急性冠状动脉综合征合并糖尿病患者纤溶系统及血小板功能的研究——附68例报告

目的探讨ACS合并2型糖尿病患者纤溶系统及血小板最大聚集率的变化.方法256例ACS患者,根据其是否合并2型糖尿病分为糖尿病组(68例)及非糖尿病组(188例),并将100名同期在本院行体检的正常志愿者设为对照组.测定所有人员的组织型纤溶酶原激活物、纤溶酶原激活物抑制物-1含量及血小板最大聚集率,比较组间差异.结果糖尿病组血浆组织型纤溶酶原激活物含量[(5.5±1.7)μg/L]较非糖尿病组[(8.8±1.5)μg/L]低,而两组均较对照组[(9.7±2.8)μg/L]低(P＜0.01～P＜0.05).糖尿病组纤溶酶原激活物抑制物-1含量[(45±3)μg/L]较非糖尿病组[(35±3)μg/L]高,而两组均较对照组[(17±7)μg/L]高(P＜0.01～P＜0.05).糖尿病组血小板最大聚集率[(78±14)%]明显高于非糖尿病组[(66±11)%],而两组均较对照组[(56±14)%]高(P＜0.01～P＜0.05).结论ACS合并2型糖尿病患者与单纯ACS患者比较,其纤溶系统异常更明显,血小板凝聚性更强,提示此类患者应加强抗凝及抗血小板治疗.     

丹参-川芎水提取物有效组分配伍对大鼠心肌缺血/再灌注损伤的影响

目的 观察丹参-川芎水提取物有效组分配伍的注射液对大鼠心肌缺血/再灌注(I/R)损伤的影响.方法 将SD大鼠按随机数字表法分为假手术组、模型组、冠心宁组及丹参-川芎低、高剂量组,每组10只.采用结扎冠状动脉左前降支建立I/R损伤模型.于结扎成功后10 min股静脉注射给药,其中冠心宁组给予冠心宁注射液含生药2.88 g/kg,丹参-川芎低、高剂量组分别给予丹参-川芎水提取物有效组分注射液含生药2.43 g/kg和4.86 g/kg;假手术组和模型组给予等量生理盐水.于缺血40 min、再灌注120 min取血后处死动物,测定血中肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、6-酮-前列腺素F_(1a)(6-keto-PGF_(1a))、血栓素B_2(TXB_2)含量和血小板最大聚集率,并且测定心肌梗死程度.结果 丹参-川芎低、高剂量组心肌梗死面积((23.0±3.8)%、(20.8±4.7)%]较模型组[(29.1±3.2)%]显著降低(P＜0.05和P＜0.01);cTnT[(0.78±0.29)mg/L、(0.76±0.29)mg/L]和CK-MB[(891.5±252.5)U/L、(759.5±191.3)U/L]也较模型组[(1.04±0.14)mg/L,(1 268.2±256.5)U/L]显著降低(均P＜0.05),丹参-川芎高剂量组6-keto-PGF_(1a)较模型组升高[(206.7±35.6)ng/L比(138.6±28.9)ng/L,P＜0.05],血小板最大聚集率较模型组降低[(49.4±9.3)%比(77.1±16.7)%,P＜0.05].结论 丹参-川芎水提取物有效组分配伍可减小心肌梗死面积,降低I/R后cTnT、CK-MB含量,提高6-keto-PGF_(1a)/TXB_2比值,从而减轻心肌I/R损伤.     

STF083010对大鼠肾脏缺血再灌注损伤的肾保护作用

目的探讨STF083010对大鼠肾脏缺血再灌注损伤(ischemia-reperfusion injury,IRI)的肾保护作用。方法健康雄性SD大鼠30只,随机分为假手术组、IRI组与STF083010组,每组10只。假手术组大鼠开腹后仅分离双侧肾动脉,不夹闭肾动脉;IRI组和STF083010组大鼠采用无创动脉夹同时夹闭左、右肾动脉45 min后放开,建立IRI模型;STF083010组大鼠建立IRI模型前2h腹腔注射STF083010 15mg/kg。缺血再灌注24h后,应用全自动生化仪检测3组大鼠血清尿素氮和肌酐水平,3组大鼠均行肾组织病理学PAS染色,采用免疫组织化学法检测肾组织XBP1、GRP78蛋白阳性表达率,采用实时荧光定量PCR检测肾组织XBP1、GRP78 mRNA表达水平。结果IRI组血清肌酐[(322.10±18.93)μmol/L]、尿素氮[(41.16±3.09)mmol/L]水平、肾小管损伤评分(202.50±9.15)高于STF083010组[(149.70±14.80)μmol/L、(25.22±3.81)mmol/L、129.50±5.49]和假手术组[(49.58±2.82)μmol/L、(7.56±0.70)mmol/L、25.88±1.46](P0.05),STF083010组高于假手术组(P0.05);IRI组和STF083010组大鼠肾组织GRP78蛋白阳性表达率[(27.16±3.98)%、(58.72±7.12)%]、GRP78 mRNA表达水平(0.086±0.007、0.335±0.023)、XBP1蛋白阳性表达率[(56.32±5.21)%、(29.83±3.78)%]、XBP1mRNA表达水平(0.172±0.053、0.088±0.054)高于假手术组[(4.86±2.30)%、0.015±0.001、(5.68±1.37)%、0.039±0.004](P0.05),STF083010组GRP78蛋白阳性表达率和GRP78mRNA表达水平高于IRI组,XBP1蛋白阳性表达率和XBP1mRNA表达水平低于IRI组(P0.05)。结论 STF083010可通过抑制XBP1表达,增加GRP78表达保护大鼠肾功能。     

正铁血红素改善链脲佐菌素诱导的糖尿病大鼠肝损伤

目的 探讨血红素加氧酶1(HO-1)诱导剂正铁血红素和抑制剂锌原卟啉对糖尿病大鼠肝功能的影响及相关机制.方法 以链脲佐菌素腹腔注射诱导糖尿病SD大鼠模型,大鼠分为对照组、糖尿病组、正铁血红素组和锌原卟啉组.应用试剂盒检测各组大鼠血清游离脂肪酸(FFA)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性,肝组织匀浆总抗氧化能力(TAOC)和丙二醛(MDA);逆转录-聚合酶链反应(RT-PCR)法检测肝脏组织白细胞介素1(IL-1)和肿瘤坏死因子α(TNF-α)mRNA表达水平.结果 与对照组比较,糖尿病组大鼠血清AST、ALT、肝组织MDA、IL-1、TNF-α mRNA水平均明显增高(P＜0.01或＜0.05),分别是(91.59±12.38) U/L vs (50.19±12.65)U/L、(45.64±9.68) U/L vs (15.55±7.79) U/L,(0.81±0.22) nmol/mg vs (0.50±0.08) nmol/mg、12.32±3.51vs 7.02±1.99、22.24±4.48 vs 10.54±2.36;TAOC下降(P＜0.05);与糖尿病组大鼠比较,正铁血红素组大鼠ALT、TNF-α表达水平明显下降,TAOC增高(P＜0.05或＜0.01);锌原卟啉组大鼠较糖尿病组大鼠FFA、ALT、AST、MDA均有明显上升(P＜0.05或＜0.01),而TAOC下降(P＜0.05).结论 HO-1诱导剂正铁血红素可改善糖尿病大鼠肝损伤,而其抑制剂则加重肝脏损伤.     

内皮细胞蛋白C受体基因6936A/G多态性和深静脉血栓形成相关性研究

目的 通过病例对照研究,了解内皮细胞蛋白C受体(EPCR)基因6936A/G多态性和深静脉血栓形成(DVT)的相关性,进一步了解EPCR在DVT形成中的重要性.方法 用ELISA法检测65例DVT患者和71名健康体检者的外周血血浆可溶性EPCR(sEPCR)水平;提取血细胞中的DNA,PCR扩增后将目的 片段EPCR基因直接测序,分析EPCR基因第6936位点的多态性.结果 ①正常对照组中,AG基因型组血浆sEPCR水平[(0.97±0.32)ng/L]明显高于AA基因型组[(0.61±0.24)ng/L](P＜0.01);DVT患者组中AG基因型组[(0.87±0.21)ng/L]亦明显高于AA基因型组[(0.50±0.18)ng/L](P＜0.01).②DVT组的血浆sEPCR水平[(0.68±0.32)ng/L]明显高于正常对照组[(0.54±0.22)ng/L](P＜0.05).③EPCR基因6936位点AG基因型分布频率DVT组高于正常对照组(P＜0.05).④AG基因型患DVT的危险性较AA基因型高(OR=2.75,95%可信区间为1.04～7.30)(P＜0.05).结论 血浆sEPCR水平与EPCR基因6936A/G多态性有关.DVT患者血浆sEPCR水平较正常人增高.EPCR基因6936 AG基因型者可能患DVT的风险高.     

烟碱对心肌缺血/再灌注损伤大鼠炎症细胞因子的影响

目的 探讨烟碱对心肌缺血/再灌注(I/R)损伤大鼠炎症细胞因子的影响.方法 50只健康雄性SD大鼠按随机数字表法分为假手术组、I/R组、烟碱高剂量(400μg/kg)组、烟碱低剂量(40μg/kg)组及α-银环蛇毒素(α-BGT,1μg/kg)组5组,每组10只.采用结扎心脏左冠状动脉前降支30 min、再灌注90 min制作大鼠心肌I/R损伤模型;假手术组仅穿线不结扎.制模前30 min各药物组颈静脉注射相应剂量药物干预,假手术组和I/R组给予等量生理盐水.于再灌注末取右颈动脉血,测定肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、IL-10浓度和肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)活性;然后处死动物,取缺血区心肌组织测定髓过氧化物酶(MPO)活性;采用免疫组化和逆转录-聚合酶链反应检测心肌组织细胞间黏附分子-1(ICAM-1)蛋白及mRNA表达,并观察心肌超微结构.结果 与假手术组比较,I/R组血浆TNF-α、IL-8、IL-10、CK-MB、cTnI、心肌MPO活性及ICAM-1蛋白和mRNA表达均显著升高[TNF-α(ng/L):158.7±32.7比31.5±5.8,IL-8(ng/L):0.71±0.06比0.30±0.04,IL-10(ng/L):69.0±7.8比41.4±4.3,CK-MB(U/L):2 540±169比1 120±102,cTnI(μg/L):26.2±4.6比0.9±0.2,MPO(U/g):4.2±0.6比1.6±0.4,ICAM-1蛋白:0.210±0.025比0.100±0.018,ICAM-1 mRNA:1.82±0.23比1.18±0.20,P＜0.05或P＜0.01],病理学显示心肌组织损伤较重.与I/R组比较,烟碱高剂量组血浆TNF-α、IL-8降低[TNF-α(67.3±9.8)ng/L,IL-8(0.47±0.04)ng/L],IL-10升高[(147.5±12.5)ng/L],CK-MB、cTnI及心肌MPO活性、ICAM-1蛋白和mRNA均降低[CK-MB(1 282±145)U/L,cTnI(4.7±1.4)μg/L,MPO(2.5±0.4)U/g,ICAM-1蛋白0.140±0.026,ICAM-1 mRNA 1.31±0.25,P＜0.05或P＜0.01],心肌组织损伤减轻;而烟碱低剂量组和α-BGT组上述指标与I/R组比较差异无统计学意义.结论 烟碱可阻断内皮细胞表达黏附分子,阻断中性粒细胞黏附、游出,改善抗炎/促炎反应平衡,从而拮抗大鼠心肌I/R损伤时的过度炎症反应.     

肺气肿对大鼠外周骨骼肌功能异常的影响

目的 观察肺气肿对大鼠外周骨骼肌生物力学、病理形态学及氧化代谢功能的影响.方法 采用随机数字表法将20只SD大鼠分为肺气肿组及对照组.通过向气管内滴注猪胰弹性蛋白酶将肺气肿组大鼠制作肺气肿动物模型,对照组大鼠则于相同时间点向气管内滴注生理盐水.于滴药后第20周时行大鼠原位腓肠肌生物力学测定,并检测肌纤维组分构成、毛细血管密度、肌细胞内脂褐素包涵体含量(LI/F)、一氧化氮合酶(NOS)在腓肠肌中的表达及肌肉组织匀浆中氧化代谢酶活性变化.结果 肺气肿组大鼠腓肠肌抗疲劳耐力降低,肌力半数恢复时间[(145.0±55.4)s]较对照组[(55.2±29.3)s]延长(P＜0.05),I型肌纤维比例[(16.0±5.0)％]较对照组[(30.7±4.1)％]降低(P＜0.05),Ⅱb/x型肌纤维比例[(27.3±4.8)％]较对照组[(11.0±3.2)％]增高(P＜0.05);毛细血管密度[(513.9±71.1)n/mm2]较对照组[(578.6±59.9) n/mm2]降低(P＜0.05);腓肠肌脂褐素包涵体含量(3.3±0.5)较对照组(1.7±0.4)增高(P＜0.05);腓肠肌组织中内皮细胞型NOS(eNOS)表达(1.9±0.5)较对照组(3.4±0.6)降低(P＜0.05),神经元型NOS(nNOS)表达与对照组间差异无统计学意义(P＞0.05),诱导型NOS(iNOS)在2组大鼠腓肠肌中均未见发现.结论 肺气肿可导致大鼠外周骨骼肌生物力学、病理形态学及氧化代谢功能发生异常改变.     

伊贝沙坦对高血压患者心肌纤维化的影响--附48例报告

目的:探讨血管紧张素Ⅱ受体拮抗药伊贝沙坦对高血压患者心肌纤维化的影响.方法:48例高血压患者服用伊贝沙坦150～300mg,每日1次,疗程24周.治疗前后测定血清Ⅲ型前胶原氨基末端肽(aminoterminal propeptide of type Ⅲ procollagen,PⅢP)、转化生长因子β1(transforming growth factorβ1,TGF-β1)及血浆血管紧张素Ⅱ(angiotensinⅡ,AngⅡ),并与正常对照组(30名)比较.结果:治疗前高血压组PⅢP[(7.3±1.9)μg/L]、TGF-β1[(25.6±3.0)μg/L]及AngⅡ浓度[(67±11)ng/L]均高于正常对照组[(4.5±1.2)μg/L、(10.4±2.1)μg/L、(41±11)ng/L],均为P＜0.05;伊贝沙坦治疗24周后PⅢP[(5.0±1.6)μg/L]、TGF-β1[(15.8±2.8)μg/L]浓度均比治疗前明显下降,均为P＜0.05;AngⅡ[(70±13)ng/L]则与治疗前比较无明显变化,P＞0.05.结论:伊贝沙坦能显著降低高血压患者血清中的胶原含量,降低TGF-β1浓度,因而有可能会减轻心肌纤维化.     

贝前列素钠对早期糖尿病肾病患者血清可溶性细胞间黏附分子1、C反应蛋白及尿微量白蛋白排泄率影响的临床观察

目的 观察贝前列素钠对早期糖尿病肾病(DN)患者的临床疗效.方法 测定27例糖尿病无肾病患者(糖尿病无肾病组)、48例早期DN(DN组)患者血清可溶性细胞间黏附分子1(sICAM-1)浓度,并将48例早期DN患者随机分为两组,常规治疗组和贝前列素钠治疗组,各24例,测定两组治疗前后sICAM-1、C反应蛋白(CRP)及尿微量白蛋白排泄率(UAER)的变化.结果 早期DN患者血清sICAM-1浓度[(1385±171) g/L与(943±167) g/L;t=1.034,P=0.002]明显高于糖尿病无肾病组.贝前列素钠治疗组与常规治疗组治疗前血浆sICAM-1、CRP及UAER浓度比较差异均无统计学意义(P均＞0.05),治疗后均较治疗前改善,差异均有统计学意义(P＜0.05或P＜0.01),且贝前列素钠治疗组较常规治疗组改善明显,差异均有统计学意义(P＜0.05或P＜0.01).结论 早期DN患者即存在血清sICAM-1浓度升高,贝前列素钠治疗显著降低早期DN患者血清sICAM-1、CRP及UAER浓度,对早期DN有保护作用.     

血小板反应蛋白-1对多囊卵巢综合征大鼠血清内分泌腺来源血管内皮生长因子及卵巢组织形态学的影响

目的探讨血小板反应蛋白-1(thrombospondin-1, TSP-1)对来曲唑诱导的多囊卵巢综合征(polycystic ovary syndrome, PCOS)大鼠血清性激素、内分泌腺来源血管内皮生长因子(endocrine gland-derived vascular endothelial growth factor, EG-VEGF)表达及卵巢组织形态学的影响。方法 50只雌性SD大鼠随机分为模型组30只和空白组20只,模型组将来曲唑1 mg/kg溶于质量分数1%羧甲基纤维素(carboxymethyl cellulose, CMC)溶液灌胃,2 mL/d,连续21 d,制备PCOS模型;空白组给予等体积质量分数1%CMC溶液灌胃,连续21 d。造模成功后,2组各处死10只大鼠。将模型组剩余20只大鼠随机分为PCOS组和治疗组各10只,空白组剩余10只大鼠为对照组,治疗组腹腔注射TSP-1溶液0.2 mL/d,PCOS组和对照组腹腔注射等体积生理盐水,均连续21 d。采用ELISA法检测血清睾酮、卵泡刺激素(follicle stimulating hormone, FSH)、黄体生成素(luteinizing hormone, LH)、TSP-1及EG-VEGF水平;采血后处死大鼠,取卵巢,称质量后行组织病理检查,采用免疫组织化学法检测卵巢组织TSP-1、EG-VEGF蛋白阳性表达率。实验过程中记录大鼠动情周期,计算药物处理前后大鼠体质量。结果空白组、对照组大鼠动情周期均正常,模型组应用来曲唑第13天动情周期消失,治疗组应用TSP-1第14天4只大鼠恢复规律的动情周期;PCOS组体质量增加值[(190.90±8.33)g]较治疗组[(165.00±10.36)g]、对照组[(170.30±9.30)g]大(P0.05),卵巢质量[(0.09±0.01)g]较治疗组[(0.07±0.01)g]、对照组[(0.07±0.01)g]大(P0.05),治疗组与对照组比较差异无统计学意义(P0.05);药物处理第22天,PCOS组睾酮水平[(92.01±15.46)nmol/L]高于对照组[(60.21±10.17)nmol/L]、治疗组[(62.26±9.68)nmol/L](P0.05),LH水平[(3.04±0.16)u/L]高于对照组[(2.50±0.20)u/L]、治疗组[(2.52±0.18)u/L](P0.05),TSP-1水平[(171.84±23.48)μg/L]低于对照组[(251.44±26.04)μg/L]、治疗组[(223.44±20.64)μg/L](P0.05);治疗组TSP-1水平低于对照组(P0.05),睾酮、LH水平与对照组比较差异无统计学意义(P0.05);3组FSH、EG-VEGF水平比较差异无统计学意义(P0.05);与PCOS组比较,治疗组大鼠卵泡和黄体数量略有增加,囊性扩张卵泡明显减少,颗粒细胞层增厚,排列紧密;3组TSP-1、EG-VEGF蛋白均呈阳性表达,PCOS组EG-VEGF蛋白强阳性表达率(80%)明显高于治疗组(0)和对照组(0)(P0.05),TSP-1蛋白强阳性表达率(50%)与治疗组(60%)、对照组(60%)比较差异无统计学意义(P0.05)。结论 TSP-1能改善PCOS大鼠血清性激素紊乱、卵巢排卵功能和卵巢组织形态,对卵巢组织EG-VEGF蛋白的表达有一定影响,其可能通过调节EG-VEGF发挥治疗PCOS的作用。     

JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, suppresses food intake and gastric emptying with the elevation of plasma peptide YY and glucagon-like peptide-1 in a dietary fat-dependent manner

The microsomal triglyceride transfer protein (MTP) takes part in the mobilization and secretion of triglyceride-rich lipoproteins from enterocytes and hepatocytes. In this study, we investigated the effects of diethyl-2-({3-dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl) amino] phenyl}acetyloxymethyl)-2-phenylmalonate (JTT-130), a novel intestine-specific MTP inhibitor, on food intake, gastric emptying, and gut peptides using Sprague-Dawley rats fed 3.1% fat, 13% fat, or 35% fat diets. JTT-130 treatment suppressed cumulative food intake and gastric emptying in rats fed a 35% fat diet, but not a 3.1% fat diet. In rats fed a 13% fat diet, JTT-130 treatment decreased cumulative food intake but not gastric emptying. In addition, treatment with orlistat, a lipase inhibitor, completely abolished the reduction of food intake and gastric emptying by JTT-130 in rats fed a 35% fat diet. On the other hand, JTT-130 treatment increased the plasma concentrations of gut peptides, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) but not cholecystokinin, in the portal vein in rats fed a 35% fat diet. These elevations in PYY and GLP-1 were also abolished by treatment with orlistat. Furthermore, JTT-130 treatment in rats fed a 35% fat diet increased the contents of triglycerides and free fatty acids in the intestinal lumen, which might contribute to the elevation of PYY and GLP-1 levels. The present findings indicate that JTT-130 causes satiety responses, decreased food intake, and gastric emptying in a dietary fat-dependent manner, with enhanced production of gut peptides such as PYY and GLP-1 from the intestine.     

Substance P in the dorsal motor nucleus of the vagus evokes gastric motor inhibition via neurokinin 1 receptor in rat

Many gastrointestinal stimuli result in gastric fundic relaxation. This information is integrated at the interface of vagal afferents and efferents in the dorsal vagal complex. Substance P (SP) is present in this region, and the neurokinin(1) receptor (NK(1)R) is highly expressed in preganglionic neurons of the dorsal motor nucleus of the vagus (DMN). However, its functional effects on vagal motor output to the stomach have not been investigated. Therefore, we determined the gastric motor effects of stereotaxic microinjection of SP and selective tachykinin receptor agents into the DMN of anesthetized rats. Dose-related decreases in intragastric pressure and antral motility were obtained on the microinjection of SP (135 and 405 pmol) into the DMN, without cardiovascular changes. Similar decreases in intragastric pressure were noted after the microinjection of [Sar(9),Met(O(2))(11)]SP (NK(1)R agonist; 135 pmol) but not senktide (NK(3)R agonist; 135 pmol) or vehicle. The gastric motor inhibition evoked by SP (135 pmol) was attenuated by prior microinjection of 2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-yl)-a mine (GR203040; 1 nmol; NK(1)R antagonist). Vagotomy or hexamethonium (15 mg/kg i.v.) completely abolished the gastric relaxation evoked by SP (135 pmol) microinjected into the DMN. We conclude that SP acts on NK(1)R preganglionic cholinergic vagal neurons in the DMN, which control enteric nonadrenergic noncholinergic motor inhibition of the fundus. The potential relevance is that an antiemetic site of action of NK(1)R antagonists may be in the DMN to prevent excitation of neurons controlling fundic relaxation, which is an essential prodromal component of emesis.     

Gastric emptying and release of incretin hormones after glucose ingestion in humans.

This study investigated in eight healthy male volunteers (a) the gastric emptying pattern of 50 and 100 grams of glucose; (b) its relation to the phase of interdigestive motility (phase I or II) existing when glucose was ingested; and (c) the interplay between gastric emptying or duodenal perfusion of glucose (1.1 and 2.2 kcal/min; identical total glucose loads as orally given) and release of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1(7-36)amide (GLP-1), C-peptide, insulin, and plasma glucose. The phase of interdigestive motility existing at the time of glucose ingestion did not affect gastric emptying or any metabolic parameter. Gastric emptying of glucose displayed a power exponential pattern with a short initial lag period. Duodenal delivery of glucose was not constant but exponentially declined over time. Increasing the glucose load reduced the rate of gastric emptying by 27.5% (P < 0.05) but increased the fractional duodenal delivery of glucose. Both glucose loads induced a fed motor pattern which was terminated by an antral phase III when approximately 95% of the meal had emptied. Plasma GLP-1 rose from basal levels of approximately 1 pmol/liter of peaks of 3.2 +/- 0.6 pmol/liter with 50 grams of glucose and of 7.2 +/- 1.6 pmol/liter with 100 grams of glucose. These peaks occurred 20 min after glucose intake irrespective of the load. A duodenal delivery of glucose exceeding 1.4 kcal/min was required to maintain GLP-1 release in contrast to ongoing GIP release with negligibly low emptying of glucose. Oral administration of glucose yielded higher GLP-1 and insulin releases but an equal GIP release compared with the isocaloric duodenal perfusion. We conclude that (a) gastric emptying of glucose displays a power exponential pattern with duodenal delivery exponentially declining over time and (b) a threshold rate of gastric emptying of glucose must be exceeded to release GLP-1, whereas GIP release is not controlled by gastric emptying.     

雌二醇对卵巢去势大鼠胃排空的调节作用及其机制研究

目的 探讨雌二醇（E2）对卵巢切除大鼠血浆胆囊收缩素（CCK）及胃组织内胆囊收缩素受体A（CCKA）表达水平的影响，以期阐明雌二醇调节胃肠道运动功能的机制。方法 给予卵巢切除大鼠殴替代治疗，用放射免疫分析法测定血浆CCK浓度、用孵mTc-DTPA液体试餐测定胃排空率，以及用Western blot法检测胃组织内CCKA的表达量。结果 E2呈剂量依赖性地抑制卵巢切除大鼠的胃排空，升高血浆CCK的浓度，同时引起胃组织内CCKA受体表达增高。结论 雌二醇对卵巢切除大鼠的胃排空具有抑制作用，这种作用是通过促进CCK的分泌以及上调胃内CCKA受体的表达实现的。     

回肠间置术对Ⅱ型糖尿病大鼠血糖影响的实验研究

目的观察回肠间置术（Ileal transposition IT）对链脲佐菌素（Streptozotocic STZ）诱发的非肥胖2型糖尿病大鼠降糖作用,并探讨其机制。方法 SD大鼠高糖高脂饮食加腹腔注射STZ建立糖尿病模型后,将成模大鼠随机分为手术组（IT组）、假手术组（S-IT组）、对照组（C组）,每组10只;分别检测各组大鼠术前、术后第1、2、4、8周空腹和口服葡萄后血糖、及血清胰高血糖素样肽-1（Glucagon-like-peptide-1 GLP-1）的变化。结果 IT组术后第8周糖尿病大鼠的空腹及餐后血糖由术前的（18.96±1.13）、（31.82±2.33）mmol/L下降到（6.73±1.78）、（12.46±2.54）mmol/L（P〈0.01）,空腹及餐后GLP-1值分别由（10.16±1.65）（、21.50±1.68）pmol/L上升到（24.23±1.75）（、89.74±2.96）pmol/L（P〈0.01）,IT组和S-IT组大鼠体重变化无差异性。结论回肠间置术可以有效的改善2型糖尿病大鼠的血糖,术后食物过早刺激末端回肠,引起GLP-1分泌的增加起着重要的作用。     

Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.

In type-2 diabetes, the overall incretin effect is reduced. The present investigation was designed to compare insulinotropic actions of exogenous incretin hormones (gastric inhibitory peptide [GIP] and glucagon-like peptide 1 [GLP-1] [7-36 amide]) in nine type-2 diabetic patients (fasting plasma glucose 7.8 mmol/liter; hemoglobin A1c 6.3 +/- 0.6%) and in nine age- and weight-matched normal subjects. Synthetic human GIP (0.8 and 2.4 pmol/kg.min over 1 h each), GLP-1 [7-36 amide] (0.4 and 1.2 pmol/kg.min over 1 h each), and placebo were administered under hyperglycemic clamp conditions (8.75 mmol/liter) in separate experiments. Plasma GIP and GLP-1 [7-36 amide] concentrations (radioimmunoassay) were comparable to those after oral glucose with the low, and clearly supraphysiological with the high infusion rates. Both GIP and GLP-1 [7-36 amide] dose-dependently augmented insulin secretion (insulin, C-peptide) in both groups (P < 0.05). With GIP, the maximum effect in type-2 diabetic patients was significantly lower (by 54%; P < 0.05) than in normal subjects. With GLP-1 [7-36 amide] type-2 diabetic patients reached 71% of the increments in C-peptide of normal subjects (difference not significant). Glucagon was lowered during hyperglycemic clamps in normal subjects, but not in type-2 diabetic patients, and further by GLP-1 [7-36 amide] in both groups (P < 0.05), but not by GIP. In conclusion, in mild type-2 diabetes, GLP-1 [7-36 amide], in contrast to GIP, retains much of its insulinotropic activity. It also lowers glucagon concentrations.     

急性肝炎患者胃动素、生长素和胰高血糖素样肽-1的变化

目的 观察急性肝炎患者胃动素、生长素、胰高血糖素样肽-1的变化,并探讨急性肝炎患者胃动力异常的病理机制.方法 石家庄市第一医院消化内一科2010年10月至2011年9月就诊的急性肝炎患者70例,其中男40例,女30例.健康志愿者35例,男20例,女15例.采用放射免疫法测定胃动素含量,酶联免疫法检测生长素和胰高血糖素样肽-1的血浆含量.结果 胃动素水平急性肝炎组与对照组相比明显升高,差异有统计学意义（P＜0.05）；急性黄疸型肝炎组胃动素升高水平较急性无黄疸型肝炎组显著,差异有统计学意义（P＜0.05）.生长素水平急性肝炎组与对照组相比明显升高,差异有统计学意义（P＜0.05）；急性黄疸型肝炎组较急性无黄疸型肝炎组升高,差异有统计学意义（P＜0.05）.胰高血糖素样肽-1水平急性肝炎组与对照组相比明显升高,差异有统计学意义（P＜0.05）；急性黄疸型肝炎较急性无黄疸型肝炎胰高血糖素样肽-1升高更显著,差异有统计学意义（P＜0.05）.结论 急性肝炎患者存在胃动素、生长素、胰高血糖素样肽-1分泌紊乱,可能与急性肝炎患者胃动力障碍有关.     

Glucagon-like peptide-1 receptors in the brain: controlling food intake and body weight

The peptide hormone glucagon-like peptide-1 (GLP-1) enhances glucose-induced insulin secretion and inhibits both gastric emptying and glucagon secretion. GLP-1 receptor (GLP-1R) agonists control glycemia via glucose-dependent mechanisms of action and promote weight loss in obese and diabetic individuals. Nevertheless, the mechanisms and cellular targets transducing the weight loss effects remain unclear. Two recent studies in the JCI provide insight into the neurons responsible for this effect. Sisley et al. reveal that GLP-1R agonist–induced weight loss requires GLP-1Rs in the CNS, while Secher et al. reveal that a small peptide GLP-1R agonist penetrates the brain and activates a subset of GLP-1R–expressing neurons in the arcuate nucleus to produce weight loss. Together, these two studies elucidate pathways that inform strategies coupling GLP-1R signaling to control of body weight in patients with diabetes or obesity.     

超声单平面法检测成年人胃排空率的初步研究

目的应用超声单平面法检测口服超声助显剂后的成年人胃排空率,并探讨其正常值范围。 方法选取2020年4月至5月武警浙江省总队医院体检中心志愿接受胃功能超声检查的健康体检者106例。依据年龄不同,将研究对象分为青年组（18~39岁）50例、中年组（40~59岁）39例、老年组（60~79岁）17例。应用超声单平面法,对106例正常志愿者进行胃底、胃体及胃窦超声检查。测量口服胃超声助显剂后即刻、30 min、60 min时胃底、胃体及胃窦部面积,并计算口服胃超声助显剂后30 min及60 min时胃排空率（GER₃₀、GER₆₀）。采用统计学方法计算正常值范围。 结果106例正常志愿者进行超声检查,其中胃窦部单平面测量成功率为100%（106/106）,胃体部为98.11% （104/106）,胃底部为97.17%（103/106）。正常成人胃底、胃体及胃窦横断面积随时间推移逐步递减。其中胃窦部GER₆₀较胃底部和胃体部GER₆₀低,差异均有统计学意义（t=3.10、3.93,P均<0.05）;胃窦部GER₃₀较胃体部GER₃₀低,差异有统计学意义（t=3.00,P<0.05）;而胃体部所测GER₃₀及GER₆₀与胃底部所测GER₃₀及GER₆₀相比差异均无统计学意义（P均>0.05）。不同性别组及不同年龄组胃排空率比较差异均无统计学意义（P均>0.05）。GER₃₀正常参考值的95%CI胃底、胃体、胃窦分别为30.77%~34.19%、32.99%~36.57%、29.41%~32.78%;GER₆₀正常参考值的95% CI胃底、胃体、胃窦分别为51.67%~55.31%、52.61%~56.44%、47.77%~51.16%。 结论应用超声单平面法可初步建立口服胃超声助显剂后胃排空率的正常参考值范围,为下一步临床推广应用奠定基础。     

Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats.

Wistar rats develop glucose intolerance and have a diminished insulin response to glucose with age. The aim of this study was to investigate if these changes were reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have previously shown could increase insulin mRNA and total insulin content in insulinoma cells. We infused 1.5 pmol/ kg-1.min-1 GLP-1 subcutaneously using ALZET microosmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg body weight) tolerance test, 2 h after removing the pump. 15 min after the intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23 mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/-0.43 mmol/liter). This decrease in glucose levels was reflected in the higher insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs. 395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min after glucose injection. GLP-1 treatment also increased pancreatic insulin, GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1 is therefore able to reverse some of the known defects that arise in the beta cell of the pancreas of Wistar rats, not only by increasing insulin secretion but also by inducing significant changes at the molecular level.