Antihyperglycemic Activity of Herb Extracts on Streptozotocin-Induced Diabetic Rats

We investigated the effects of herb extracts, Rhus verniciflua, Agrimonia pilosa, Sophora japonica, and Paeonia suffruticosa, on the lowering of blood glucose levels and thiobarbituric acid reactive substances (TBARS) in streptozotocin (STZ)-induced diabetic rats. After 4 weeks, oral administration of Rhus verniciflua extract (50 mg/kg) exhibited a significant decrease in blood glucose levels in diabetic rats (P<0.05). Blood TBARS concentrations, the products of glucose oxidation in blood, were also lowered by Rhus verniciflua extract supplementation. In addition, Sophora japonica and Paeonia suffruticosa extracts significantly reduced TBARS levels versus diabetic controls. Serum concentrations of liver-function marker enzymes, GOT and GPT, were also restored by Rhus verniciflua (50 mg/kg) supplementation in diabetic rats.     

cDNA RDA在类似普通2型糖尿病大鼠肾脏组织基因差异表达筛查中的应用

应用代表性差异分析 (cDNARDA)技术 ,对类似普通 2型糖尿病大鼠肾脏组织基因差异表达进行筛查 ,初步探讨类似普通 2型糖尿病大鼠肾脏损害发病的分子机制 .首先以类似普通 2型糖尿病大鼠肾脏组织作为实验组 (Tester) ,正常大鼠肾脏作为对照组或驱动组 (Driver)通过cDNARDA进行基因差异表达筛查 ;最终的差异产物亚克隆到Puc 18载体 ,测序及并进行生物信息学分析 ;半定量RT PCR对筛查到新的基因进行初步的鉴定 .结果发现 9个新ESTs ,2个新基因 .这 2个新基因分别与人及小鼠的丝氨酸蛋白酶抑制因子F ,及真核细胞转录启动因子 3亚单位 5 (EIF 3epsilon)基因有高度的相似性 (>90 % )并在类似普通 2型糖尿病大鼠肾脏组织表达上调 .推测 2个新基因分别是大鼠的丝氨酸蛋白酶抑制因子F及真核细胞转录启动因子 3亚单位 5 .两个新基因在类似普通 2型糖尿病大鼠肾脏组织表达上调 ,可能与类似普通 2型糖尿病大鼠肾脏损害相关 .同时 ,对新基因RS91进行了全长cDNA克隆     

芦笋老茎澄清汁对链脲佐菌素致糖尿病大鼠降糖作用的研究

本文评价了芦笋老茎澄清汁(CAJ)的降血糖作用,并对其降血糖机制进行了初步探讨。腹腔注射STZ制备类似1型糖尿病大鼠模型,以0.6,1.2和2.0 g/kg体重剂量的CAJ连续灌胃21 d,监测血糖,测定糖化血清蛋白、血清胰岛素、肝糖原、脂代谢及抗氧化系统部分相关指标。结果显示,CAJ可明显降低糖尿病大鼠血清中葡萄糖、糖化血清蛋白、总胆固醇和MDA含量,并显著提高受试模型鼠的血清胰岛素水平、肝糖原含量、血清SOD活性、肝脏SOD、GSH-Px和CAT的活性。上述结果表明CAJ可明显降低糖尿病大鼠的血糖水平,刺激胰岛素分泌,调节血脂,增强抗氧化能力。     

基因表达系列分析技术的新进展

作为新近建立的研究基因表达的有效工具 ,基因表达系列分析 (SAGE)技术能同时对大量的转录物进行定性和定量分析。它不仅可以显示低丰度的转录物 ,提供基因组表达的完整信息 ,而且可以通过不同状态下基因表达图谱的比较 ,深入了解基因表达的时空性和有序性 ,从而寻找和发现新基因。本文介绍了SAGE的工作原理和方法 ,并着重对其最新的应用与研究进展进行了综述。     

用cDNA表达阵列分析遗传性癫痫易感大鼠海马和大脑皮质的基因表达

采用Atlas^TM Rat cDNA Expression Array建立遗传性癫痫易感性P77PMC大鼠和正常对照Wistar大鼠的海马与大脑皮质基因表达谱,用Eagle EyeⅡStill Video System(Stratagene)图象分析仪分析两者基因表达谱差异.结果发现海马和大脑皮质中各有15个差异表达基因.海马组织中,12个基因在P77PMC大鼠中高表达而在正常对照Wistar大鼠中低表达,3个基因在正常对照Wistar大鼠中高表达,而在P77PMC大鼠中低表达;大脑皮质中,13个基因在P77PMC大鼠中高表达,而在正常对照Wistar大鼠中低表达,2个基因在正常对照Wistar大鼠中高表达,而在P77PMC大鼠中低表达. 结果说明,P77PMC大鼠与正常对照Wistar大鼠海马和大脑皮质存在多个差异表达基因,这些差异表达基因可能在癫痫的发生中扮演了重要角色.     

Effect of Antipsychotic Drugs on the Gene Expression of NMDA Receptor Subunits in Rats

It has been hypothesized that glutamatergic neurons play an important role in clinical manifestations of schizophrenia and that the therapeutic effect of antipsychotic drugs is related to glutamatergic neurotransmission. To elucidate the effect of antipsychotic drugs on glutamatergic transmission, we examined gene expressions of NMDA receptor subunits Rl, R2A, R2B and R2C in the whole brains of rats after acute and chronic administrations of haloperidol and sulphide, using the Northern blot technique. The levels of NMDAR2B mRNAs decreased after the acute administration of haloperidol, but showed no change after the chronic administration. The levels of NMDAR2A and R2B mRNAs decreased after the acute administration of sulpiride, whereas the levels of R2A and R2B increased following the chronic administration. Neither haloperidol nor sulpiride influenced NMDAR1 mRNA levels. These data support differential expression of NMDA receptor subunits in rats upon treatment with haloperidol and sulpiride. The results imply that NMDAR2 subunits may be crucial in the regulation and modification of antipsychotic drugs.     

肢体缺血-再灌注大鼠脑组织iNOS基因表达的半定量检测

目的检测大鼠肢体缺血-再灌注后脑组织iNOS基因表达的变化.方法SD大鼠,随机分为肢体缺血-再灌注(I-R)组、肢体单纯缺血(I)组及正常对照(N)组,通过夹闭腹主动脉末端4?h,或/和开放2～24?h,复制I、I-R组动物模型,半定量RT-PCR方法检测脑组织iNOSmRNA表达的变化,免疫组化染色法观测脑组织内iNOS及过氧亚硝基阴离子(ONOO-)的硝基化产物硝基酪氨酸(NT)的生成与分布.结果N组脑组织iNOSmRNA未检出,I组及I-R组脑组织iNOSmRNA均有表达,再灌注2?h,iNOSmRNA表达量显著升高(P<0.01,vsN组),再灌注6?h达到高峰,随后下降,24?h仍有少量表达;I及I-R组脑组织均有iNOS阳性细胞,I-R组见于大脑皮层各区、海马、尾状核,I组仅见于皮层后肢区及尾状核.I-R组脑组织可见弥散分布的NT阳性神经元,I组偶见NT阳性神经元.结论大鼠肢体缺血-再灌后脑组织iNOS基因表达显著增强,且有时相变化特征.     

姜黄素对糖尿病大鼠疼痛过敏的影响

目的：神经病理性痛是糖尿病最常见的并发症之一,本课题旨在探讨姜黄素对糖尿病大鼠痛觉过敏的影响及其分子机制。方法：30只雄性SD大鼠随机分为对照组、糖尿病组和姜黄素治疗纽,模型纽和姜黄素治疗组利用腹腔注射链脲佐菌素（Streptozotocin,STZ）制备大鼠糖尿病模型,定期检测大鼠血糖、饮食、体重等变化,治疗组于STZ注射2wk后定期灌服姜黄素,分别在2wk和4wk后检测各组大鼠热痛敏和机械痛敏反应,在第4wk利用ELISA分别检测各组大鼠脊髓背角TNF-α表达变化。结果：STZ注射组大鼠2周后出现血糖〉14mol／L,并且该模型具有高血糖、体重增长缓慢、多饮多食多尿的特点,符合Ⅰ型糖尿病特征,痛行为测试结果显示糖尿病大鼠出现痛觉过敏,经过给予姜黄素灌服治疗后,痛觉过敏有所减轻,ELISA分析结果表明糖尿病大鼠脊髓背角TNF-α表达升高,经过姜黄素治疗后TNF-α表达有所下降。结论：成功制备STZ-型糖尿病大鼠模型,经过姜黄素治疗可以减轻糖尿病引起的疼痛过敏,姜黄素对糖尿病疼痛的治疗作用可能是通过降低大鼠脊髓背角TNF-α表达实现的。     

The Effect of Glutathione Treatment on the Biochemical and Immunohistochemical Profile in Streptozotocin-Induced Diabetic Rats

This study investigated the possible role of glutathione (GSH) in diabetic complications and its biochemical safety in experimental diabetic rats. Serum biochemical parameters and the histology of the pancreas were investigated. Seven rats were separated as controls. To create the diabetes in rats, 45 mg/kg single-dose streptozotocin (STZ) was administered i.p. The treatment was continued for 1 month. STZ was administered to the diabetes + GSH group, then reduced GSH, dissolved in isotonic salt solution (200 mg/kg), was applied i.p. two times a week. The GSH group received i.p. GSH. Serum biochemical parameters were determined by autoanalyzer. Immunohistochemical procedures were used to determine the percentage of the insulin-immunoreactive β-cell area in the islets of Langerhans. The biochemical parameters changed to different degrees or did not change. Pancreatic cells of the control and GSH groups were healthy, but in the diabetic and GSH-treated diabetic groups we found damage in different numbers. The results from these analyses show that GSH supplementation can exert beneficial effects on pancreatic cells in STZ-induced diabetic rats and can safely be used for therapy in and protection from diabetes and complications of diabetes.     

FXR在糖尿病大鼠回肠的表达水平及意义

目的:探索法尼酯衍生物受体(farnesoid X receptor,FXR)在链脲佐菌素(Streptozotocin,STZ)诱导的1型糖尿病(diabetes mellitus,DM)大鼠模型回肠组织中的表达水平及意义。方法:将大鼠随机分为正常对照组(NC组)和DM模型组(DM组)。腹腔注射STZ建立DM大鼠模型,NC组予无水乙醇生理盐水溶液腹腔注射。通过实时荧光定量PCR检测FXR在回肠组织m RNA表达水平。结果:(1)DM组FXR m RNA表达量减少、糖化血红蛋白升高、平均血糖升高、体重下降与NC组之间的差异有统计意义(P0.05);(2)FXR m RNA表达量pearson相关分析:DM组平均血糖、糖化血红蛋白、最终体重与最高体重相比下降的程度、最终体重与造模时体重相比下降的程度与FXR m RNA表达量呈负相关;(3)FXR m RNA表达量多元线性回归分析:DM组平均血糖、最终体重与最高体重相比下降的程度、糖化血红蛋白对FXR m RNA表达量的影响大(P0.05),而NC组各个指标对FXR m RNA表达量无影响(P0.05)。结论:FXR表达异常与糖尿病的发病和糖尿病患者的体重下降相关。     

离心机训练对大鼠脑和心脏组织基因表达的影响

 分析离心机训练对大鼠脑和心脏组织基因表达的影响 ,并从中筛选正加速度 (forwardaccel eration ,+Gz)高耐力相关基因 .雄性SD大鼠在动物离心机上训练 ,刺激G值从 + 7Gz～ + 12Gz ,每天增加 + 0 5Gz ,第 12d重复 + 12Gz刺激 ,第 13d在离心机上通过测定动物的 +Gz耐力筛选出高耐力动物 ,立即断头处死 ,取全脑和心脏组织 ,分离其mRNA .将此mRNA与未处理动物相应组织来源的mRNA进行抑制性消减杂交 (SSH) ,获得的相关EST(expressionsequencetag ,EST)进行序列测定 ,并经BLAST进行计算机分析 .结果获得 88条与离心机训练相关的EST ,其中 4 4条为已知基因的部分序列 ,4 4条为未知基因的部分序列 .提示离心机训练对大鼠脑和心脏组织基因表达有影响 ;这些相关基因可能与 +Gz高耐力的产生有关     

大鼠脑组织中胆囊收缩素基因表达与发育的关系

研究CCK基因在不同日龄大鼠脑中转录水平上的表达。取出生后不同日龄Wistar大鼠脑组织,提取总RNA,甲醛凝胶电泳,Northern印迹与α-32P标记CCKcDNA的探针杂交,放射自显影后,经激光扫描测定自显影图中斑点光密度,以估量CCKmRNA表达的相对水平。结果表明,刚出生的大鼠脑中CCK的mRNA含量甚低,随着鼠龄增长,浓度增高,20日龄时CCKmRNA浓度急剧升高,40日龄CCKmRNA的水平稍降低。CCK基因在转录水平的表达与个体发育有关。 Abstract：In this paper the clone was used as probe to study its expression for revealing the relationship between the level of CCK mRNA and the brain development.Total RNA from Wistar rats of various stages of development was isolated by acid guanidinium-thiocyanate phenol-chloroform extraction,followed by formaldehyde gel-electrophoresis.Northern blot,hybridization with a32P-labeled CCK cDNA probe,autoradiography and quantitation were performed by the laser density scanning.It was concluded from the results that the quantites of CCK mRNA in rat brain increased during development.From those mentioned above,it can be said that brain CCK mRNA may serve as a marker for the brain development.     

Effect of cerebrocrast on the lymphocyte blast transformation activity in normal and streptozotocin‐induced diabetic rats

Both IDDM and NIDDM are characterized by deviations in peripheral T and B lymphocyte count, T_helper:T_suppressor ratio, as well as by impaired T_suppressor function. These abnormalities may promote insulin antibody and other antibody production, contributing to overt diabetes mellitus development in early stage of the disease. In the present study we explored the effects of cerebrocrast (1,4‐dihydropyridine derivative) administration on Con A‐ and IL‐2‐stimulated tissue lymphocyte blast transformation activity and on the thymus and lymph node mass in normal and streptozotocin (STZ)‐induced diabetic rats. It was established that cerebrocrast, administered four times at the doses of 0·05 and 0·5 mg kg⁻¹, has long‐term (up to 14 days) effects on the immune system and protects against the toxic effect of STZ in STZ‐induced diabetic rats, preventing thymus and lymph node mass loss. We conclude that cerebrocrast administration leads to the increase in number and activity of T_helper and T_suppressor lymphocytes. Glycolysis and DNA synthesis in these cells is augmented under the influence of cerebrocrast administration. We propose that the increase in lymphocyte suppressive activity caused by cerebrocrast administration may prevent the development of IDDM and NIDDM in patients with pre‐diabetes, but in patients with early and overt diabetes mellitus the drug administration may prevent the overexpression of insulin antibodies and other antibodies. The effect of cerebrocrast on the de novo production of insulin and IL‐2 receptors may be beneficial for IDDM and NIDDM patients. Copyright © 1999 John Wiley & Sons, Ltd.     

亚硒酸钠对糖尿病肾病大鼠肾脏Nephrin表达的影响与意义

探讨亚硒酸钠对糖尿病肾病大鼠肾脏Nephrin表达的影响及二者间的关系,从而研究亚硒酸钠和Nephrin在糖尿病肾病中的作用机制.通过链脲佐菌素法及给予高脂饮食诱导模拟大鼠糖尿病肾病模型,实验设空白对照组、糖尿病肾病对照组、亚硒酸钠干预组,亚硒酸钠干预组每日给予亚硒酸钠溶液灌胃,其它组给予等量生理盐水灌胃.灌胃10周后处死大鼠,取血、尿标本测相关生化指标.取肾脏组织戊二醛固定制作切片电镜下观察超微结构改变,取肾脏组织多聚甲醛固定制石蜡切片光镜下观察病理改变和免疫组化定位蛋白表达.取肾脏组织RT-PCR检测Nephrin的mRNA表达、Western Blotting检测nephrin的蛋白表达,分析各组数据的统计差异.结果发现亚硒酸钠干预组大鼠基本状况和生化指标较糖尿病肾病对照组明显改善,光镜和电镜下观察病理改变和超微结构病变较糖尿病肾病对照组明显减轻.免疫组化nephrin蛋白表达着色糖尿病肾病对照组较空白对照组减少,亚硒酸钠干预组较糖尿病肾病对照组着色明显增多.Nephrin mRNA和蛋白表达糖尿病肾病对照组较空白对照组明显降低,而亚硒酸钠干预组较糖尿病肾病对照组升高,但低于空白对照组,差异均有统计学意义（P〈0．05）．亚硒酸钠明显促进肾脏Nephrin表达,改善了糖尿病肾病,表明亚硒酸钠和Nephrin在防治和延缓糖尿病肾病的发生发展中可能起重要作用．     

胰岛素信号通路相关因子在2型糖尿病合并骨质疏松大鼠肝组织的表达

通过高糖高脂饲料联合小剂量链脲佐菌素和去卵巢手术制备2型糖尿病合并骨质疏松大鼠模型,探讨2型糖尿病合并骨质疏松大鼠肝组织胰岛素信号通路相关因子的表达及意义。结果表明:随着时间延长,2型糖尿病合并骨质疏松组(DOVX组)肝组织IGF-1、IRS-1较其他组mRNA及蛋白表达减少,单纯去卵巢组(NOVX组)IGF-1、IRS-1 mRNA及蛋白表达较假手术对照组(NS组)降低;糖尿病组(DS组)IRS-2较NS组mRNA及蛋白表达下降,但NOVX组与NS组IRS-2 mRNA及蛋白表达比较无明显差别。以上结果表明,2型糖尿病合并骨质疏松的发生可能与肝脏胰岛素信号通路受抑制有关。     

Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive 56MnO2 Particles at Low Doses

We have studied the biological effects of the internal exposure to radioactive manganese-56 dioxide (⁵⁶MnO₂), the major radioisotope dust found in soil after atomic bomb explosions. Our previous study of blood chemistry indicated a possible adverse effect of ⁵⁶MnO₂ on the liver. In the present study, we further examined the effects on the liver by determining changes in hepatic gene expressions. Male Wistar rats were exposed to ⁵⁶MnO₂ particles (three groups with the whole-body doses of 41, 90, and 100 mGy), stable MnO₂ particles, or external ⁶⁰Co γ-rays (2 Gy), and were examined together with the non-treated control group on postexposure day 3 and day 61. No histopathological changes were observed in the liver. The mRNA expression of a p53-related gene, the cyclin-dependent kinase inhibitor 1A, increased in ⁵⁶MnO₂ as well as in γ-ray irradiated groups on postexposure day 3 and day 61. The expression of a stress-responsive gene, nuclear factor κB, was also increased by ⁵⁶MnO₂ and γ-rays on postexposure day 3. However, the expression of cytokine genes (interleukin-6 or chemokine ligand 2) or fibrosis-related TGF-β/Smad genes (Tgfb1, Smad3, or Smad4) was not altered by the exposure. Our data demonstrated that the internal exposure to ⁵⁶MnO₂ particles at less than 0.1 Gy significantly affected the short-term gene expressions in the liver in a similar manner with 2 Gy of external γ-irradiation. These changes may be adaptive responses because no changes occurred in cytokine or TGF-β/Smad gene expressions.