葛脾煎剂对2型糖尿病大鼠血糖、血脂的影响

目的:探讨葛脾煎剂对实验性糖尿病大鼠血糖、血脂及胰岛素的影响.方法:利用链脲佐茵素建立2型糖尿病大鼠动物模型.将其随机分为糖尿病模型组(n=11)、葛脾煎剂组(n=11)及二甲双胍组(n=9),并设置正常对照组(n=10).治疗8周,观察治疗期间及治疗后大鼠的一般状况,检测大鼠血糖、总胆固醇(TC)、甘油三脂(TG)、血胰岛素,并计算胰岛素敏感指数(ISI).结果:葛脾煎荆可改善糖尿病大鼠基本状况,治疗组与糖尿病模型组比较,血糖、TC、TG、空腹胰岛素明显降低(P＜0.05),ISI明显提高.二甲双胍组血糖下降幅度、ISI提高幅度大于葛脾煎剂组(P＜0.05),胰岛素下降幅度及血脂改善程度两治疗组无明显差异(P＞0.05).结论:葛脾煎剂对糖尿病大鼠具有降糖、改善血脂、提高胰岛素敏感性的作用,其疗效与二甲双胍相似.     

明日叶查尔酮对2型糖尿病大鼠骨骼肌细胞胰岛素抵抗的干预作用

目的:研究明日叶查尔酮对2型糖尿病大鼠骨骼肌胰岛素抵抗的干预作用.方法:将2型糖尿病大鼠随机分成四组,高、中、低剂量组分别每日经口灌胃给予明日叶查尔酮30、10和5mg/(kg·bw),糖尿病对照组给予等量生理盐水.各组均以高脂饲料喂养.四周后采用葡萄糖氧化酶法检测空腹血糖;放射免疫法检测血清胰岛素含量;免疫组化法检测葡萄糖转运体1和葡萄糖转运体4蛋白表达水平.结果:经图像分析,高剂量组骨骼肌细胞中葡萄糖转运体1和葡萄糖转运体4蛋白表达平均光密度值分别为0.054± 0.0064和0.063±0.0139,均较糖尿病对照组显著性升高(P＜0.05).高剂量组空腹血糖和胰岛素水平分别为(12.3± 1.64)mmol/L和(25.65±3.34) (μIU/mL),均较糖尿病对照病显著性降低(P＜0.05).结论:明日叶查尔酮可增加2型糖尿病大鼠骨骼肌葡萄糖转运体l和葡萄糖转运体4蛋白表达水平,降低空腹血糖和胰岛素水平,改善胰岛素抵抗状况.     

骨钙素对高糖低脂饮食引起的糖尿病新西兰兔胰腺的影响

目的:基于一贯性高血糖症能导致胰岛素抵抗的假说,我们研究了高糖低脂饮食导致的非胰岛素依赖糖尿病大鼠的生理功能和组织学改变.方法:取正常新西兰兔24只,随机分为正常组、糖尿病(DM)组、糖尿病骨钙素干预(DM+OCGY)组.采用高唐低脂饮食喂养新西兰兔,建立非胰岛素依赖糖尿病模型.建立模型后,DM+OCGY组腹腔注射骨钙素(2.5 mg/kg·d),DM组腹腔注射相等量生理盐水.一个月后处死新西兰兔.用HE染色方法检测新西兰兔胰腺形态改变.结果:高糖低脂饮食能有效引起新西兰兔血糖的升高,尿糖阳性,HE染色表明胰腺细胞发生相应改变,DM+OCGY组空腹血糖的浓度明显降低,能逆转胰腺的相关改变.结论:高糖低脂饮食能诱导非胰岛素依赖糖尿病的发生,骨钙素对非胰岛素依赖型糖尿病血糖浓度有一定的调节作用.     

人脐带间充质干细胞移植对糖尿病大鼠血清学的影响

目的:观察人脐带间充质干细胞(hu MSCs)移植对糖尿病大鼠血糖、胰岛素和血清因子表达的影响。方法:随机选择12只Wistar大鼠通过腹腔注射链脲佐菌素50 mg/kg,血糖高于16.7 mmol/L者定为糖尿病大鼠,再将其随机分为糖尿病组和干细胞组,每组6只,同时选择6只雄性Wistar大鼠为正常组。干细胞组大鼠腹腔注射hu MSCs细胞悬液,糖尿病组注射PBS液。分别于注射2周、4周和6周后测定和比较各组大鼠的血糖、血清胰岛素、肿瘤坏死因子(TNF-α)和白介素-6(IL-6)的表达。结果:与正常组比较,糖尿病组和干细胞组大鼠的血糖水平均显著升高,胰岛素水平均显著降低(P0.01)。与糖尿病组比较,干细胞组大鼠注射hu MSCs后的血糖水平明显降低,胰岛素水平明显升高(P0.05),血清TNF-α和IL-6 m RNA水平均显著降低(P0.01)。结论:hu MSCs移植能显著降低糖尿病大鼠的血糖,促进其胰岛素分泌,同时降低血清TNF-α和IL-6的表达。     

GK糖尿病大鼠生物学特性观察

目的了解2型糖尿病模型GK大鼠生长曲线、主要脏器重量、糖代谢等生物学特性,评价GK大鼠葡萄糖刺激的胰岛素分泌能力。方法采用51只雄性GK大鼠及15只年龄性别匹配的Wistar大鼠作为研究对象。测定13周龄GK、Wistar大鼠空腹血糖、23周龄GK大鼠空腹及随机血糖。随访GK及Wistar大鼠生长曲线,34～46周龄期间血糖、糖化血红蛋白。46周龄时行腹腔葡萄糖耐量实验（IPGTT）,计算相关参数评价β细胞葡萄糖刺激的胰岛素分泌能力;之后处死大鼠,脏器称重。比较GK及Wistar大鼠间上述各指标差异。结果13周龄GK大鼠空腹血糖4．74±0．41mmol／L,对照Wistar大鼠1．85±0．44mmol／L（P〈0．001）。23周龄GK大鼠空腹血糖7．88±1．96mmol／L,随机血糖9．91±3．52～13．46±4．13mmol／L。7～20及34～45周龄期间GK大鼠体重高于对照Wistar大鼠（P〈0．05）,46周龄时无显著性差异。34～45周龄期间GK大鼠空腹血糖、进食后血糖、HbAlc均高于对照Wistar大鼠（P〈0．05）。IPGTT曲线下面积分析示GK大鼠胰岛素曲线下面积（AUCi）、葡萄糖曲线下面积（AUCg）高于对照Wistar大鼠,胰岛素与葡萄糖曲线下面积比值（AUCi／AUCg）低于对照Wistar大鼠,差异均有显著性（P〈0．05）。GK大鼠肾脏重量高于对照Wistar大鼠（P〈0．05）,余主要脏器重量差异无显著性。结论GK大鼠空腹血糖、进食后血糖、HbAlc水平升高,葡萄糖刺激的胰岛素分泌能力（GSIS）减退,葡萄糖刺激后胰岛素分泌早期相消失,晚期相代偿性增加,具有2型糖尿病特点;体重、血糖等生物学特性稳定。     

明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响

目的:研究明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响.方法:将高脂喂养加链脲佐菌素注射诱发的2型糖尿病大鼠随机分为4组,每组10只.糖尿病对照组和高、中、低剂量组喂饲高脂饲料分别经口灌胃明日叶查尔酮0、30、10、5mg (kg·bw)-1,正常对照组为正常大鼠喂饲普通饲料,连续4周.测定空腹血糖、血清胰岛素与MDA、红细胞胰岛素受体结合常数与结合容量等指标.结果:高剂量组的高亲和力与低亲和力胰岛素受体结合常数高于糖尿病对照组,血糖、胰岛素和MDA含量则降低,差异均有显著性(P＜0.05).结论:明日叶查尔酮能提高2型糖尿病大鼠红细胞胰岛素受体亲和力,改善胰岛素抵抗.     

岩藻多糖在2型糖尿病大鼠模型的作用及机制研究

目的:研究岩藻多糖(Fucoidan)对链脲佐菌素诱导实验性2型糖尿病大鼠的治疗作用.方法:在SD大鼠建立2型糖尿病动物模型,随机分为5组,分别用生理盐水、岩藻多糖高、中、低剂量(600mg/kg、400mg/kg、150mg/kg)、二甲双胍(200mg/kg)灌胃给药30天,同时采用正常SD大鼠为正常对照.测定各组大鼠体重、空腹血糖、血脂和血清胰岛素水平.结果:高、中剂量岩藻多糖能够明显降低模型动物空腹血糖水平,降低空腹胰岛素水平,改善胰岛素抵抗,降低血清胆固醇、甘油三酯、低密度脂蛋白胆固醇含量(P<0.05),升高高密度脂蛋白胆固醇含量(P<0.05),其作用效果与阳性对照药二甲双胍效果相当.低剂量岩藻多糖作用效果不明显.结论:岩藻多糖有降血糖、调节血脂紊乱的功能,时实验性2型糖尿病大鼠有治疗作用.     

sGLP-1对Ⅱ型糖尿病大鼠治疗效果的研究

目的 研究人工合成胰高血糖素样截短肽(sGLP-1)对Ⅱ型糖尿病大鼠的治疗效果.方法 Ⅱ型糖尿病GK大鼠随机分为三组,以合成的GLP-1为阳性对照,观察sGLP-1对Ⅱ型糖尿病GK大鼠血糖水平、胰岛素分泌以及糖耐量的影响,通过MTT法测定sGLP-1对胰岛β细胞系β-TC3增殖作用.结果 与GLP-1相比sGLP-1能够长效控制的血糖水平,明显改善糖尿病大鼠的糖耐量(P<0.01).同时sGLP-1能促进胰岛素分泌和胰岛β-TC3细胞的增殖,使得胰岛体积增大,数量增多.结论 sGLP-1控制血糖的长效能力优于GLP-1,可能从刺激胰岛素分泌和促进胰岛β细胞增殖两个方面对Ⅱ型糖尿病具有治疗作用.     

ICAM-1、TG在大鼠糖尿病性下肢溃疡中的意义

目的:研究甘油三脂(TG)、细胞问粘附分子-1(ICAM-1)在糖尿病下肢溃疡大鼠发病中的作用.方法:雄性SD大鼠腹腔注射中等剂量链脲佐菌素(STZ)同时给予高脂饮食建立糖尿病模型;8周末所有大鼠下肢涂抹冰醋酸建立糖尿病下肢溃疡模型,观察溃疡变化;12周末处死大鼠,取血测定空腹血糖、TG、胰岛素、ICAM-1和体重.结果:注射STZ后大鼠出现明显多饮、多尿症状,空腹胰岛素水平明显下降;糖尿病并溃疡组TG、ICAM-1明显高于其他组;而正常对照组与溃疡对照组各项指标无明显差异;TG与ICAM-1两者之间相关性无统计学意义.结论:ICAM-1和TG可能在糖尿病足溃疡的发生中起了重要作用.     

大鼠BTCe对体外培养胰岛保护作用及对糖尿病大鼠降糖作用的研究

β细胞素(betacellulin,BTC)是目前较受关注的胰岛再生因子,但其促胰腺、胰岛再生的机制不清.BTCe是betacellulin的功能片段,促细胞增殖能力与BTC相同.实验通过原核表达方法获得BTCe蛋白,MTT法证实其促3T3-L1细胞增殖能力.将BTC或BTCe作用于原代培养的大鼠胰岛,观察其对胰岛分泌的急性及长期影响作用,实时定量PCR及免疫荧光检测胰岛内关键基因的表达.将质粒pcDNA3.1-BTCe注射入链脲霉素(STZ)诱导的糖尿病大鼠肌肉中,观察对大鼠血糖的影响作用.加入BTC或BTCe可明显提高体外培养大鼠胰岛的GSIS水平,但实时定量PCR及免疫荧光显示胰岛内4种关键基因的表达并无明显变化;pcDNA3.1-BTCe转染糖尿病大鼠15～20天后血糖出现下降,糖耐量明显改善;免疫荧光显示:胰腺内有大量PDX-1 的导管细胞及胰岛素阳性细胞出现.推测BTC及BTCe对体外长期培养的大鼠胰岛具有一定的保护作用,可能通过促进胰腺内PDX-1 的导管细胞及胰岛素阳性细胞的增殖、诱导对STZ诱导的糖尿病大鼠的高血糖具有一定缓解作用.     

体外诱导人羊膜上皮细胞分化为胰岛素分泌细胞的研究

目的:通过体外诱导分化实验,探讨人羊膜上皮细胞(hAECs)向胰岛素分泌细胞(ISCs)分化的能力。方法:采用胰蛋白酶消化法从人羊膜组织分离提取hAECs,用流式细胞仪和免疫细胞化学法进行鉴定。取第3代hAECs在含尼克酰胺和N2补充物的无血清培养基中诱导培养,分别于诱导不同时间采用免疫细胞化学法检测胰岛素和β2微球蛋白的表达,采用放射免疫法检测上清液中胰岛素含量,采用RT-PCR检测胰岛素mRNA和胰十二指肠同源异型盒因子-1(PDX-1)mRNA的表达。结果:①hAECs高表达CD29、CD73、CD166和CK19;②hAECs诱导组第7、142、1天胰岛素阳性细胞百分率分别为74.00%±1.73%、75.33%±1.15%和75.67%±0.58%,而对照组未见胰岛素阳性细胞;③hAECs诱导组第7、14、21天培养物上清液中胰岛素含量分别达(328.47±3.22)μIU/ml、(332.26±1.22)μIU/ml和(329.68±2.57)μIU/ml,均显著高于对照组(P均<0.01);④hAECs诱导前后均有PDX-1 mRNA和β2微球蛋白表达,胰岛素mRNA表达仅见于诱导组。结论:hAECs能分化为ISCs,在Ⅰ型糖尿病细胞移植治疗方面具有潜在应用前景。     

大鼠骨骼肌卫星细胞诱导分化为胰岛素生成细胞的研究

目的探讨大鼠骨骼肌卫星细胞（MDSCs）定向诱导分化为胰岛素生成细胞（IPCs）,为1型糖尿病的干细胞治疗提供一种新的研究思路。 方法通过二次酶消化法和差速贴壁培养法分离、培养大鼠MDSCs,利用不同的诱导培养液使MDSCs定向分化为IPCs,并对诱导后细胞进行形态观察,通过双硫腙染色和免疫组化染色对MDSCs-IPCs形态进行鉴定,采用Q-PCR和Western Blot方法检测MDSCs-IPCs中C-peptide和Insulin的表达,通过胰岛素释放实验检测MDSCs-IPCs的生物学功能,β细胞和MDSCs-IPCs两组间比较采用t检验。 结果MDSCs在接种4 h后开始贴壁部分细胞伸出小的突起,48 h后绝大多数细胞贴壁呈梭形、胞浆丰富、折光度高。随着培养时间的延长,细胞的梭形形状更为明显且生长迅速。免疫组化结果显示细胞表达Desmin、α-Sarcomeric Actinin、MyoD1、Myf5和PAX7。成胰诱导后MDSCs形成胰岛样的圆形细胞团,双硫腙染色呈猩红色,Insulin免疫组化染色阳性。Q-PCR结果显示MDSCs-IPCs中C-peptide和Insulin mRNA表达量分别是β细胞的0.73倍（P > 0.05）和0.79倍（P > 0.05）。胰岛素释放实验显示,5.6 mmol/L和16.7 nmlol/L葡萄糖刺激培养2 h后,β细胞和MDSCs-IPCs分泌胰岛素量分别为[（20.3±4.2）mU/L]、[（16.1±3.7）mU/L]、[（60.5±9.3）mU/L]和[（40.9±7.3）mU/L],葡萄糖可调节MDSCs-IPCs胰岛素的分泌。 结论MDSCs易于分离培养、增殖能力强,体外可诱导分化为有功能的IPCs,适合作为再生医学的种子细胞。     

Resveratrol increases stem cell function in the treatment of damaged pancreas

Pancreatic damage results in insufficient insulin secretion, leading to type 1 diabetes. Stem cell-based therapy has recently shown potential in the treatment of type 1 diabetes. Resveratrol supplementation has demonstrated a beneficial effect in treating diabetes. This study investigates if adipose-derived stem cells (ADSC), preconditioned with resveratrol, show better effects on experimental diabetic animals. Wistar rats were randomly divided into four groups including sham (normal rats), DM (diabetic rats induced by SZT injection), DM+ADSC (DM rats with receiving autologous ADSC transplantation) and DM+R-ADSC (DM rats receiving resveratrol preconditioned ADSC). The experimental results show that SZT induced pancreatic damage (DM group), including reduction of islet size, fibrosis pathway activation, survival signaling suppression, and apoptotic pathway expression, lead to serum glucose elevation. Autologous ADSC (DM+ADSC group) transplantation shows improvement in the above observations in DM rats. Furthermore, ADSC precondition with resveratrol (DM+R-ADSC group) reveals significant improvement in the above pathological observations over both DM and DM+ADSC groups. We found that ADSC precondition with resveratrol increases the survival marker p-Akt expression, leading to enhanced ADSC viability. This study suggests that ADSC precondition with resveratrol shows potential in the treatment of patients with type 1 DM.     

联合应用NGF 和胰岛素对糖尿病大鼠烫伤创面表皮干细胞的影响

目的:通过局部联合应用神经生长因子和胰岛素对糖尿病大鼠深II度烫伤创面表皮干细胞标记物β1整合素和角蛋白19(K19)表达的影响,探讨神经生长因子和胰岛素联合应用于糖尿病烫伤创面治疗后对创面愈合的影响。方法:雄性wistar大鼠腹腔注射链脲佐菌素(STZ)建立糖尿病模型60只,1月后在大鼠背部造成深II度烫伤。将大鼠随机分为糖尿病对照组(B)、胰岛素治疗组(C)、神经生长因子治疗组(D)、神经生长因子联合胰岛素治疗组(E),每组15只。另取15只正常雄性wistar大鼠作为正常对照组(A)。观察伤后3、7、11、15、21 d各组创面愈合情况,检测创面β1整合素和角蛋白19(K19)的表达并计算创面愈合率。结果:E组创面愈合率自第7天起较A、B、C、D组增加,为[(25.33±2.32)%,(P<0.05)];A、C、D组创面愈合率较B组增加分别为[(22.51±1.78)%,(16.68±1.95)%,(18.29±1.70)%,(P<0.05)]。E组整合素β1和角蛋白19(K19)表达自伤后第7至21天各时相点显著增加,(P<0.05)。结论:糖尿病大鼠深II度烫伤创面局部联合应用神经生长因子和胰岛素可促进表皮干细胞的增殖与分化从而加速创面的愈合。     

Insulin-producing cells derived from stem cells: recent progress and future directions

Type 1 diabetes is characterized by the selective destruction of pancreatic beta-cells caused by an autoimmune attack. Type 2 diabetes is a more complex pathology which, in addition to beta-cell loss caused by apoptotic programs, includes beta-cell dedifferentiation and peripheric insulin resistance. beta-Cells are responsible for insulin production, storage and secretion in accordance to the demanding concentrations of glucose and fatty acids. The absence of insulin results in death and therefore diabetic patients require daily injections of the hormone for survival. However, they cannot avoid the appearance of secondary complications affecting the peripheral nerves as well as the eyes, kidneys and cardiovascular system. These afflictions are caused by the fact that external insulin injection does not mimic the tight control that pancreatic-derived insulin secretion exerts on the body's glycemia. Restoration of damaged beta-cells by transplantation from exogenous sources or by endocrine pancreas regeneration would be ideal therapeutic options. In this context, stem cells of both embryonic and adult origin (including beta-cell/islet progenitors) offer some interesting alternatives, taking into account the recent data indicating that these cells could be the building blocks from which insulin secreting cells could be generated in vitro under appropriate culture conditions. Although in many cases insulin-producing cells derived from stem cells have been shown to reverse experimentally induced diabetes in animal models, several concerns need to be solved before finding a definite medical application. These refer mainly to the obtainment of a cell population as similar as possible to pancreatic beta-cells, and to the problems related with the immune compatibility and tumor formation. This review will summarize the different approaches that have been used to obtain insulin-producing cells from embryonic and adult stem cells, and the main problems that hamper the clinical applications of this technology.     

C 肤对糖尿病大鼠坐骨神经结构和功能的影响

目的：探讨外源性C肽对Ⅰ型糖尿病大鼠坐骨神经结构及功能的影响。方法：选取Wistar大鼠40只,分为正常对照组（NC组）和糖尿病组（Dia组）,糖尿病组链脲佐菌素诱发大鼠成模后,再随机分为三组：糖尿病组（Dia组）、胰岛素治疗组（In组）和C肽治疗组（CP组）8周后,测定各组大鼠运动、感觉神经传导速度,并对病变大鼠的坐骨神经进行病理定量图像分析及超微结构分析,结果：1．In组、CP肽组与DM组相比：大鼠运动、感觉神经传导速度均明显增加（P〈0．01）;2．腓肠神经纤维的数量和总横截面面积也显著增加（P〈0.01）。3．CP组与In组相比运动、感觉神经传导速度也显著增加（P〈0．01）。4．电镜显示：Dia组有髓神经纤维髓鞘发生分离并有无颗粒囊胞状结构聚集现象,In组有髓神经纤维髓鞘分离现象明显减轻但仍有无颗粒囊胞状结构聚集现象．而CP组有髓神经纤维结构完全接近正常组。结论：C肽在改善糖尿病大鼠的神经结构和功能方面明显优于胰岛素．     

Protective effects of either C-peptide or l-arginine on pancreatic β-cell function,proliferation, and oxidative stress in streptozotocin-induced diabetic rats

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l -arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1—control nondiabetic, 2—diabetic (no treatment), 3—diabetic + C-peptide, and 4—diabetic + l -arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l -arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l -arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.     

GABA in the endocrine pancreas: cellular localization and function in normal and diabetic rats

Gamma amino butyric acid (GABA) and its related enzymes have been demonstrated in pancreatic beta cells of normal rat. Antibodies against GABA-synthesizing enzymes have been implicated in the pathogenesis of Type I diabetes. In spite of the importance of GABA in the aetiology of diabetes mellitus, detailed morphological data on the pattern of distribution of GABA in the pancreas of normal and diabetic rats are lacking. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (60 mg kg body weight(-1)). Four weeks after the induction of DM, normal (n = 6) and diabetic (n = 6) rats were anesthetized with chloral hydrate and their pancreata were removed and processed for the localization and effect of GABA on insulin secretion using immunohistochemistry and radioimmunoassay techniques. The number of GABA-like immunoreactive (GABA-LIR) cells in the pancreatic islets of STZ-diabetic rats decreased significantly (P<0.0001) when compared to non-diabetic control rats. The pattern and percentage distribution of GABA in the islet of Langerhans of normal and diabetic rat was similar to that of insulin. GABA induced a significant (P<0.0007) increase in insulin secretion from the pancreas of normal rats. In diabetic pancreas, GABA evoked a higher but not significant (P<0.1) increase in insulin secretion. These findings showed that the number of GABA-LIR cells is reduced significantly in diabetes. Moreover, GABA is a strong secretagogue of insulin from the pancreas of normal rat.     

镁补充对2 型糖尿病大鼠糖脂代谢的影响

目的:研究镁补充对2型糖尿病大鼠糖脂代谢的影响。方法:将用高脂饮食联合链脲佐菌素(STZ)方法诱发的2型糖尿病大鼠随机分为四个组,糖尿病对照组喂饲高脂饲料,高、中、低剂量组在高脂饲料中分别加入2000、1000、200 mg/kg的镁(以镁离子计)。自由饮食喂养四周,处死动物。用放射免疫法测血清胰岛素(Ins)水平、用葡萄糖氧化酶法测空腹血浆葡萄糖(fasting plasmaglucose,FPG),并计算胰岛素敏感指数(insulin sensitivity index,ISI)。比色法检测糖化血红蛋白(glycosylated hemoglobin,HbA1c)。用全自动生化分析仪测高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDLC)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)。结果:高剂量组的空腹血糖、空腹血清、糖化血红蛋白、甘油三酯、总胆固醇水平均较糖尿病对照组显著性降低(P<0.05),而高密度脂蛋白胆固醇、胰岛素敏感指数较糖尿病对照组显著性升高(P<0.05)。结论:镁补充可以提高2型糖尿病大鼠胰岛素敏感性,改善糖尿病大鼠的糖脂代谢情况。     

Protection by DHA of Early Hippocampal Changes in Diabetes: Possible Role of CREB and NF-κB

The mechanisms underlying diabetic encephalopathy, are only partially understood. In this study, we try to address the mechanisms of diabetes induced damage and whether docosahexaenoic acid (DHA) could attenuate the degenerative changes in diabetic hippocampus in a rodent model of diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin. Animals were divided into the following experimental groups: control rats; control animals treated with DHA; untreated diabetic rats; diabetic rats treated with insulin; diabetic rats treated with DHA; diabetic rats treated with insulin and DHA. At the end of week 12, rats were killed and one of the hemispheres was cryosectioned and the other was dissected and hippocampi homogenized. The number of bromodeoxyuridine positive cells in the hippocampus of diabetic rats was decreased, and the latency time to find the platform in the Morris Water maze was significantly increased in the diabetic rats when compared to controls. No changes where observed in the expression of p21 in the hippocampus of control and diabetic rats. Biochemical markers of oxidative stress were altered in hippocampus of diabetic rats, and NFκB-positive cells were increased in the hippocampus of diabetic rats when compared to controls. Treatment with DHA, or the combination of DHA with insulin, significantly restored to control levels all the values mentioned above. Our findings confirm a pivotal role for oxidative stress as well as NF-κB, but not p21, in diabetes-induced hippocampal impairments. Administration of DHA as well as insulin prevented the changes induced by diabetes in hippocampus.