姬松茸多糖抗应激作用的研究

为研究姬松茸多糖的抗应激作用,我们选择体重为18±2g的雄性昆明种小鼠,分成对照组、小剂量给药组、中剂量给药组和高剂量给药组。对照组皮下注射生理盐水0.15mL/只,各给药组分别皮下注射2%、4%和8%的姬松茸多糖溶液0.15mL/只,每日一次,共10d,各组分别进行常压耐缺氧试验、游泳试验、耐寒和耐高温试验。结果:在耐高温试验中,2%和4%多糖组小鼠的生存时间显著高于对照组;其它试验中,各给药组与对照组相比无显著差异。结论:一定浓度的多糖能显著延长小鼠耐高温的时间,但未显示出明显的耐低温、耐缺氧和抗疲劳的作用。     

全反式视黄酸对小鼠卵泡发育、繁殖性能和生殖激素水平的影响

本研究旨在探讨全反式视黄酸（ATRA）对昆明小鼠卵泡发育、繁殖性能和生殖激素水平的影响。试验选取7周龄雌性昆明小鼠24只,适应性饲养5～7 d后,随机分为4组,每组6个重复,每个重复1只,分别为对照组（灭菌蒸馏水）、低剂量组（0.1 mg/kg ATRA）、中剂量组（1.0 mg/kg ATRA）和高剂量组（10.0 mg/kg ATRA）,连续灌胃14 d。各组分别取6只昆明小鼠采样,测定血清雌激素（E2）、孕酮（P4）和促卵泡生成素（FSH）水平,同时分离卵巢并计算卵巢系数,制作卵巢组织石蜡切片,并进行卵泡计数。选择未发情的昆明小鼠64只,随机分为4组,每组16个重复,每个重复1只。剂量同上。连续灌胃ATRA 1个发情周期（5 d）。将发情小鼠各组取6只采样,测定血清激素水平,其余10只与雄性小鼠合笼,妊娠期间每周称量1次体重,分娩之后统计窝产仔数、出生窝重与出生个体重。结果表明：1）昆明小鼠连续灌胃ATRA14 d,与对照组相比,ATRA对小鼠的体重与卵巢系数均没有显著影响（P>0.05）。2）与对照组相比,高剂量组初级卵泡的数量显著提高（P<0.05）,而闭锁卵泡数...     

地菍总黄酮的急性毒性及降糖活性研究

本研究旨在探讨地菍总黄酮的急性毒性及对糖尿病小鼠的降血糖活性。试验以单次最大给药剂量（5.6 mg/g体重）和最大给药体积（40 μL/g体重）的地菍总黄酮混悬液对正常小鼠进行灌胃。24 h内给药2次后连续观察14 d,记录小鼠的存活情况及一般状态,给药14 d后采集小鼠血清并检测谷草转氨酶（AST）、谷丙转氨酶（ALT）活性及肌酐（Cre）、尿素氮（BUN）含量,计算小鼠心脏、肝脏、脾脏、肺脏、肾脏的质量系数。采用一次性腹腔注射0.160 mg/g体重链脲佐菌素（STZ）建立糖尿病小鼠模型,验证地菍总黄酮对糖尿病小鼠的保护作用。试验设空白组、模型组、二甲双胍组（0.6 mg/g体重）、地菍总黄酮高剂量、中剂量及低剂量组（1.2、0.8、0.53 mg/g体重）,连续给药21 d后,测定各组小鼠空腹血糖（FBG）、体重、采食量、饮水量及24 h尿蛋白含量。地菍总黄酮急性毒性试验结果显示,地菍总黄酮灌胃给药的日最大给药量为11.2 mg/g体重;给药后14 d,与正常组相比,给药组小鼠体重、各脏器质量系数、血清中AST、ALT活性及Cre、BUN含量无显著差异（P>0.05）。在验证地菍总黄酮降血糖活性试验中,与模型组相比,地菍总黄酮给药组小鼠FBG、饮水量、采食量显著或极显著降低（P<0.05;P<0.01）。上述结果证实地菍总黄酮安全性高,未引起试验小鼠明显的急性毒性反应,并可有效降低糖尿病小鼠血糖含量,缓解小鼠糖尿病症状。     

刺五加对糖尿病动物模型的降血糖影响初探

为了探讨长白山天然野生刺五加对实验性糖尿病小鼠血糖的影响,试验选用昆明种小鼠,禁食12h,腹腔注射四氧嘧啶,选择性破坏胰岛β细胞,造成小鼠实验性糖尿病模型。取40只糖尿病模型小鼠随机分为刺五加高、中、低剂量组和四氧嘧啶模型组,另取重量相近的正常10只昆明种小鼠作为空白对照组。刺五加高、中、低剂量组分别给予5.00,1.25,0.25g/kg的刺五加水煎液灌胃,四氧嘧啶模型组和空白对照组给予同体积的生理盐水。连续灌胃15d,测定其空腹血糖,观察模型小鼠血糖变化。结果表明,刺五加高、中剂量组的血糖值分别为（13.51&#177;1.42）mmol/L、（15.39&#177;0.79）mmol/L,与模型对照组（19.62&#177;1.28）mmol/L相比,极显著降低血糖水平（P＆lt;0.01）。低剂量组（17.39&#177;0.64）mmol/L与模型对照组相比,差异显著（P＆lt;0.05）。由此可见,长白山野生刺五加对实验性小鼠具有降血糖作用。     

青钱柳醇提取物对糖尿病小鼠降血糖作用的研究

采用四氧嘧啶选择性破坏昆明种小鼠的胰岛β细胞,造成实验性糖尿病模型小鼠共160只,随机分成5组,每组2个重复,设消渴丸组、四氧嘧啶组,青钱柳提取物高、中、低浓度组。尔后用青钱柳醇提取物给该小鼠灌胃,测定其空腹血糖浓度,观察小鼠血糖浓度和体重变化,最后进行糖耐量试验。结果表明:在灌胃青钱柳70%醇提取物2周和3周后,高、中浓度的青钱柳醇提取物组小鼠的血糖浓度明显低于糖尿病模型组小鼠的血糖(P<0 05);给药4周后,高、中浓度组和消渴丸组小鼠的血糖浓度明显低于糖尿病模型组的血糖浓度(P<0 05);给药5周和6周后,低浓度组和消渴丸组小鼠的血糖浓度明显低于糖尿病模型组的血糖浓度(P<0 05),而高、中浓度组小鼠的血糖浓度与糖尿病模型组的血糖浓度相比,差异极显著(P<0 01);在第4周和第5周时,低浓度组小鼠的体重明显低于空白对照组小鼠的体重(P<0 05);同时,青钱柳对试验性小鼠的糖耐量具有显著的增强作用。     

两色金鸡菊提取物对运动小鼠抗疲劳和耐缺氧作用的研究

为研究两色金鸡菊提取物对小鼠的抗疲劳和耐缺氧作用,选择48只小鼠随机分为4组,即对照组,低、中、高剂量两色金鸡菊提取物组(每日5、10、20g/kg体重)。各组小鼠分别灌胃(每日0.20mL/10g)给予不同剂量的两色金鸡菊提取物,连续灌胃21d后,观察不同浓度的两色金鸡菊提取物对小鼠负重游泳时间及运动后小鼠血清尿素氮、血乳酸、肝糖原含量和小鼠常压耐缺氧存活时间、断头后呼吸维持时间的影响。结果表明,两色金鸡菊提取物能延长小鼠负重游泳时间,降低运动小鼠血清尿素氮、血乳酸含量,增加运动小鼠肝糖原含量,明显延长小鼠常压耐缺氧存活时间及断头后呼吸维持时间。结果提示,一定剂量的两色金鸡菊提取物具有抗疲劳作用和提高耐缺氧能力作用。     

链脲佐菌素诱导小鼠Ⅱ型糖尿病模型的研究

通过注射链脲佐菌素(STZ)诱导建立与人类Ⅱ型糖尿病(NIDDM)相似的昆明鼠和C57鼠模型,比较两种鼠建模剂量和成模率的差异。将昆明鼠和C57小鼠随机分为正常对照组(A)及低、中、高剂量(每天50、70、90 mg/kg)用药组(B)(n=10)。正常对照组(A)饲喂普通饲料,用药组(B)饲喂高脂高糖饲料;第4周开始,A组腹腔注射柠檬酸缓冲液,B组腹腔注射STZ,连续4 d。测定给药前和给药后3、7、15 d空腹血糖和体重,观察小鼠饮食、饮水和排尿情况。给药前空腹血糖A、B组间无显著性差异(P0.05);昆明鼠用药3 d后中、高剂量组均升高并达到建模标准,C57鼠用药7 d后中、高剂量组达到建模标准。两种小鼠用药3 d后各组体重均减低,并与对照组间有极显著差异(P0.01)。C57鼠,STZ注射剂量越高,体重减轻幅度越大;并且自造模成功后,各用药组体重均出现逐日降低的趋势。诱导建立NIDDM模型的适宜STZ剂量昆明鼠为每天50 mg/kg和70 mg/kg,并以后者为佳;C57鼠为每天70 mg/kg。     

可溶性环氧化物水解酶抑制剂的降血糖功效研究

为探究可溶性环氧化物水解酶抑制剂（soluble epoxide hydrolase inhibitors,sEHI）的降血糖功效,试验以高脂饲料与链脲佐菌素（streptozotocin,STZ）联合诱导的Ⅱ型糖尿病小鼠为研究对象,将C57BL/6J小鼠随机分为：正常对照组、糖尿病模型组和sEHI组,sEHI组饲喂高脂饲料,每日灌胃sEHI （t-AUCB）1 mg/kg,连续灌胃4周;糖尿病模型组饲喂高脂饲料,每日灌胃同等计量的生理盐水;正常对照组饲喂普通饲料,每日灌胃同等体积的生理盐水。期间各组小鼠均自由采食及饮水,记录小鼠体重、血糖并进行口服葡萄糖耐量试验。试验结束后,测定血清血脂指标、肝脏过氧化指标并对小鼠胰岛组织进行病理学分析。结果显示,与糖尿病模型组相比,采用sEHI干预后糖尿病小鼠的空腹血糖显著降低（P<0.05）,而葡萄糖耐量水平升高;小鼠血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平明显降低,其中TC、TG水平与糖尿病模型组相比差异显著（P<0.05）,而高密度脂蛋白与胆固醇比值（HDL/TC）水平则显著升高（P<0.05）;与糖尿病模型组相比,sEHI干预组小鼠肝脏的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性显著提高（P<0.05）,丙二醛（MDA）活性显著降低（P<0.05）;小鼠的胰岛组织切片分析结果表明,sEHI对小鼠胰岛组织有明显的修复作用。综上所述,sEHI具有降血糖、减轻自由基损伤、抑制脂质过氧化、修复受损胰岛组织的作用。     

党参多糖口服液抗应激及抗炎作用的研究

为研究党参多糖口服液的抗应激与抗炎作用,给小鼠灌服不同剂量（每kg体重灌服9、7、5 g生药）的党参多糖口服液后,通过测定小鼠负重游泳时间、常压耐缺氧时间来评价其应激性作用;观察党参多糖口服液对小鼠耳廓二甲苯致炎的影响,考察其抗炎作用.结果显示,党参多糖口服液能显著（P＜0.01）延长小鼠的游泳时间和常压缺氧条件下的存活时间,对二甲苯所致小鼠耳廓炎症具有不同程度的抑制作用.因此,党参多糖口服液具有抗应激、抗炎作用,该试验可为党参多糖口服液的临床应用提供参考.     

螺旋藻的急性和亚慢性毒性试验

[目的]旨在评价螺旋藻的毒性,从而为临床安全用药提供理论依据。[方法]以昆明小鼠为研究对象,进行急性和亚慢性毒性试验。在急性毒性试验中,采用不同浓度的螺旋藻水溶液进行小鼠灌胃来测定螺旋藻的半数致死量和最大耐受量;在亚慢性毒性试验中,小鼠以（10．0、5．0、2．5g／kg）不同剂量连续饲喂28d,在给药第28天观察小鼠的临床体征、体重、饲料利用率、白细胞总数、血液生化指标和病理组织学变化。[结果]急性毒性试验各剂量组小鼠均无死亡,无法测出LD50最大耐受量为10g／kg。亚慢性毒性试验中用药组小鼠的临床体征、体重、饲料利用率、白细胞计数、血液生化指标与空白对照组小鼠相比,无显著差异（P〉0．05）。组织病理学观察,实质器官无异常病变。[结论]螺旋藻实际无毒,安全性好。     

柞蚕全蚕粉对诱导型小鼠糖尿病的预防作用

饲喂添加不同剂量柞蚕全蚕粉的全价配合饲料4周后,通过尾静脉注射四氧嘧啶建立糖尿病小鼠模型,观察柞蚕全蚕粉对糖尿病小鼠血糖、脂代谢[甘油三酯(TG),总胆固醇(TC),高密度脂蛋白(HDL-C),低密度脂蛋白(LDL-C)]的影响。结果表明:添食中、高剂量柞蚕全蚕粉可显著降低糖尿病小鼠血糖,分别比阳性对照组降低了31.3%、42.5%(p<0.01)。各剂量组TG、TC、LDL-C较阳性对照组均有不同程度降低,其中:高剂量组LDL-C与阴性对照组无差异(p>0.05);HDL-C较阳性对照组均有升高,中、高剂量组与阳性对照组有显著性差异(p<0.05)。柞蚕全蚕粉能够降低糖尿病小鼠的血糖,且调节糖尿病小鼠的脂代谢和降低TG,TC。     

Silk fibroin hydrolysate exerts an anti-diabetic effect by increasing pancreatic β cell mass in C57BL/KsJ-db/db mice

Components of silk including silk fibroin have long been used as anti-diabetic remedies in oriental medicine. However, detailed mechanisms underlying these anti-diabetic effects remain unclear. In this study, we examined the anti-diabetic activity of silk fibroin hydrolysate (SFH) in C57BL/KsJ-db/db (db/db) mice, a well-known animal model of non-insulin dependent diabetes mellitus. When the db/db mice were administered SFH in drinking water for 6 weeks, hyperglycemia in the animals gradually disappeared and the level of glycosylated hemoglobin decreased, indicating that SFH plays important role in reducing the symptoms of diabetes. In addition, SFH-treated db/db mice exhibited improved glucose tolerance with increased plasma insulin levels. Immunohistochemical and morphological analyses showed that SFH up-regulated insulin production by increasing pancreatic β cell mass in the mice. In summary, our results suggest that SFH exerts anti-diabetic effects by increasing pancreatic β cell mass in a non-insulin dependent diabetes mellitus mouse model.     

茧壳水煎剂对四氧嘧啶糖尿病模型小鼠的降血糖作用

用不同剂量的茧壳水煎剂分别对正常小鼠和四氧嘧啶糖尿病模型小鼠进行了降血糖作用研究。结果显示 :干茧壳剂量为 1 6、3 2g/kg·d的茧壳水煎剂对正常小鼠连续灌胃 2 0d ,其血糖水平没有明显变化 ;用干茧壳剂量为 1 6g/kg·d的茧壳水煎剂对四氧嘧啶糖尿病模型小鼠连续灌胃 2 0d ,或用干茧壳剂量为 3 2g/kg·d的茧壳水煎剂对四氧嘧啶糖尿病模型小鼠连续灌胃 10d ,其血糖没有显著降低 ;而干茧壳剂量为 3 2g/kg·d的茧壳水煎剂对四氧嘧啶糖尿病模型小鼠连续灌胃 14、2 0d ,有显著的降血糖作用 ,但是若不继续灌胃给药 ,则 7d后 ,这种降血糖作用又丧失。该研究结果为利用蚕茧治疗糖尿病提供了药理学方面的依据     

山茱萸不同提取物降血糖作用研究

以正常小鼠和四氧嘧啶糖尿病小鼠为动物模型,分别对山茱萸乙醚提取物、乙酸乙酯提取物和乙醇提取物的降血糖作用进行研究。结果表明,山茱萸3种提取物组与模型组比较,均可显著降低四氧嘧啶糖尿病小鼠血糖水平(P0.01)。山茱萸3种提取物组间比较,乙酸乙酯提取物组的降血糖作用最明显(P0.05)。正常小鼠对照实验表明,山茱萸3种提取物对正常小鼠的血糖无明显影响(P0.05)。本试验筛选出山茱萸乙酸乙酯提取物为山茱萸的降血糖活性成分。     

Segmentation of the Pathophysiological Stages of Diabetic Changes in the db/db Mouse

The db/db mouse is one of the diabetes mellitus animal models and if the pathophysiological stages of diabetic changes in the mouse model could simulate the stages in human diabetes, the db/db mouse could be used to better evaluate drug candidates. Blood insulin, HbA1c levels and morphological features of pancreatic islets in db/db mice were evaluated to determine the pathophysiological stage. At 6 weeks of age, db/db mice showed the highest level of plasma insulin and lowest level of HbA1c, and histopathological examination revealed enlarged islets with a circular shape and hypertrophic islet cells. By 9 and 12 weeks of age, the plasma insulin levels had decreased to mid levels and HbA1c had increased to mid to high levels; histopathological examination at this time revealed two types of islets coexisting, enlarged circular islets and small irregular-shaped islets. By 15 and 22 weeks of age, plasma insulin had decreased further to low levels and HbA1c was at its highest level; the histopathological examination at this time revealed an increase in irregular-shaped and small islets. Based on blood insulin levels, HbA1c levels and histopathology findings in the db/db mice in this study, the clinical staging of diabetic changes were recognized. The pathophysiological stages of diabetes mellitus in this animal model were similar to the stages in humans.     

姬松茸多糖降血糖、降血脂作用的研究

为研究姬松茸多糖降血糖和降血脂的作用，我们建立了四氧嘧啶性糖尿病模型和急性高血脂模型，观察不同浓度的姬松茸多糖对高血糖和高血脂小鼠的治疗和预防作用结果：4％和8％多糖组小鼠的血糖含量显著低于糖尿病模型；各多糖组小鼠血清的甘油三酯(TG)和胆固醇(TC)水平与高血脂模型相比，差异不显著这说明一定浓度的姬松茸多糖具有降血糖作用，但未显示出降血脂作用     

Sex difference feeding behaviour of NOD SCID mice in a pharmacological model of type 1 diabetes

This study aimed to assess the sex differences in the feeding behaviour of non-obese diabetic severe combined immunodeficient (NOD SCID) mice in a pharmacological model of type 1 diabetes mellitus (T1Dm). In our study, we chose NOD SCID mice of both sexes and assessed their feeding behaviour, body weight, body fat and water content under identical experimental conditions and diets. After 1 month of diabetes mellitus in mice in the experimental group, males and females did not show any increase in body weight, and they weighed significantly less than the control group. However, compared with the control group, in females with a background of T1Dm, there was a significant decrease in body fat. The amount of water consumed in the experimental groups was higher than that in the control groups. The amount of food consumed by males increased when they increased their water consumption, whereas food consumption in females decreased significantly with an increase in water consumption. Thus, we discovered sex differences in the feeding behaviour, body weight and body fat and water content in the pharmacological model of T1Dm after 1 month in NOD SCID mice.     

2株桑树内生菌发酵产物的降血糖作用

通过体外α-葡萄糖苷酶抑制试验和糖尿病模型小鼠动物试验,检验桑树内生菌菌株Stenotrophomonas maltophilia Y1和Micrococcus luteus Y2发酵产物的降血糖作用。结果表明,Y1和Y2菌株发酵液提取物对α-葡萄糖苷酶均具有显著的体外抑制作用,并呈现一定的剂量依赖性,半数抑制浓度(IC50)分别为2 307.56 mg/L和111.58 mg/L,在试验最大剂量下的抑制率分别达到59.17%和69.21%,均高于对照药物拜糖平(抑制率为53.06%)。动物试验表明,饲喂Y1菌株发酵液浓缩产物的糖尿病模型小鼠的空腹血糖(FBG)值和餐后血糖(PBG)值均低于模型组,分别存在显著和极显著差异,而对正常小鼠的血糖无明显影响,也未表现出毒副作用;调查饲喂发酵产物后糖尿病模型小鼠的体质量、进食量、饮水量、排尿量等指标,均得到明显改善。试验结果显示,2株桑树内生菌菌株的发酵液提取物均表现出与1-脱氧野尻霉素(DNJ)相同的体外抑制α-葡萄糖苷酶活性的作用,Y1菌株发酵产物表现出与DNJ相同的降低糖尿病模型小鼠血糖及改善糖尿病症状的作用特点。     

Erythrocyte-replaced mouse model for Haemoparasite studies: comparison of NOD/shi-scid and C.B-17/Jcl-scid mouse upon acceptability of human erythrocytes

The erythrocyte-exchanged chimera mouse model has become to be a significant tool for studying animal and human (hu) protozoan haemoparasites, though the usefulness of this model varies depending primarily on the acceptability of xenogeneic red blood cells (RBC). To find a superior recipient in comparison with C.B-17/Jcl mouse with severe combined immuno-deficiency (scid) mutation, we examined in this report the non-obese diabetes (NOD)/shi-scid mouse, a recently available strain of SCID. When 2.5 x 10(8) of fluorescent dye-labeled hu-RBCs were transfused, C.B-17scid mouse eliminated them logarithmically by a simple linear regression, while NOD-scid mouse eradicated hu-RBCs by a unique two-step fashion, i.e., a potent but only briefly functioning RBC eradication followed by a weak steadily functioning step. The means of regression line constance +/- their standard deviations (SD) of 205 C.B-17scid and of 213 NOD-scid mice for their short- and long-lasting steps were -0.73 +/- 0.63, -0.53 +/- 0.25 and -0.16 +/- 0.10, respectively. Hu-RBC half-lives determined from these means of C.B-17scid mice and of NOD-scid mice for the short- and long-living steps were 3.6, 4.9 and 16.3 hr, respectively. Higher hu-RBC acceptability of NOD-scid mouse, especially at their long-lasting step, was also demonstrated under at an activated state of mouse innate immunity. Treatment with 1.0 mg heat-killed Candida cells caused an acceleration of hu-RBC elimination in both mouse strains but the magnitudes for the short- and long-living steps of NOD-scid mice evaluated by "stimulation index" were only 1/2.6 and 1/7.6 of C.B-17scid mice, respectively.     

Insulin-like Growth Factor 1 mRNA Expression in the Uterus of Streptozotocin-treated Diabetic Mice

Reproductive functions decline with the onset of diabetes in female mice. Diabetic mice have smaller uteri with an underdeveloped endometrium, suggesting diminished estrogen-induced growth. We aimed to clarify the changes in the estrous cycle and in insulin-like growth factor 1 (IGF1) expression in the uteri of streptozotocin (STZ)-treated diabetic mice, because IGF1 is one of the main growth factors involved in estrogen-induced uterine growth. ICR female mice were intraperitoneally administered STZ (10 mg/100 g BW), and blood glucose levels were determined. Mice with blood glucose levels > 200 mg/dl were classified as diabetic mice. The onset of diabetes was associated with acyclic estrous cycles. Diabetes was also induced with STZ in ovariectomized mice. Uterine Igf1 mRNA levels were reduced in ovariectomized STZ-treated diabetic mice. Estrogen is known to stimulate Igf1 mRNA expression in the uterus, but estrogen action was abolished in the uteri of STZ-treated diabetic mice. mRNA expressions of estrogen receptor α (ERα) and steroid hormone receptor coactivators (SRC-1/Ncoa1, SRC-2/Ncoa2, SRC-3/Ncoa3 and CBP/p300/Crebbp) were reduced in the uteri of ovariectomized STZ-treated diabetic mice. The present study demonstrates that diabetes induces a decline in female reproductive functions in mice. Igf1 expression in ovariectomized diabetic female mice was decreased, and decreased responsiveness to estrogen in the uteri of diabetic mice is probably associated with a reduction in ERα and steroid receptor coactivator mRNA expression.