Exendin-4通过上调pdx-1mRNA表达促进STZ造模小鼠β细胞增生

目的观察腹腔内注射exendin-4对链脲佐菌素(STZ)造模小鼠的血糖、胰岛数目和pdx-1表达的影响。方法C57BL/6小鼠30只被分成3组注射用水组、STZ50mg/kg 注射用水组和STZ50mg/kg exendin-40.1μg/g体重组。实验第1~10d每日腹腔内注射注射用水或exendin-4,实验第3~7d注射STZ。检测exendin-4注射期间和停药后血糖水平,停药后进行腹腔葡萄糖耐量试验(IPGTT)、胰腺胰岛计数和RT-PCR检测转录因子pdx-1的表达。结果STZ造模小鼠连续exendin-4注射期间平均血糖和注射用水组差异无统计学意义[(6.12±0.37vs6.21±0.41)mmol/L,P>0.05];而与未注射exendin-4的STZ小鼠组比较血糖明显降低[(6.12±0.37vs9.59±1.08)nmol/L,P<0.05];exendin-4停药后2周内的STZ exendin-4组的平均血糖仍较STZ 注射用水组明显降低[(13.02±1.96vs18.55±3.14)mmol/L,P<0.05]。IPGTT显示STZ exendin-4组的糖耐量较STZ 注射用水组明显改善,胰腺胰岛计数STZ exendin-4组较STZ 注射用水组增加了近1倍,转录因子pdx-1的表达也明显上调(P<0.05)。结论Exendin-4对STZ造模小鼠的血糖不仅具有短期控制作用,而且停药后仍有一定的维持作用。Exendin-4改善了STZ造模小鼠的糖耐量,上调了pdx-1的表达,促进了胰岛的增生。     

胰岛素短期强化治疗对初诊2型糖尿病患者胰岛β细胞功能的影响

目的　观察胰岛素短期强化治疗对初诊 2型糖尿病患者胰岛β细胞功能的改善作用及降糖效果。方法对 2 4例初诊 2型糖尿病患者应用胰岛素泵进行 2周的胰岛素强化治疗 ,治疗第 15天时对比治疗前后静脉葡萄糖耐量试验所诱发的胰岛素第 1时相的分泌、胰岛素曲线下面积及由 Homa模型计算胰岛素分泌指数 (Homa B)、胰岛素抵抗指数 (Homa A) ,同时观察空腹血糖、餐后 2小时血糖变化 ;3个月时对比糖化血红蛋白变化。结果　患者空腹血糖及餐后 2小时血糖分别在治疗 (3.7± 1.8)天、 (5 .5± 1.7)天达到控制标准 ,胰岛 β细胞功能显著改善 ,静脉葡萄糖耐量试验各时点的胰岛素分泌及 Homa B值较治疗前明显升高 (P<0 .0 5 ) ,Hom a A指数下降(P<0 .0 5 )。随访 3个月 ,13例患者单纯控制饮食即可维持血糖控制标准 ,糖化血红蛋白由治疗前的 (9.8± 1.2 ) %降至 (6 .3± 0 .7) %。结论　胰岛素短期强化治疗可明显改善及恢复初诊 2型糖尿病患者胰岛素第 1时相分泌 ,不同程度的缓解病情     

西洛他唑对OLETF大鼠胰岛素敏感性的影响

目的　探讨西洛他唑对自发 2型糖尿病的动物模型OLETF大鼠胰岛素敏感性的影响。　方法　将雄性OLETF大鼠在 32周龄时根据体重及胰岛素耐量试验中 5 0min血糖下降百分率随机分成三组 :正常喂养组 ,罗格列酮治疗组及西洛他唑治疗组 ,每组 7只鼠。测给药 2 9d后的血脂水平 ;给药 38d后测空腹血糖 ,以正常血糖高胰岛素钳夹技术对以上各组进行胰岛素敏感性评价。　结果　西洛他唑组血甘油三酯水平 ( 1.95± 0 .19mmol/L)较对照组 ( 3.11± 0 .32mmol L)降低 (P <0 .0 1) ;胆固醇 ( 1.32± 0 .17mmol/L)较对照组 ( 2 .2 6± 0 .17mmol/L)降低 (P <0 .0 1) ;游离脂肪酸 ( 0 .46± 0 .11mmol/L)较对照组 ( 1.5 3± 0 .35mmol/L)降低 (P <0 .0 5 ) ;葡萄糖输注速率 ( 11.0 4±1.12mg·kg- 1 ·min- 1 )较对照组 ( 7.33± 1.12mg·kg- 1 ·min- 1 )增加 (P <0 .0 1) ;空腹血糖 ( 6 .1± 0 .7mmol/L)较对照组 ( 7.87± 1.2 3mmol/L)有所下降 ,但差异无显著意义 (P >0 .0 5 )。　结论　西洛他唑能改善OLETF大鼠的胰岛素敏感性。     

孕中期妊娠期糖尿病患者胰岛素抵抗、胰岛素分泌功能变化及临床意义

目的探讨孕中期妊娠期糖尿病(GDM)患者胰岛素抵抗(IR)、胰岛素分泌功能变化及临床意义。方法选择孕中期孕妇60例,根据口服葡萄糖耐量试验结果,分为GDM组28例、正常糖耐量(NGT)组32例。检测两组各时间点的血糖、胰岛素,计算IR指数(HOMA-IR),评价IR程度;计算胰岛素分泌指数(HOMA-β)、动态胰岛素分泌指数(MBCI)、血糖曲线下面积(AUCGLU)/胰岛素曲线下面积(AUCINS),评价胰岛素分泌功能。结果与NGT组比较,GDM组的各时间点血糖、胰岛素、HOMA-IR、AUCGLU、AUCINS、HOMA-β明显升高(P均<0.05),MB-CI、AUCINS/AUCGLU明显降低(P<0.05或<0.01)。结论 GDM患者存在IR及胰岛素分泌功能降低,胰岛素分泌不能代偿IR是GDM发生的主要原因。     

长期脂肪含量较高饲料喂养对大鼠胰岛素抵抗的影响

目的探讨脂肪含量较高饲料长期喂养对大鼠胰岛素抵抗的影响。方法大鼠随机分为两组,对照组以普通饲料喂养16 w,高脂组以脂肪热量比38.5%的饲料喂养12 w,再以脂肪热量比51.3%的饲料喂养4 w。实验结束时,测定空腹血糖(FBG)、空腹血浆胰岛素(FINS)并计算胰岛素敏感指数(ISI)和胰岛素抵抗指数(HOMA-IR);另外进行口服葡萄糖耐量试验(OGTT),计算血糖曲线下面积(AUC)。结果两组大鼠能量摄取相似,体重差别不大。高脂组大鼠FINS显著高于对照组(P<0.01),但FBG无显著差别。高脂组大鼠ISI显著下降(P<0.01),HOMA-IR显著上升(P<0.01),血糖AUC显著升高(P<0.01)。结论脂肪含量较高的饲料喂养大鼠16 w后引起了胰岛素抵抗和糖耐量异常。     

三黄泻心汤对肥胖大鼠血清瘦素及胰岛素水平影响的实验研究

目的通过三黄泻心汤对肥胖大鼠体重、Lee’s指数、腹腔脂肪湿重及血清瘦素、胰岛素水平的影响,探讨清热解毒法对肥胖及瘦素、胰岛素抵抗的调整作用。方法给予高脂饮食建立营养性肥胖大鼠模型,将肥胖大鼠随机分为3组,分别给予三黄泻心汤(A组)、盐酸芬氟拉明(B组)和生理盐水(C组)灌胃,连续12周,每周测体重,试验末取血测血脂、血清瘦素及胰岛素。结果A组和B组大鼠体重分别为(387.8±12.1)g和(378.3±10.7)g较C组的(493.1±8.9)g低(P<0.05);腹腔脂肪湿重A组和B组也较C组低(P<0.01),且随喂养时间的延长体重变化趋势A组下降缓慢,B组亦下降,但试验末略有上升,C组体重继续增长。A组和B组血糖、胆固醇和低密度脂蛋白均较C组低,瘦素和胰岛素的变化A组和B组较C组亦低(P<0.05),且A组与C组血糖和胰岛素差异更大(P<0.01)。结论三黄泻心汤可能通过降低肥胖大鼠体重、血糖及血清瘦素、胰岛素水平而发挥调节血脂、改善瘦素和胰岛素抵抗的作用。     

胰岛素治疗对高脂喂养的糖尿病大鼠胰岛B细胞分泌变化的影响

目的观察胰岛素治疗对长期高脂喂养的糖尿病(DM)大鼠B细胞分泌功能的影响。方法2003-08~2004-11对华中科技大学同济医学院附属协和医院内分泌实验室的DM大鼠随机分为糖尿病正常饮食组(DN,n=10)、糖尿病高脂饮食组(DH,n=10)、糖尿病高脂饮食胰岛素治疗组(DHI,n=10)及正常Wistar大鼠正常饮食对照组(NC,n=10)。于胰岛素治疗后行口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT),并根据血糖和血胰岛素值计算糖负荷后胰岛素增值与血糖增值的比值(ΔI30/ΔG30)和修正的B细胞胰岛素分泌指数(MBCI)。留取空腹血浆测定游离脂肪酸(FFA)和甘油三酯(TG)。留取尾部胰腺组织测定胰腺内TG和FFA。结果与DN组和NC组相比,DH组血和胰腺内TG及FFA计量明显增多(分别为对DN组,P<0·01、P<0·01;对NC组,P<0·01、P<0·01;对DN组,P<0·01、P<0·05;对NC组,P<0·01、P<0·01),此外,ΔI30/ΔG30和MBCI显著降低(分别为对DN组,P<0·01、P<0·05,对NC组,P<0·01、P<0·01)。胰岛素治疗后,与DH组相比,胰腺内TG和FFA计量明显下降(分别为P<0·01、P<0·01),同时ΔI30/ΔG30、MCBI均得到明显改善(P<0·01、P<0·05)结论长期高脂饮食喂养可导致T2DM大鼠胰腺内FFA和TG沉积,并进一步损伤胰岛B细胞胰岛素的分泌;胰岛素治疗对高脂饮食所致的上述影响有一定的改善作用。     

老年糖耐量受损人群异质性分析

目的评价老年糖耐量受损人群伴或不伴胰岛素抵抗的分布比例,以及代谢综合征和动脉粥样硬化在伴胰岛素抵抗人群和不伴胰岛素抵抗人群中的发生情况。方法测定156例老年糖耐量受损人群体重指数(BMI)、腰臀比(WHR)、胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDLC),高密度脂蛋白胆固醇(HDLC)、血压、胰岛素、胰岛素曲线下面积(InsAUC)、胰岛素原(PI)、胰岛素原曲线下面积(PIAUC)、超敏C反应蛋白(hsCRP)、纤维蛋白原(Fg)等指标,并测量其颈动脉内膜中层厚度和动脉斑块的变化,根据HOMA胰岛素抵抗指数(HOMAIR)将糖耐量受损人群分为胰岛素抵抗组和非胰岛素抵抗组。结果(1)156例糖耐量受损患者中,胰岛素抵抗组118例(75.6%);非胰岛素抵抗组38例(24.4%);(2)胰岛素抵抗组BMI、WHR、TG、TC、LDLC、收缩压、舒张压、InsAUC、PIAUC、HOMAIRCRP及Fg分别为(26.8±2.1)kg/m2、0.96±0.23、(2.9±1.3)mmol/L、(5.4±1.8)mmol/L、(3.9±1.5)mmol/L、(154±12)mmHg、(96±7)mmHg、(239±71)mU/L、(170±42)pmol/L、(7.5±1.2)mg/L、(4.5±1.4)g/L,明显高于非胰岛素抵抗组(22.8±2.5)kg/m2、0.80±0.2、(1.7±1.2)mmol/L、(4.5±1.5)mmol/L、(3.0±0.8)mmol/L、、(133±10)mmHg、(83±1)mmHg、(180±66)mU/L、(109±25)pmol/L、(4.3±0.8)mg/L、(3.8±1.5)g/L(P<0.05或P<0.01);而HDLC明显低于非胰岛素抵抗组(1.0±0.4)mmol/L、(1.4±0.4)mmol/L(P<0.05);(3)与非胰岛素抵抗组比较,胰岛素抵抗组和非胰岛素抵抗组内膜中层厚度分别为〔(1.18±0.05)mm、(1.01±0.02)mm,P<0.01〕,动脉斑块的发生率在胰岛素抵抗组显著高于非胰岛素抵抗组,分别为17.8%和7.8%。结论老年糖耐量受损人群存在异质性,多数伴胰岛素抵抗,伴胰岛素抵抗者代谢综合征和动脉粥样硬化发生的危险性显著高于不伴胰岛素抵抗者。     

受体胸腺内注射Fas抗体对急性移植排异的作用及机制

目的:探讨胸腺内注射死亡受体(Fas)抗体对心脏移植急性排异、半胱氨酸基天冬氨酸特异性蛋白酶(Caspase-3)表达及心肌细胞凋亡的影响。方法:应用大鼠腹腔心脏移植模型(供体:Wistar大鼠,受体:SD大鼠),随机分为实验组、环孢素组和对照组。心脏移植前24h,向实验组受体胸腺内注射Fas抗体(0.1mg/kg)1次,腹腔注射生理盐水2mL1次/d;向环孢素组受体胸腺内注射磷酸缓冲液(PBS)(1mL)1次,腹腔注射环孢素(8mg/kg)1次/d;向对照组受体胸腺内注射PBS(1mL)1次,腹腔注射生理盐水(2mL)1次/d。术后5d取移植心脏,进行病理学检查,排斥分级;半定量逆转录聚合酶链反应(RT-PCR)检测移植心脏Caspase-3 mRNA表达;免疫组化检测Caspase-3蛋白表达;原位末端标记法(TUNEL)检测凋亡细胞。结果:1.排斥级别:实验组2.13±0.64低于对照组3.75±0.46高于环饱素组1.25±0.68(P<0.05);2.Caspase-3 mRNA水平:实验组0.62±0.05低于对照组0.87±0.12,高于环孢素组0.59±0.08(P<0.05);3.Caspase-3蛋白阳性细胞数:实验组113±12.5低于对照组223±4.80高于环孢素组95±4.50(P<0.05);4.凋亡指数:实验组7.32±0.58低于对照组11.07±1.18高于环孢素组5.67±0.43(P<0.05)。结论:受体胸腺内注射Fas抗体减轻心脏移植急性排异程度。机理是下调移植心脏Caspase-3基因mRNA及蛋白表达、减少心肌细胞凋亡。     

甲状腺功能亢进与胰岛素分泌功能和胰岛素抵抗的关系

目的探讨甲状腺功能亢进（甲亢）患者胰岛素分泌功能和胰岛素抵抗的变化。方法50例甲亢患者（甲亢组）行葡萄糖耐量试验,并以25例正常人作为对照组,分别测定两组空腹及餐后1、2h的血糖及胰岛素水平,计算胰岛素敏感指数、胰岛素抵抗指数及胰岛B细胞分泌功能指数并进行比较。结果甲亢组糖耐量正常15例,糖耐量减低25例,糖尿病10例。甲亢组胰岛素抵抗指数高于对照组,胰岛素敏感指数和胰岛B细胞分泌功能指数低于对照组,上述指标两组间比较差异均有统计学意义（P均〈0．05）。结论甲亢时可导致糖代谢紊乱,出现高血糖及高胰岛素血症,发生胰岛B细胞分泌功能下降及胰岛素抵抗。     

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.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

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.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.