in females.In aggressive behavioral tests,we found that a chronic vomeronasal organ lesion decreased agonistic behavior in female hamsters but not in males.The pup growth and litter size show no differences between the 2 groups.All together,our data suggested that vomeronasal organ ablation disrupted the olfactory recognition of social chemosignals in males,and induced anxiety-like and aggressive behavior changes in females.However,a vomeronasal organ lesion did not affect the reproductive capacity and fitness of hamsters.Our studies may have important implications concerning the role of the vomeronasal organ in golden hamsters and also in rodents.

Characterization of SHARPIN knockout Syrian hamsters developed using CRISPR/Cas9 system

Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.

基于肠道菌群探讨粗壮女贞总苷对高脂血症金黄仓鼠的降脂作用机制

目的评价粗壮女贞总苷(total phenylpropanoid glycosides extracted from Ligustrum robustum(Roxb.)Blume,LRTPG)对高脂血症金黄仓鼠的降脂作用并探讨其对肠道菌群的调节作用。方法60只仓鼠随机分为对照组、模型组、阳性药组、LRTPG-L组、LRTPG-M组、LRTPG-H组。高脂饲料诱导造模成功后连续给药4周,进行血脂和肝脂含量检测,并采集对照组、模型组和LRTPG-H组仓鼠结直肠部位成形粪便进行16S rDNA测序。结果LRTPG对高脂血症仓鼠具有降低血清TG、TC、LDL-C水平和肝脏TG、TC含量的作用。肠道菌群测序结果显示,与模型组比较,LRTPG在门水平降低厚壁菌门相对丰度,增加拟杆菌门和疣微菌门相对丰度(P<0.01);科水平上明显升高克里斯滕森菌科、消化球菌科、疣微菌科相对丰度(P<0.05或P<0.01);属水平上明显升高颤螺菌属、颤杆菌克属、解黄酮菌属和阿克曼氏菌属的相对丰度(P<0.05或P<0.01)。这些菌群的变化均有益于LRTPG降脂作用的发挥。结论LRTPG可能通过改善高脂饮食导致的金黄仓鼠肠道菌群紊乱发挥降脂功效。

复方石榴皮药膜对金黄地鼠皮脂腺斑形态学及雄激素受体表达的影响

目的:观察复方石榴皮药膜对金黄地鼠皮脂腺斑大小、组织形态及雄激素受体的影响,探讨其在痤疮治疗中的作用机制。方法:将15只天生具有雄激素依赖性的雄性金黄地鼠随机分为空白组、阳性对照组、药膜组,每组5只。分别于两侧皮脂腺斑处涂抹蒸馏水、0.025%维A酸乳膏、复方石榴皮药膜,连续给药28 d,于第0、14、28天测量金黄地鼠双侧皮脂腺斑面积大小并取部分皮脂腺斑行组织病理检测,免疫组织化学检查雄激素受体(AR)表达水平。结果:药膜组给药第14、28天分别与给药前比较,皮脂腺斑面积减小,差异均有统计学意义(P<0.05)。阳性对照组给药第28天与给药第14天比较,皮脂腺斑面积减小,差异有统计学意义(P<0.05)。给药第28天,药膜组与阳性对照组皮脂腺斑面积大小比较,差异有统计学意义(P<0.05)。给药第28天,与空白组比较,药膜组、阳性对照组皮脂腺斑厚度减小,差异均有统计学意义(P<0.05);药膜组、阳性对照组皮脂腺斑AR表达减少,差异均有统计学意义(P<0.05)。结论:复方石榴皮药膜可减小金黄地鼠痤疮模型皮脂腺斑面积、减轻皮脂腺斑厚度,其作用机理可能与抑制雄激素受体表达有关。

真孕受体用于金黄仓鼠胚胎移植的方法建立与优化

目的 优化金黄仓鼠胚胎移植技术,探索金黄仓鼠真孕受体最佳移植胚胎数目及发育时期。方法 建立真孕白化金黄仓鼠种群作为胚胎移植受体,比较胚胎发育期、受体减胚及二次移植受体对产仔率、供胚得仔率及后代存活率的影响,确定真孕受体最佳胚胎移植枚数及移植方法。结果 相对于野生型金黄仓鼠作为移植受体,真孕白化受体可快速判定子代来源,并适用于多种以胚胎移植为基础的生殖类实验方案,采用受精卵或二细胞胚胎对移植效果无显著影响(P>0.05);减胚组能显著提高供胚得仔率(22%,P<0.05),二次移植受体的未孕率显著提高(42%,P<0.01);移植6~10枚胚胎的供胚得仔率最高(27%,P<0.01),存活率正常(89%)。结论 6~10枚供体胚胎有助于提高供胚得仔率和存活率,基于白化真孕受体的胚胎移植方法,为金黄仓鼠的应用与开发提供了技术支撑。

噪声对SPF级金黄地鼠繁殖性能的影响

为了检测噪声对SPF级金黄地鼠繁殖性能的影响,试验首先将48只饲养在≤60 dB(A)噪声环境中的10周龄金黄地鼠随机分为60 dB(A)以下组、60~70 dB(A)组、80~90 dB(A)组、100~110 dB(A)组,每组雄鼠和雌鼠各6只并按1∶1比例合笼直到分娩,每天08:30—11:30在相应的噪声环境中暴露3 h,连续25 d,计算各组妊娠率、单只孕鼠平均产崽数和幼崽5日龄存活率。然后将20只饲养在≤60 dB(A)噪声环境中距分娩还有1~3 d的金黄地鼠随机分为60 dB(A)以下组、60~70 dB(A)组、80~90 dB(A)组、100~110 dB(A)组,每组5只,幼崽从出生到10周龄每天08:30—11:30分别置于相应的噪声环境中暴露3 h,计算幼崽存活率;幼崽10周龄时,摘除眼球采血并采用ELISA法检测血清抗缪勒管激素、抑制素B含量,采用计算机辅助精子分析系统检测雄鼠精子活力和精子的曲线速度、直线速度和平均路径速度,计算睾丸指数和卵巢指数,制作睾丸和卵巢的石蜡切片并进行H.E.染色,观察睾丸和卵巢的组织病理学变化;在每组幼崽中选取非近亲关系的雄鼠和雌鼠各5只,按1∶1比例进行组内交配,计算各组妊娠率、单只孕鼠平均产崽数和幼崽5日龄存活率。结果表明:从雄雌合笼到分娩,各组妊娠率、单只孕鼠平均产崽数和幼崽存活率均差异不显著(P>0.05)。幼崽从出生到10周龄,80~90 dB(A)组、100~110 dB(A)组的幼崽存活率均显著低于60 dB(A)以下组(P<0.05)。幼崽10周龄时,各组抗缪勒管激素含量、抑制素B含量、睾丸指数、卵巢指数、精子的曲线速度、直线速度、平均路径速度、妊娠率、单只孕鼠平均产崽数和幼崽5日龄存活率均差异不显著(P>0.05);100~110 dB(A)组精子活力极显著低于其他组(P<0.01);除60 dB(A)以下组外,其他各组睾丸出现间质稀疏、生精细胞排列紊乱、空泡化等不同程度的病理变化,卵巢中的闭锁卵泡数量增多,80~90 dB(A)组可见次级卵泡和成熟卵泡。幼崽组内交配后,各组妊娠率、单只孕鼠平均产崽数和幼崽5日龄存活率均差异不显著(P>0.05)。说明金黄地鼠从出生开始每天08:30—11:30暴露于噪声环境中3 h,噪声超过80 dB(A)会影响睾丸和卵巢的组织形态结构,噪声超过100 dB(A)会显著降低精子活力。

无菌金黄地鼠模型建立

目的使用剖宫产净化(cesarean section purification)方法建立无菌金黄地鼠模型。方法供胎母鼠选择SPF级金黄地鼠,雌雄按1∶1进行交配,见栓后与雄鼠分开饲养。代乳母鼠的合笼时间应早于供胎母鼠一周。怀孕的金黄地鼠临产时在超净工作台内进行子宫摘除术,传入净化用隔离包内,剥离子宫获得待净化乳鼠,分别使用无菌级ICR小鼠和无菌级SD大鼠进行代乳,成功离乳后转入饲养用隔离包内。每月对饲养用隔离包进行无菌状态检测。结果共实施3次剖宫产手术,第1次和第2次代乳失败,第3次代乳成功,获得仔鼠18只,存活率88%,离乳存活率66%,依照GB/T 14926.41-2001进行无菌金黄地鼠状态检测均为合格。结论通过剖宫产净化技术,使用无菌级ICR小鼠和无菌级SD大鼠进行代乳,达到微生物净化目的,获得无菌化金黄地鼠模型。

不同固定液对光镜下金黄地鼠海马体神经元的影响

目的比较不同固定液对光镜下金黄地鼠海马体神经元的影响,为金黄地鼠海马体神经元固定液的选择提供参考。方法将21只11周龄雄性SPF级金黄地鼠随机分为7组,分别使用4%多聚甲醛、10%中性甲醛、Bouin’s、Carnoy、Davidson’s、Zenker、Helly溶液进行心脏灌注,剥离脑壳取出完整大脑,在对应的固定液中固定48 h,并制作成石蜡切片,经HE染色后在光镜下观察海马体神经元的形态特征。通过匈牙利3DHISTECH公司数字切片扫描系统测量尺测量神经元细胞直径,比较固定液对细胞收缩的影响。结果4%多聚甲醛、10%中性甲醛、Bouin’s溶液展现了良好的固定效果,固定后的大脑硬度适中,HE染色后的切片着色适中、色泽鲜艳、神经元各种细胞形态对比清晰,4%多聚甲醛因固定后切片无龟裂而更为理想。不同固定液固定后的海马体神经元存在细胞收缩方面的极显著差异(P<0.01),使用Carnoy、Davidson’s固定后的神经元各种细胞收缩最严重。结论4%多聚甲醛、10%中性甲醛、Bouin’s溶液是金黄地鼠海马体神经元较为理想的固定液,4%多聚甲醛溶液建议作为首选。

啮齿类动物Playfighting的行为学研究进展

Playfighting是一种常见的社会性互动形式,具有互惠性和合作性等特点。其贯穿于动物的整个生命周期,并且会通过影响动物的社交、认知和运动等进一步影响大脑的执行功能。啮齿类动物的playfighting行为因具有易识别、易量化等特点,而被广泛研究。本文主要以大鼠和金仓鼠为例,整理概述了近年来啮齿类动物playfighting行为的研究现状,包括行为模式及其相关影响因素,希望为今后进一步研究playfighting行为提供参考。

粉葛多糖改善金黄地鼠非酒精性脂肪肝及对肠道菌群的调节作用

目的研究粉葛多糖对高脂饮食诱导的金黄地鼠非酒精性脂肪肝(nonalcoholicfattyliverdisease,NAFLD)的改善作用及与肠道菌群的关系。方法金黄地鼠随机分为空白组、高脂模型组、粉葛多糖高剂量组(100 mg/kg)、粉葛多糖低剂量组(50 mg/kg)。15周后,测定肝脏质量、肝指数、血脂及脂多糖(lipopolysaccharide,LPS)水平,肝脏及结肠切片苏木素-伊红染色,结肠内容物16S rRNA测序。结果与高脂模型组相比,粉葛多糖显著降低了肝脏质量及肝指数,改善了总胆固醇、低密度脂蛋白胆固醇水平,甘油三酯及LPS水平显著降低,可改善肠道屏障损伤及肝脏脂肪变性;在肠道菌群门水平上,粉葛多糖能降低肠源性LPS主要来源菌门Proteobacteria的相对丰度至0.05%,在属水平上,粉葛多糖能促进与肥胖呈负相关的Parabacteroides及与肠道黏膜修复相关的Lachnospiraceae NK4A136 group富集。结论粉葛多糖可能通过调节肠道菌群改善高脂饮食诱导的金黄地鼠NAFLD。

柯萨奇病毒B组1型感染叙利亚金黄地鼠动物模型建立

目的建立叙利亚金黄地鼠CVB1(Coxsackievirus B1,CVB1)感染动物模型。方法取叙利亚金黄地鼠经鼻腔滴注方式呼吸道感染CVB1,感染剂量每只为10^(7.25)CCID_(50)。观察14 d体重、体温、精神状态、皮肤黏膜变化、行为、粪便状态、是否有神经症状等临床情况;每天采集咽拭子、鼻灌洗液以及粪便进行病毒载量检测,感染第7天取3只实施安乐死,采血进行病毒载量及生化检测;同时采集脑、心脏、肝等多个组织样品进行病毒载量、组织病理学和IHC检测。结果感染CVB1病毒的动物在14 d内均出现不同程度精神萎靡、体温下降,以及口唇部出现典型的红疹及疱疹等类似人类手足口病临床表现。咽拭子、鼻灌洗液、粪便以及血液中能检测到病毒;组织中检测到病毒载量并观察到病毒抗原,同时伴有炎症、增生、出血等病理改变;血清酶中肝功、心肌酶升高。结论CVB1病毒经滴鼻方式感染叙利亚金黄地鼠建立的感染模型,表现出心肌和肝等组织器官的病理损伤特征,可用于人类手足口病的研究。

金黄地鼠生物净化及其应用

金黄地鼠被用于研究人类相关疾病已有60多年,广泛应用于新型冠状病毒、代谢性疾病发病机制、疫苗和治疗性药物效果评价的研究中。WTO规定用于疫苗生产和检定的金黄地鼠必须达到无特定病原体(specific pathogen free,SPF)级,而目前国内使用的多为普通级。通过生物净化提升金黄地鼠种群微生物等级势在必行。本文概述了金黄地鼠在新型冠状病毒、代谢性疾病研究中的应用及相关生物净化技术工作进展。

高温致金黄地鼠神经管畸形中细胞凋亡的组织学观察

为研究细胞凋亡与高温致神经管畸形的关系，采用核固红－结晶紫染色方法和电镜技术，观察高温后胚胎发育变化。结果显示，高温后８ｈ胚胎发育迟缓，神经管延迟闭合或不闭合，胚胎各段尤其是头部的神经上皮和周围间充质的细胞凋亡比对照组增多，其超微结构改变为染色质浓缩、边聚，核膜皱缩，微绒毛消失并出现异常的胞质突起；１６ｈ后细胞凋亡明显增多，胞质内出现了大量空泡，凋亡小体增多；２４ｈ后细胞凋亡逐渐减少，凋亡小体被邻近的细胞吞噬，于７２ｈ后细胞凋亡恢复至对照组水平。结果表明，高温能促进神经上皮和周围间充质的细胞凋亡，使存活细胞数减少，结果导致了神经管延迟闭合或不闭合。

流行性出血热(EHF)地鼠肾细胞(GHKC)灭活疫苗的初步人体观察

用流行性出血热(EHF)病毒L99株(家鼠型)感染金黄地鼠肾细胞(GHKC),经福尔马林(0.025％)灭活制备EHF灭活疫苗(88-17批),经检定批准,肌肉(1ml)接种志愿者12人(IO人于0、7、28天,2人分别于0、7天及0、28天各一针),进行了安全性及抗体反应的初步人体观察。结果显示,此种疫苗对人体接种无明显不良反应。接种后,12名接种者IFA、ELI-SA及中和抗体(EFRNT)全部阳转,180天和360天后仍分别有10人血清中和抗体阳性。初步表明,此疫苗是安全的,可以有效诱导抗体产生,其中和抗体多数可持续一年以上。