单纯高血糖诱发大鼠动脉粥样硬化的实验研究

目的以糖尿病大鼠为实验对象,研究单纯高血糖是否可诱发动脉粥样硬化,以及血脂和同型半胱氨酸在糖尿病大血管动脉粥样硬化中的作用。方法用高脂饲料+链脲佐菌素STZ腹腔注射诱导2型糖尿病模型,研究分为正常对照组(C组)、1个月模型组(DM1组)、3个月模型组(DM3组)、5个月模型组(DM5组),均定期测定血糖、体重、血脂等。用形态学方法观察糖尿病大鼠动脉粥样硬化的表现,抽血化验血脂,同型半胱氨酸和血糖水平。结果实验正常对照组颈动脉HE染色镜下可见血管光滑平整;第一月时镜下可见血管平滑肌稍紊乱;第3个月时光镜下可见动脉血管壁局限增厚,细胞核增多,可观察到泡沫细胞,第5个月时已形成脂纹;糖尿病各组与对照组比较血糖、三酰甘油、总胆固醇、低密度脂蛋白、同型半胱氨酸和果糖胺水平较对照组显著升高(P0.01)。结论单纯高血糖动物模型出现了明确的动脉粥样硬化部分特征性表现,说明高血糖是动脉粥样硬化的一重要原因;三酰甘油、高胆固醇、高低密度脂蛋白、高同型半胱氨酸及果糖胺的升高可能是糖尿病动脉粥样硬化的危险因素,其作用可能与内皮细胞受损,动脉壁局部炎症介质表达有关。     

白细胞表面分化抗原40配体在糖尿病患者下肢血管内皮细胞及平滑肌细胞中的表达

目的观察白细胞表面分化抗原40配体（CD40L）在糖尿病患者下肢血管内皮细胞及平滑肌细胞中的表达,探讨CD40L与糖尿病下肢血管病变发生发展的关系。方法选择2007年11月-2008年4月间因外伤或罹患糖尿病足、需要行截肢手术而在我院就诊的单纯糖尿病患者10例、糖尿病下肢血管病变者12例、非糖尿病单纯下肢血管病变者10例以及对照组8例。测定其血糖、血脂、糖化血红蛋白等,用免疫组织化学方法检测下肢动脉血管内皮细胞及平滑肌细胞中CD40L的表达,用计算机图像分析技术半定量检测CD40L的表达。结果糖尿病下肢血管病变组、单纯糖尿病组、单纯下肢血管病变组的CD40L表达均较对照组增强（P〈0．05）;糖尿病下肢血管病变组的CD40L表达较单纯糖尿病组和单纯下肢血管病变组增强（P〈0．05）;CD40L的表达与空腹血糖值呈正相关（r=0．542,P〈0．001）。结论CD40L是参与糖尿病血管病变的重要炎症因子,高血糖可促发CD40L过度表达。     

针刺对2型糖尿病大鼠动脉粥样硬化的作用及机制

目的用2型糖尿病模型大鼠,研究针刺对2型糖尿病动脉粥样硬化的作用,并对其机制进行探讨。方法制备2型糖尿病模型大鼠,随机分为3组,糖尿病模型对照组(模型组)、糖尿病模型针刺组(针刺组),正常对照组(对照组),治疗40d后,处死检测一般指标,并观察主动脉粥样硬化的发生及血中和动脉壁炎症介质的表达。结果(1)模型组、针刺组、对照组的空腹血糖、空腹血清胰岛素、稳态模式胰岛素抵抗指数依次呈降低趋势(P<0.01),而稳态模式胰岛β细胞功能指数呈增高趋势(P<0.01)。(2)针刺组甘油三酯、胆固醇、低密度脂蛋白胆固醇、游离脂肪酸、一氧化氮、肿瘤坏死因子α、白细胞介素6、C反应蛋白、血浆纤溶酶原激活物抑制因子1明显低于模型组(P<0.01),与对照组比较差异无显著性(P>0.05),而针刺组的高密度脂蛋白胆固醇则明显高于模型组(P<0.01)。(3)模型组动脉壁肿瘤坏死因子α,白细胞介素6的表达远远高于针刺组和对照组(P<0.01),而针刺组与对照组比较差异无显著性(P>0.05)。(5)镜下可见模型组泡沫细胞和脂纹的形成,以及平滑肌细胞的变形、迁移和形成纤维帽;而针刺组动脉壁结构改变较轻,仅见内皮细胞收缩,弹力纤维增生。结论炎症参与了糖尿病动脉粥样硬化的形成;针刺可明显改善糖尿病动脉粥样硬化,其机制可能与降低炎症及一氧化氮、甘油三脂、低密度脂蛋白、游离脂肪酸及胰岛素水平有关。     

贝那普利对不同血糖状态糖尿病大鼠肾脏细胞凋亡及相关基因表达的影响

腹腔注射链脲佐菌素建立SD大鼠糖尿病模型，TUNEL、免疫组化检测结果显示，糖尿病持续高血糖大鼠贝那普利处理组较未处理组。肾小管凋亡细胞明显减少，Bax表达减弱，肾小球Bcl-2蛋白表达增强（均P〈0．01）；糖尿病血糖波动大鼠贝那普利处理组较未处理组。肾小管凋亡细胞数、Bax和Bcl-2蛋白表达差异均无统计学意义。     

链脲佐菌素致糖尿病大鼠骨髓EPO、SCF浓度变化

目的探讨实验性糖尿病大鼠骨髓促红细胞生成素（EPO）、干细胞因子（SCF）在糖尿病红细胞形态功能改变中的作用。方法链脲佐菌素（STZ）65mg／kg一次性腹腔注射，72h后测尾静脉血糖，血糖≥16．65mmol／L视为糖尿病模型成功。用免疫组织化学方法检测骨髓组织中EPO的表达，采用双抗体夹心酶联免疫吸附测定法（ELISA）检测骨髓上清及血清中SCF分泌水平的变化。结果糖尿病组大鼠较正常对照组大鼠骨髓EPO分泌水平增高（P〈0．05），骨髓上清及血清中SCF分泌水平两组比较无统计学差异。结论糖尿病时EPO分泌水平增高，可能是机体的一种抗损伤反应；SCF分泌水平无明显变化。     

黄芪注射液对糖尿病非酒精性脂肪肝模型大鼠血糖、血脂及肝脏脂肪分化相关蛋白表达水平的影响

目的研究黄芪注射液对糖尿病非酒精性脂肪肝模型大鼠血糖、血脂及肝脏脂肪分化相关蛋白表达水平的影响。方法采用高糖高脂结合链脲佐菌素诱导Wistar大鼠糖尿病非酒精性脂肪肝模型;将大鼠随机分为对照组、模型组及黄芪注射液干预组,分别于实验8周、12周及16周检测大鼠血清血糖、三酰甘油（TG）、总胆固醇（TC）的表达水平;HE切片观察大鼠肝脏病理形态的改变;免疫印迹（western—blot）检测大鼠肝脏脂肪分化相关蛋白（ADRP）的表达水平。结果高糖高脂结合链脲佐菌素大鼠血糖、TG、TC增高,肝脏脂肪发生变性,糖尿病非酒精性脂肪肝模型构建成功。实验12周,干预组大鼠血清血糖、TG、TC水平均低于模型组,但差异无统计学意义（P〉0．05）,肝脏脂肪变性程度与模型组大鼠基本相当,炎细胞浸润程度较模型组程度轻;实验16周,干预组大鼠血清血糖及TG水平明显低于模型组,差异有统计学意义（P〈0．05）,肝脂肪变性程度较模型组明显减轻,炎细胞浸润基本消失;与正常对照组相比,NAFLD大鼠肝脏ADRP水平显著增高（P〈0．05）,通过黄芪注射液治疗后,NAFLD模型肝脏ADRP的表达水平下调。结论黄芪注射液可改善NAFLD大鼠血糖血脂代谢紊乱,减轻肝脏的炎症反应和变性,具有一定的肝脏保护作用。     

牛磺酸对链脲佐菌素糖尿病大鼠胰岛β细胞的保护作用

利用链脲佐菌素诱导的Wistar糖尿病大鼠观察牛磺酸对其的防治作用。结果表明：①正常大鼠口服牛磺酸（8g·kg-1／d）对血糖和血清胰岛素浓度无明显影响；②糖尿病大鼠服用牛磺酸后可明显抑制其高血糖效应（P＜0．05，0．01，0．001）；③对链脲佐菌素诱致的大鼠血清胰岛素浓度的降低，牛磺酸具有明显的反转作用（P＜0．05，0．01，0．001）；④免疫组化结果表明，经牛磺酸防治的糖尿病大鼠表达胰岛素的胰岛数量较对照组显著增多（P＜0．05）。提示牛磺酸具有对抗和修复链脲佐菌素所引起的大鼠胰岛β细胞损伤的作用。     

糖尿病大鼠脑缺血再灌注后脑组织细胞凋亡与Bax、Be1-2及p53基因表达

目的观察糖尿病性高血糖大鼠脑缺血再灌注后脑组织细胞凋亡与Bax、Bc1-2和p53表达情况。方法将Wistar大鼠随机分成正常对照组、假手术组、正常血糖脑缺血再灌注组（NIR）和糖尿病性高血糖脑缺血再灌注组（DIR），采用链脲佐菌素腹腔注射制作糖尿病模型、线栓法制作大脑中动脉缺血再灌注模型，应用TUNEL法和免疫组化法分别检测细胞凋亡和Bax、Bc1-2及p53表达。结果与假手术组和正常对照组比较，NIR组凋亡细胞百分率和Bax、Bc1-2、p53表达明显增加（P均〈0.01）；与NIR组比较，DIR组凋亡细胞百分率和Bax、p53表达明显增加，Bc1-2表达明显降低（P均〈0.01）。结论糖尿病性高血糖大鼠脑缺血再灌注后梗死周边区细胞凋亡增加是高血糖加重缺血性脑损伤的机制之一；Bax和p53表达上调、Bc1-2表达下调参与了糖尿病大鼠脑缺血再灌注后细胞凋亡的调控。     

冠心病合并糖尿病患者血清超敏C反应蛋白水平与冠脉病变特点关系分析

目的探讨冠心病合并2型糖尿病患者冠状动脉病变与血清超敏C反应蛋白（hs—CRP）的相关性。方法经冠状动脉造影确诊冠心病患者，并根据既往或入院后OGTT试验结果分为合并2型糖尿病组和非糖尿病组，检测其hs-CRP、血糖、血脂水平及平均动脉压，并对合并2型糖尿病组冠状动脉病变程度与hs—CRP、血糖、血脂水平、平均动脉压、性别及吸烟史等因素作Logistic回归分析。结果冠心病合并2型糖尿病组hs—CRP水平及冠脉病变程度明显高于非糖尿病组（均P〈0.05）。Spearman秩相关分析表明，冠心病合并2型糖尿病组及非糖尿病组hs-CRP水平与冠状动脉病变支数均呈正相关（无糖尿病组r=0．827，P〈0．01；合并糖尿病组r=0．897，P〈0．01）。Logistic回归分析表明，年龄、吸烟史、hs—CRP、血糖、低密度脂蛋白及总胆固醇等是冠心病合并2型糖尿病患者冠脉病变严重程度的危险因素（均P〈0．05），且hs—CRP是其中最重要的危险因素；而性别、甘油三酯、高密度脂蛋白及平均动脉压不是冠心病合并2型糖尿病患者冠脉病变严重程度的危险因素（均P〉0．05）。结论冠心病合并2型糖尿病组炎症反应水平明显强于非糖尿病组，且患者炎症反应水平与冠脉损伤正相关；糖尿病可能通过炎症反应促进冠心病的发生及发展。监测冠心病合并2型糖尿病患者血清hs—CRP水平，对预测其冠状动脉粥样硬化病变的严重程度有一定意义。     

左卡尼汀治疗2型糖尿病合并冠心病的临床观察

目的：观察左卡尼汀对2型糖尿病合并冠心病患者心肌缺血症状，血糖、血脂、游离脂肪酸的影响。方法：62例2型糖尿病合并冠心病患者被随机分为左卡尼汀组及常规治疗对照组（对照组）。在常规治疗基础上左卡尼汀组加用左卡尼汀治疗，观察治疗前后心肌缺血症状，检查超声心动图及测定治疗前后血糖、血脂、游离脂肪酸浓度，并与对照组比较，分析其治疗效果。结果：左卡尼汀组与对照组相比，对心肌缺血症状有明显改善，胸闷、胸痛、乏力缓解率显著下降（P〈0．05）。左卡尼汀组血糖、血脂、游离脂肪酸水平均显著下降（P均〈0．05）；与对照组比较，血脂、游离脂肪酸水平显著下降（P〈0．05），且无严重副作用。结论：左卡尼汀治疗2型糖尿病合并冠心病患者可改善患者心肌缺血，同时降低血脂、游离脂肪酸，且有辅助降糖作用，对糖尿病合并冠心病患者有益。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.