大豆异黄酮对Ⅰ型糖尿病甲基乙二醛水平及白内障并发症的影响

目的:甲基乙二醛(MG)是糖代谢产生的毒性副产物,本研究旨在探讨大豆异黄酮是否通过降低MG的产生而发挥对I型糖尿病的防治作用。方法:链脲佐菌素诱导I型糖尿病大鼠模型,给予含不同剂量大豆异黄酮的大鼠饲料喂养,按大豆异黄酮不同剂量随机分为3组:大豆异黄酮低剂量组(diabetes+LIS),大豆异黄酮高剂量组(diabetes+HIS)及模型组(diabetes)。治疗8周后处死大鼠,留取血清测定血糖、糖化血红蛋白、还原型谷胱甘肽(GSH)、胰岛素水平,HPLC法测定血清MG水平,免疫组化法检测胰岛β细胞胰岛素表达情况。结果:与模型组或diabetes+LIS组大鼠比较,HIS组大鼠血清胰岛素水平明显上升[(2.46±0.35)μg/L vs(0.55±0.04)μg/L or(0.39±0.04)μg/L,均P0.01],血糖明显下降[(19.50±1.85)mol/L vs(28.24±3.56)mol/L or(26.94±1.82)mmol/L,均P0.05]、糖化血红蛋白减低[(13.14±3.00)%vs(17.16±2.60)%or(17.29±4.12)%,均P0.05],血清MG明显降低[(0.77±0.09)nmol/L vs(1.57±0.17)nmol/L or(1.91±0.28)nmol/L,均P0.05],而血清GSH水平明显增加[(13.26±1.61)mmol/L vs(7.35±1.55)mmol/L or(5.54±1.10)mmol/L,均P0.01],diabetes+HIS组大鼠胰岛β细胞中胰岛素表达水平也明显增加。Diabetes+HIS组大鼠白内障的发生率明显低于模型组(P0.05)。模型组与diabetes+LIS组比较,上述指标均无显著差异。结论:大豆异黄酮对I型糖尿病具有治疗作用,并能降低I型糖尿病大鼠白内障的发生率,其机制可能与胰岛素水平增加、MG水平降低及抗氧化作用有关。     

罗格列酮对2型糖尿病心肌能量底物代谢的影响

目的：探讨在2型糖尿病中胰岛素抵抗(IR)对心肌能量底物代谢以及心功能的影响。 方法： 采用高脂喂养(40％脂肪、42％碳水化合物和18％蛋白)4周及链脲佐菌素(STZ，35 mg/kg)1次性腹腔注射建立2型糖尿病大鼠模型，成模后随机分为2组：实验对照组(fat-fed/STZ)继续高脂喂养，实验治疗组(fat-fed/STZ/RSG)给予罗格列酮(RSG) 3 mg·kg-1·d-1治疗2周；正常对照组(chow-fed)为普通饮食喂养(12％脂肪、60％碳水化合物和28％蛋白)。左室插管检测心功能后进行30 min等容离体心脏灌注，灌注液含100 μU胰岛素、3％BSA、5 mmol/L葡萄糖、0.4 mmol/L［3H］软脂酸，测定样品葡萄糖摄取量及［3H2O］计数，评估葡萄糖和脂肪酸氧化率。 结果： 高脂喂养加小剂量STZ所制备模型鼠的血糖、血浆胰岛素及FFA水平均高于正常鼠,与临床2型糖尿病的代谢特征相似。成模2周后，fat-fed/STZ组大鼠与chow-fed组比较，30 min心肌葡萄糖总氧化量明显减少［(54.7±6.2 vs 69.0±5.7)μmol/g干重，P<0.01］。葡萄糖氧化率由25％降至18％，脂肪酸氧化率由75％增加到82％；同时，心功能检查显示左室EDP明显增加［(14.3±1.8 vs 10.5±1.1) mmHg，P<0.05］，-dp/dtmax降低［(550±57 vs 650±42) mmHg/s，P<0.01］，而+dp/dtmax无明显改变。与fat-fed/STZ组比较，fat-fed/STZ/RSG组大鼠的血糖明显改善［(9.0±4.6 vs 15.1±3.3) mmol/L，P<0.01］，血浆胰岛素减少(P<0.05)，FFA降低［(2.2±0.8 vs 3.3±0.8) mmol/L, P<0.05］；心肌葡萄糖的总氧化量升高到(63.5±6.4)μmol/g。干重，葡萄糖和脂肪酸的氧化率分别为24％和76％，基本达到chow-fed组水平(P>0.05)；EDP和-dp/dtmax均得到明显的改善(P<0.05)。 结论： IR导致2型糖尿病心肌能量底物代谢的异常和左室舒张功能的降低，早期使用RSG改善IR，不仅能提高心肌对葡萄糖的利用、降低脂肪酸氧化，也有助于改善心功能。     

C57BL/6哮喘小鼠细胞内镁含量与肺组织β2受体mRNA表达的相关性研究

目的：探讨细胞内镁含量对C57BL/6哮喘小鼠肺组织β₂受体mRNA表达的影响。方法:健康4－6周龄清洁级雌性C57BL/6小鼠96只，体重(12±2)g，随机数字表法分为A、B、C、D 4组，每组各24只。应用鸡卵蛋白(OVA)建立哮喘小鼠模型。A、B组予低镁饲料喂食，C、D组予正常镁饲料喂食。B、D组腹腔内注射沙丁胺醇诱导β₂受体低调节，A、C组腹腔内注射生理盐水作对照。第1 d、21 d、34 d各组分别随机抽取8只检测血浆Mg2+、红细胞内Mg2+、肺组织β₂受体mRNA及蛋白表达。 结果:1 d血浆Mg2+、红细胞内Mg2+、肺组织β₂AR mRNA及蛋白表达各组间差异无显著（均P>0.05）。21 d、34 d C组血浆Mg2+、红细胞内Mg2+、肺组织β₂AR mRNA及蛋白表达均显著高于A组［21 d：(0.84±0.09)mmol/L vs （0.57±0.10)mmol/L、(2.39±0.14)mmol/L vs （2.11±0.08)mmol/L、(0.75±0.09)mmol/L vs （0.59±0.06)pmol/g、（88.50±8.50)pmol/g vs （60.10±7.70)pmol/g，均P<0.05；34 d：(0.67±0.10)mmol/L vs (0.51±0.09)mmol/L、(2.17±0.08)mmol/L vs (2.05±0.09)mmol/L、(0.61±0.05)pmol/g vs (0.53±0.06)pmol/g、(76.60±7.10)pmol/g vs (58.00±7.60)pmol/g，均P<0.05］；21 d、34 d D组血浆Mg2+、红细胞内Mg2+、肺组织β₂AR mRNA及蛋白表达亦显著高于B组［21 d：(0.95±0.33)mmol/L vs (0.46±0.09)mmol/L、(2.32±0.18)mmol/L vs (1.87±0.14)mmol/L、(0.73±0.10)pmol/g vs (0.43±0.07)pmol/g、(96.90±8.00)pmol/g vs (47.90±4.90)pmol/g，均P<0.05；34 d：(0.71±0.10)mmol/L vs (0.31±0.08)mmol/L、(1.66±0.13)mmol/L vs (1.45±0.16)mmol/L、(0.40±0.07)pmol/g vs (0.33±0.05)pmol/g、(61.50±3.20)pmol/g vs (35.30±7.10)pmol/g，均P<0.05］。结论:细胞内镁缺乏的C57BL/6哮喘小鼠肺组织β₂受体表达减少，在激动剂作用下更易发生β₂受体低调节。     

脾切除对门脉高压症大鼠CD4、CD8和脾功能的影响

目的:研究肝硬化门脉高压症（PHT）大鼠脾次全切除术后CD4、CD8与脾功能的变化。 方法: 皮下注射60％四氯化碳复制大鼠肝硬化模型。共分5组：正常大鼠组、肝硬化（PHT）组、正常大鼠脾切除组、PHT全脾切除组、PHT脾次全切除组，每组10只。手术后第4周检测各组血常规、肝功能、tuftsin、CD4、CD8等指标。 结果:PHT高压症大鼠脾切除术后tuftsin水平［（171±21）ng/L vs （433±44） ng/L,P<0.01］、CD4/CD8（2.01±0.22 vs 1.12±0.12, P<0.01)均显著低于PHT组;PHT大鼠脾次全切除组tuftsin［（434±42）ng/L vs （171±21）ng/L, P<0.01］、CD4/CD8 （1.97±0.18 vs 1.12±0.12, P<0.01)显著高于PHT大鼠脾切除组。肝功能两者无显著差异（P>0.05）。 结论: PHT脾次全切组大鼠术后免疫和脾功能比PHT脾全切组大鼠明显改善，肝功能两者无显著变化。     

两种不同胰岛素抵抗状态的大鼠高脂联素血症产生的机制研究

目的:初步探讨胰岛素抵抗的Zucker肥胖大鼠(ZF鼠)及嘌呤霉素(PA)诱导的肾病综合征(DN)大鼠高脂联素(ADPN)血症的产生机制。方法:8周龄肥胖Zucker大鼠(ZF大鼠)正常饮食4周,及Wistar大鼠腹腔注射PA后10 d留取血、24 h尿标本,检测血脂系列、ADPN、白蛋白(ALB)及24 h尿白蛋白排泄率(UAER);并行多次取样的静脉糖耐量试验(FSIVGTT),根据Bergman微小模型法计算胰岛素敏感性指数(SI)及葡萄糖效应指数(SG);留取大鼠附睾白色脂肪组织称重。分析ADPN与各指标的相关性。结果:ZF大鼠及PA注射大鼠ADPN水平均显著高于对照组［(7.44±1.23）mg/L vs （2.44±0.33)mg/L及(8.64±0.88）mg/L vs （2.95±0.46)mg/L, P<0.0)］。ZF大鼠SI、SG显著降低且与ADPN负相关;DN大鼠SI、SG与对照鼠比较无明显变化,且与ADPN无相关性。两种大鼠模型均有明显高脂血症并与ADPN正相关。ZF鼠及DN鼠尿白蛋白排泄显著增多［(64.8±14.2) mg/24 h vs (14.9±14.6)mg/24 h及(275.1±64.5)mg/24 h vs (15.4± 4.5)mg/24 h, P<0.01］且与ADPN显著正相关。ZF大鼠白色脂肪比例高于对照鼠,但与ADPN升高水平不成比例,DN大鼠白色脂肪组织无增多。两种大鼠肌酐清除率与对照组比较均无显著差别。结论:ZF大鼠及PA注射鼠呈高ADPN血症,胰岛素敏感性与ADPN无关;两种大鼠UAER明显升高可能是高ADPN血症发生的主要机制。     

限食对高脂喂养大鼠肝脏内质网应激的影响

目的：观察限食对高脂喂养大鼠肝脏内质网应激标志伴侣蛋白78 kD糖调节蛋白（GRP78）mRNA表达的影响，以进一步了解饮食控制对肥胖及胰岛素抵抗影响的机制。方法：雄性Wistar大鼠24只，随机分为正常对照组（NC）、高脂饮食组（HF）、热卡限制组（CR），每组8只。NC组和HF组分别给予普通饲料（脂肪热卡比18.94%）和高脂饲料（脂肪热卡比50.55%）喂养12周，自由进食。CR组给予自由高脂饲料8周后，改为半量正常饲料（半量为同龄对照组自由进食量的一半）继续喂养4周。造模结束后检测动物胰岛素抵抗指数（HOMAIR）、内脏脂肪重量/体重比值和血清生化指标变化，光镜和电镜下观察大鼠肝脏组织学改变，RT-PCR半定量检测大鼠肝脏GRP78 mRNA的表达。结果：（1）HF组空腹血胰岛素(FIns) (27.51±3.51) mU/L vs (15.46±2.25) mU/L、甘油三酯（TG）(1.35±0.25) mmol/L vs (0.67±0.10) mmol/L、胆固醇（TC）(2.59±0.34) mmol/L vs (1.41±0.28) mmol/L及胰岛素抵抗指数HOMAIR(5.85±0.23) vs (2.85±0.60)较NC组明显升高(P＜0.01)，且肝脏中脂质沉积明显。（2）限食4周后，CR组的Fins(11.25±2.42) mU/L vs (27.51±3.51) mU/L、TG(0.45±0.06) mmol/L vs (1.35±0.25) mmol/L、TC(1.06±0.15) mmol/L vs (2.59±0.34) mmol/L和HOMAIR(1.91±0.38) vs (5.85±0.23)明显低于HF组(P＜0.01)，同时肝脏中脂质沉积也减轻。（3）电镜下，HF组内质网肿胀断裂，核糖体脱落，糖原溶解，CR组则基本恢复正常。（4）HF组大鼠肝脏中GRP78 mRNA表达明显高于NC组（29.36±3.54 vs 16.51±1.73），而CR组则明显低于HF组（13.70±2.35 vs 29.36±3.54）。结论：合理限制饮食能有效减轻高脂喂养所致的脂质代谢紊乱和胰岛素抵抗，其作用机制至少与肝脏组织中的内质网应激相关蛋白GRP78的mRNA表达受抑有关。     

苯那普利对自发性高血压大鼠肾脏Aquaporin 2表达的影响

目的：观察苯那普利对水孔蛋白2（AQP2）表达的影响。 方法： 雄性自发性高血压大鼠（SHR）16只，8周龄，体重200-300 g，随机分成2组，每组8只，分别给予生理盐水（SHRctrl）、苯那普利（SHRben）灌胃。灌胃8周后断头取血，放免法测定血浆血管升压素（AVP）浓度。取肾脏近髓组织100 mg，RT-PCR法检测大鼠肾脏AQP2 mRNA的表达，另取相应组织以免疫组化法检测AQP2的表达情况。 结果: SHRctrl组和SHRben组大鼠药物干预前血压无明显差异，大鼠苯那普利灌胃8周后，血压明显下降，显著低于SHRctrl组大鼠血压［（112±17）mmHg vs (169±9) mmHg，P<0.05］。SHRben组大鼠肾脏AQP2 mRNA（0.48±0.11 vs 0.72±0.17，P<0.05）、AQP2蛋白表达水平（0.47±0.09 vs 0.62±0.12, P<0.05）、血浆AVP浓度［（61.79±9.19）ng/L vs (87.16±8.20)ng/L, P<0.05］均显著低于SHRctrl组。 结论： 苯那普利抑制SHR肾脏水孔蛋白2的高表达。     

内皮细胞Jagged1下调促进PDGF诱导的大鼠平滑肌细胞增殖迁移

目的： 探讨内皮细胞Jagged1表达对PDGF诱导的大鼠血管平滑肌细胞增殖迁移的调节作用。方法: 分离培养大鼠主动脉内皮和平滑肌细胞,将内皮接种于下室、平滑肌接种于上室建立细胞共培养体系,根据内皮是否行Jagged1小RNA干扰分为对照组、空载体组和Jagged1小RNA干扰组。用Western blotting检测内皮细胞Jagged1的干扰效率。于下室加入PDGF（10 μg/L）干预24 h后分别用［3H］-TdR 掺入和平滑肌迁移计数检测平滑肌细胞增殖迁移能力,用Western blotting检测平滑肌细胞α-SM-actin蛋白表达。结果: 与对照组相比空载体组内皮细胞Jagged1蛋白表达无明显差异,Jagged1小RNA干扰组内皮细胞Jagged1蛋白吸光度相对值明显降低（0.26±0.02 vs 0.67±0.02, P<0.05）;PDGF+空载体组平滑肌［3H］-TdR 掺入量和迁移数与PDGF组相比无明显差异,PDGF+Jagged1小RNA干扰组平滑肌［3H］-TdR 掺入量和迁移数高于PDGF组{［3H］-TdR 掺入(23 074±2 702)counts·min-1·well-1 vs (16 442±1 803)counts·min-1·well-1,n=5,P<0.05;迁移(27±4)cells/field vs (15±3) cells/field, n=5,P<0.05};PDGF+空载体组平滑肌α-SM-actin蛋白表达与PDGF组相比无明显差异,PDGF+Jagged1小RNA干扰组平滑肌α-SM-actin吸光度相对值低于PDGF组（0.25±0.06 vs 0.49±0.04, n=3,P<0.05）。结论: 内皮细胞Jagged1下调促进PDGF诱导的平滑肌细胞增殖迁移,提示血管内皮细胞Jagged1表达在维持平滑肌收缩表型、抑制平滑肌过度增殖迁移中起一定调控作用。     

实验性NIDDM大鼠的胰岛素抗性

采用放射免疫分析及放射配基受体分析,观察实验性NIDDM大鼠血清胰岛素、红细胞中cAMP以及红细胞胰岛素受体最大结合力。结果表明链脲霉素与高热量饲料诱发的NIDDM大鼠有明显的胰岛素抗性,即在高胰岛素水平(25.29±8.34μU/ml,P<0.001)的同时伴有明显的糖耐量减低(P<0.001)及高脂血症(血清甘油三脂2.15±0.66mmol/L,P<0.001;血清胆固醇2.82±0.44mmol/L,P<0.001)。实验还进一步表明这种胰岛素抗性与红细胞胰岛素受体最大结合力的降低(693.51±149.55cpm/10~5红细胞,P<0.001)一致。据此推测胰岛素受体结合力的降低可能是NIDDM胰岛素抗性的主要原因。     

丙酮酸乙酯对脓毒症小鼠肝细胞的保护作用

目的:研究丙酮酸乙酯(ethyl pyruvate,EP)对脓毒症小鼠肝细胞的保护作用。 方法:制作小鼠盲肠结扎穿孔模型，应用丙酮酸乙酯林格氏液(REPS)与乳酸钠林格氏液(RLS)对小鼠进行液体复苏，检测肝组织的抗氧化能力和肝功能改变。 结果:脓毒症小鼠抗氧化能力低于假手术组，P<0.01。应用REPS复苏显著提高肝组织抗氧化能力，REPS组肝组织丙二醛浓度低于RLS组［(48.18±5.98)μmol·g-1 protein vs (78.34±11.16)μmol·g-1 protein］，超氧化物歧化酶［(5.19±1.41)103U/g protein vs (3.20±1.08)103U/g protein］和总抗氧化能力［(7.02±1.79)103U/g protein vs (4.77±1.35)103U/g protein］高于RLS组, P<0.01；REPS组小鼠丙氨酸转氨酶低于RLS组，［(210.06±23.36)U vs (458.86±51.55)U］,P<0.01。 结论:丙酮酸乙酯具有显著的抗氧化效应，提高脓毒症小鼠肝细胞的抗氧化能力，改善肝功能。     

Inotropic reaction of myocardium rats with postinfarction and diabetic remodeling on extrasistolic influences

Studied inotropic reaction papillary muscles of rats with postinfarction and diabetic remodeling on extrasistolic influences. It was found, that excitability of myocardium rats raises at a diabetes induced streptozotocin. Postextrasistolic contraction of myocardium rats with postinfarction cardiosclerosis it was considerably oppressed, and rhythmoinitropic reaction of myocardium rats was comparable to reaction of intact myocardium at a diabetes induced streptozotocin. The combination postinfarction and diabetic influence is paradoxical promoted preservation postextrasistolic potentiation of myocardium rats.     

2型糖尿病非收缩性难愈伤口模型的建立

背景：目前糖尿病创口的难愈性给临床的治疗增加了极大地困难。 目的：建立2型糖尿病状态下非收缩性难愈伤口的动物模型。 方法：高脂饮食喂养联合低剂量链脲佐菌素诱导形成大鼠2型糖尿病模型,在其背部造成圆形创面,用硅树脂固定伤口,模拟人类创面愈合过程,病理切片检查创面周缘肉芽组织皮肤厚度、微血管密度、胶原纤维及胶原蛋白水平的变化。 结果与结论：与正常组相比,链脲佐菌素注射72 h后高脂饮食喂养大鼠的空腹血糖、血清三酰甘油及胆固醇均明显增加,差异有显著性意义(P < 0.05~0.01);创伤后第1,3,5,7,14天,糖尿病组与正常组相比皮肤厚度、微血管密度、胶原纤维及胶原蛋白水平均有明显下降(P < 0.01)。提示高脂喂养联合链脲佐菌素诱导大鼠2型糖尿病的方法简便有效;创伤后检测指标均证明糖尿病大鼠比正常大鼠创面难愈。     

黄芪多糖对早期糖尿病肾病大鼠足细胞nephrin和podocin表达的影响

目的: 观察黄芪多糖(APS)对糖尿病肾病(DN)大鼠足细胞裂孔隔膜蛋白分子(nephrin和podocin)表达的影响,探讨其防治DN的作用机制。方法: 24只健康雄性SD大鼠,随机抽取8只为正常对照组,其余大鼠链脲佐菌素(STZ)腹腔注射复制糖尿病模型,1周后经血糖浓度测量确定大鼠糖尿病建模成功,将造模大鼠分为STZ组(8只)和STZ+APS组(8只),各组分别干预8周。于干预后第2、5、8周检测大鼠血糖浓度;第8周末称量大鼠体重,计算肾指数,观察肾脏病理改变;检测24 h 尿蛋白总量t和 血尿素氮、血肌酐;蛋白免疫印迹法检测大鼠肾组织nephrin和podocin的表达水平。结果: 应用APS干预后,大鼠血糖、肾系数、24 h尿蛋白总量、血尿素氮和血肌酐明显降低(P<0.05),体重增加(P<0.05);病理改变减轻;nephrin和podocin蛋白表达增加(P<0.05)。结论: APS对DN肾脏的保护作用可能与维持足细胞nephrin和podocin的表达有关。     

Lack of cardiotoxic effect of isoproterenol in streptozotocin diabetic rats

Summary The well known cardiotoxic effect of isoproterenol (ISO) was investigated in normal and streptozotocin diabetic rats. Seven days after the subcutaneous injection of ISO (15 mg/kg) the hearts were perfusion fixed and 12 sections from each heart were stained (Masson's trichrome). ISO induced myocardial fibrosis was quantified at the light microscopic level according to established morphometric principles. Pulse rate and ST elevation were recorded by EEC (3 standard leads) before and after the ISO injection. Non-diabetic control animals showed marked fibrosis after ISO, but surprisingly the diabetic animals showed no fibrosis after ISO treatment. These findings were in accordance with an ISO induced ST elevation seen only among control animals although both groups showed the same degree of tachycardia. Insulin treatment prevented the protection against ISO and when streptozotocin was injected 24 h after the ISO a normal quantitative and qualitative appearance of the scar tissue was seen. It thus seems that streptozotocin diabetic rats are protected against the toxic effect of ISO, leaving the haemodynamic response unaffected. Which factor in the diabetic metabolism is reponsible for the present phenomenon is not known, but a defect in the signal transmission from the -receptor to the adenylcyclase is suggested as a possible explanation.     

Amelioration of diabetic microalbuminuria and lipid peroxidation by captopril.

Administration of captopril, a scavenger of oxygen derived radicals as well as an inhibitor of angiotensin converting enzyme, has been an efficient way of treating diabetic proteinuria. In the present study, we evaluate whether captopril can ameliorate diabetic proteinuria as an effect on oxidative stress in streptozotocin- induced diabetic rats (STZR). At four weeks after the injection of streptozotocin (50 mg/kg, i.v.), STZR (n = 5) exhibited microalbuminuria. The rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.6 +/- 0.3 mg/24hr in age-matched control rats (CR; n = 5) and STZR, respectively. Compared to CR, STZR also showed an extremely increased rate of urinary lipid peroxides (LPO) excretion, an index of oxygen derived radicals generation. The respective values for CR and STZR were 0.6 +/- 0.3 and 6.9 +/- 0.6 mumol/24 hr. Significant amelioration of urinary albumin and LPO excretion rate by the treatment of insulin (2 U/day) suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct effect of streptozotocin. Chronic administration of captopril, which did not cause any discernible effect on CR, significantly reduced the urinary albumin excretion rate and decreased LPO excretion in STZR. The urinary albumin excretion rate was significantly correlated with the LPO excretion rate (p = 0.0004). These results suggest that oxidative stress can be responsible for diabetic microalbuminuria, and captopril could diminish the lipid peroxidation and ameliorate the microalbuminuria in diabetic rats.     

Effects of melatonin on streptozotocin-induced diabetic liver injury in rats

This study investigated the possible protective effects of melatonin as an antioxidant against streptozotocin (STZ)-induced diabetic liver injury in rats. Wistar rats were divided into four groups: untreated control (UC), melatonin-treated control (MC), untreated diabetic (UD), and melatonin-treated diabetic (MD). Experimental diabetes was induced by a single-dose (60 mg/kg, intraperitoneally (ip)) STZ injection, and melatonin was injected (200 microg/kg/day, ip) for 4 weeks. Upon light and electron microscopic examination, we observed that melatonin improved the morphological and histopathological changes of the liver caused by diabetes. Malondialdehyde levels in the liver homogenates of UD rats were higher than those of controls and were markedly reduced after melatonin treatment. Although no significant difference was observed with respect to antioxidant status, the superoxide dismutase activity tended to be higher in the UD rats than in the treated rats. Our findings showed that melatonin administration partially reduced liver injury in STZ-induced diabetic rats.     

核黄素对STZ诱导的大鼠糖尿病肾病的治疗作用

目的:探讨核黄素对STZ诱导的大鼠糖尿病肾病的治疗作用及机制。方法:将雄性Sprague-Daw-ley大鼠随机分为3组,即正常对照组、糖尿病模型组、核黄素治疗组,采用腹腔注射链脲佐菌素法建立糖尿病大鼠模型,收集各组血、尿及肾组织,生化方法检测24h尿蛋白量、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性及丙二醛(MDA)的含量,并计算肾脏脏器系数(KW/BW);Western blotting检测不同组别肾皮质TGF-β1、纤溶酶原活化抑制因子-1(PAI-1)蛋白质水平;光镜观察肾组织形态改变。结果:与糖尿病模型组大鼠比较,核黄素治疗组大鼠尿蛋白量显著降低(P0.01),肾组织及血清SOD、CAT活性升高(P0.01),肾组织MDA含量显著降低(P0.01),核黄素治疗组肾皮质TGF-β1及PAI-1蛋白表达明显低于糖尿病模型组。结论:核黄素对STZ诱导的糖尿病大鼠肾脏有一定的保护作用,其机制可能与其降低肾组织TGF-β1、PAI-1蛋白表达有关。     

p-ERK1/2-AP-1通路在姜黄素抗大鼠糖尿病神经病理性痛中的作用

目的: 观察p-ERK1/2-AP-1通路在姜黄素(Cur)抗大鼠糖尿病神经病理性痛(DNP)中的作用。方法: 雄性SD大鼠96只,随机分为4组(n=24):正常对照组、DNP组、DNP+溶剂组(DNP+Sol组)和DNP+Cur 100 mg/kg组(DNP+Cur组)。除正常对照组外,其余各组采用腹腔注射链唑霉素75 mg/kg的方法制备DNP模型,造模成功后每天1次腹腔注射相应的溶剂或Cur,持续2周。于造模前2 d、造模后14 d、腹腔给药后3、7、14 d时测定机械缩足痛阈(MWT)、热缩足潜伏期(TWL)和非空腹尾静脉血糖值,取脊髓腰膨大及L₄/L₅背根神经节(DRG),采用免疫组化及Western blotting法测定脊髓背角和DRG p-ERK1/2的表达,电泳迁移率变动分析AP-1的表达。结果: 与正常对照组相比,DNP组各时点MWT降低、TWL缩短;血糖值升高;脊髓背角及DRG p-ERK1/2均出现表达上调(P<0.05);脊髓背角AP-1表达上调(P<0.05)。与DNP组相比,DNP+Cur组在给药后7 d MWT回升、TWL延长;在给药后14 d脊髓背角及DRG p-ERK1/2、脊髓背角AP-1表达下调(P<0.05),但并不影响血糖水平。结论: Cur可减轻大鼠糖尿病神经病理性痛,其机制可能与抑制脊髓背角和DRG神经元p-ERK1/2-AP-1通路激活有关。     

糖尿病大鼠股骨头血管内皮功能障碍的变化

背景：糖尿病骨病的并发症起病复杂,骨组织血管内皮病变可能是造成的一个重要原因。 目的：探讨糖尿病对大鼠股骨头内皮功能障碍的影响。 方法：将60只大鼠随机等分为对照组和糖尿病组,糖尿病组大鼠腹腔注射链脲佐菌素建立糖尿病模型。 结果与结论：造模15周时,与对照组相比,糖尿病组大鼠股骨头出现骨质疏松显微结构改变,血清一氧化氮水平明显降低,血浆内皮素1水平明显升高,糖尿病组股骨头凝血因子Ⅷ表达明显减少(P < 0.01),提示糖尿病前期就出现内皮功能障碍。微血管增生,糖尿病诱发内皮功能障碍及相互作用与大鼠股骨头功能减退有关。     

Comparison of renal calcium concentration in obese, lean, diabetic, and non-diabetic Zucker rats fed a magnesium-deficient fructose diet.

In order to determine the effects of hypoinsulinaemia or hyperinsulinaemia on nephrocalcinosis induced by the interaction between fructose and magnesium (Mg) deficiency, we compared kidney calcification in obese versus lean, and non-diabetic versus diabetic female Zucker rats fed a magnesium-deficient fructose diet. One half of the obese and lean animals, respectively, was injected with streptozotocin to produce diabetes, and the other half was injected with citrate buffer alone. Diabetic, non-diabetic, obese, and lean animals were divided into two dietary groups, consisting of high starch or high fructose without added Mg. After a four week period, 24 hour urine was collected for urinary output, protein, oxalate, citrate, MG, and calcium (Ca) measurements. The animals were then decapitated, and blood was collected for glucose, Mg, and Ca determinations, and kidneys were removed to determine their Mg and Ca contents. All fructose-fed animals exhibited significantly more kidney Ca then the starch-fed animals. Lean non-diabetic rats fed fructose showed the greatest kidney Ca along with the greatest urinary protein excretion among all experimental groups. The significant finding in the present study is that diabetes or obesity reduced nephrocalcinosis regardless of the insulin status of the rats. Diuresis and hypercitraturia in diabetic and/or obese animals may cause a reduction in nephrocalcinosis induced by the interaction between fructose and magnesium deficiency. Hyperproteinuria (uromucoid) in combination with hypercalciuria and hypomagnesuria may be responsible for greater nephrocalcinosis in the fructose than the starch group. The possible mechanisms for this interaction on nephrocalcinosis have been discussed.