葛根素对糖尿病心肌细胞的保护及其机制研究

观察葛根素（Puerarin）对链脲佐菌素（streptozotocin,STZ）诱导的糖尿病大鼠心肌细胞的保护作用,并探讨血小板反应素1（Thrombospondin-1,TSP-1）的表达改变及其作用。雄性SD大鼠45只随机分为三组（n=15）：糖尿病组和葛根素治疗组采用一次腹腔注射链脲佐菌素（STZ）65mg／kg制备糖尿病模型,其中葛根素治疗组于造模后葛根素腹腔注射4周（100mg/kg/day）,正常对照组仅腹腔注射等量生理盐水（6ml／kg）,同样喂养4周。四周后各组大鼠处死。H—E染色及透射电子显微镜观察三组大鼠心肌细胞纤维显微结构和超微结构的病理改变．免疫组化和实时荧光定量PCR法观察大鼠心肌细胞中TSP-1蛋白和mRNA表达的变化．同时利用Langendorff离体心脏灌流法测定各组大鼠心室肌细胞功能。结果发现葛根素治疗组较糖尿病组大鼠的体重增加明显,同时血糖下降,有显著性差异（P〈0．01）。H—E染色显示糖尿病大鼠多处心肌肌丝紊乱伴少量炎症细胞浸润,电镜下发现有线粒体嵴消失溶解,肌丝排列紊乱等病理改变,而葛根素治疗组大鼠偶见上述病理变化。免疫组化显示葛根素治疗组心肌内TSP-1阳性细胞密度小于糖尿病大鼠,TSP-1 mRNA表达也比糖尿病大鼠要低。此外葛根素治疗组大鼠的左室收缩末压（LVSEP）、左心室舒张末期压（LVEDP）等心功能指标均明显低于正常组（P〈0．01）,但较糖尿病组有显著改善（P〈0．01）。上述结果显示葛根素能保护糖尿病大鼠心肌细胞的高糖损伤和维持心室肌细胞的功能,而该机制可能与抑制心肌细胞TSP-1表达的水平有关。     

IL-10基因对糖尿病大鼠胰岛β细胞凋亡的保护作用

目的：研究白细胞介素10（IL-10）基因对链脲佐菌素（STZ）诱导的糖尿病大鼠胰腺炎症浸润程度及胰腺组织中Bcl-2及Bax表达的影响。方法：建立链脲佐茵素性糖尿病模型,腺病毒介导的IL-10基因（Ad-mIL-10）腹腔注射。检测大鼠空腹血糖值;免疫组织化学法观察胰腺炎症浸润程度;TUNEL法检测胰岛细胞凋亡;免疫组化方法观察Ad-mIL-10对实验性糖尿病大鼠胰岛凋亡调控基因Bax和Bcl．2表达的影响。结果：Ad-mlL-10腹腔注射糖尿病发病率低,平均血糖水平低,可以降低胰腺炎症浸润程度,减少胰岛细胞凋亡。给予Ad-mlL-10后大鼠Bax基因的表达明显下降,Bcl-2与Bax的比值明显增加。结论：IL-10基因对实验性糖尿病大鼠有降血糖作用,减少胰岛细胞凋亡,与调节Bcl-2与Bax基因的表达有关。     

姜黄素对糖尿病大鼠大脑海马神经元的作用研究

目的观察姜黄素(Curcumin,Cur)对STZ诱导的2型糖尿病大鼠大脑海马神经元的影响。方法雄性SD大鼠随机分为3组:正常对照组(Con组),高糖高脂饮食结合链脲佐菌素(STZ)诱导的2型糖尿病模型组(DM组)和给予姜黄素处理的糖尿病组(DM+Cur组)。免疫印迹法(WB法)检测大鼠大脑海马凋亡相关蛋白Bcl-2和Bax的蛋白含量;免疫组织化学法(IHC法)检测凋亡执行者caspase-3在大鼠大脑海马各区中的表达情况。结果大鼠给予高糖高脂饮食一个月后,腹腔注射STZ可诱导大鼠血糖升高,继续给予高糖高脂饮食,大鼠出现类似于2型糖尿病的症状,通过WB检测,DM组大鼠海马的Bcl-2/Bax比值较Con组明显下降(P0.05),而给予姜黄素处理16周后的DM+Cur组大鼠可明显增强抗凋亡蛋白Bcl-2的表达而减弱促凋亡蛋白Bax的表达,两者比值增大(P0.05);另外,通过IHC法检测发现,DM组大鼠海马各区的caspase-3阳性表达明显增多,而DM+Cur组可减弱caspase-3的阳性表达。结论高糖高脂饮食结合STZ腹腔注射可诱导出2型糖尿病大鼠模型,姜黄素能通过调控DM大鼠海马凋亡相关蛋白的表达而发挥保护作用。     

IL-10 基因对糖尿病大鼠胰岛beta细胞凋亡的保护作用

目的：研究白细胞介素10（IL-10）基因对链脲佐菌素(STZ)诱导的糖尿病大鼠胰腺炎症浸润程度及胰腺组织中Bcl-2 及Bax 表达的影响。方法：建立链脲佐菌素性糖尿病模型,腺病毒介导的IL-10 基因(Ad-mIL-10)腹腔注射。检测大鼠空腹血糖值;免疫组 织化学法观察胰腺炎症浸润程度;TUNEL法检测胰岛细胞凋亡;免疫组化方法观察Ad-mIL-10 对实验性糖尿病大鼠胰岛凋亡调 控基因Bax 和Bcl-2 表达的影响。结果：Ad-mIL-10 腹腔注射糖尿病发病率低,平均血糖水平低,可以降低胰腺炎症浸润程度,减 少胰岛细胞凋亡。给予Ad-mIL-10 后大鼠Bax 基因的表达明显下降, Bcl-2 与Bax 的比值明显增加。结论：IL-10基因对实验性糖 尿病大鼠有降血糖作用,减少胰岛细胞凋亡,与调节Bcl-2 与Bax 基因的表达有关。     

葛根素对糖尿病致肺损伤的保护作用及其机制的研究

目的:探讨糖尿病对肺脏损伤及葛根素对肺组织影响的可能机制。方法:腹腔注射链脲佐菌素(STZ)建立大鼠糖尿病(DM)模型,SD大鼠随机分为对照组(C组)、糖尿病组(DM组)、糖尿病 葛根素组(DM Pur组)。检测注药前及模型成立后第20d、40d、60d的血糖及体重的改变。检测肺组织中一氧化氮(NO)和丙二醛(MDA)的含量、超氧化物歧化酶(SOD)活性。结合光镜、电镜、免疫组织化学染色方法综合评价。结果:①DM组NO、MDA高于C组(P<0.01),SOD活性低于C组(P<0.01),DM Pur组NO含量明显低于DM组(P<0.01),MDA含量40d开始显著降低(P<0.01),SOD活性高于DM组(P<0.01)。②光镜下见肺泡隔增厚,炎性细胞浸润;电镜下见Ⅱ型肺泡上皮细胞微绒毛数量明显减少,嗜锇性板层小体数量明显减少,细胞间质胶原纤维增生,葛根素可减轻肺组织上述病理性改变。③免疫组织化学染色结果:DM组细胞胞质中可见ONOO-特征性代表物硝基酪氨酸(ni-trotyrosine,NT)黄染阳性信号表达,且较对照组略为增强,DM Pur组黄染信号较DM组略为减弱。结论:①DM时可发生肺组织损伤,可能与长期高血糖诱导产生大量自由基有关。②NO/ONOO-通路是DM造成肺组织细胞损伤的机制之一。③初步证实葛根素能在一定程度上抑制高血糖诱导肺组织中自由基的过量生成,降低肺组织中的ONOO-的过度表达,这可能是其抗DM时肺组织损伤的作用机制之一。     

线粒体介导糖尿病胃平滑肌细胞凋亡的发生

探讨糖尿病胃平滑肌细胞线粒体途径与胃平滑肌细胞凋亡的关系,进一步阐明糖尿病胃轻瘫的相关发病机制。本研究将SD雄性大鼠适应性喂养1周,选择血糖正常鼠40只,随机分为对照组与模型组。造模前禁食12h,自由饮水,模型组大鼠用0．1mmol／L柠檬酸缓冲液配制的2％链脲佐菌素（STZ）60mg／kg一次性腹腔内注射,     

锌和维生素E对Ⅰ型糖尿病大鼠心肌的保护作用

目的探讨锌（Zn）和维生素E（VE）对糖尿病大鼠心肌细胞保护作用的机制。方法按体重将大鼠随机分为正常对照组（10只）和实验组（40只）,实验组动物采用腹腔注射链脲左菌素（streptozotocin,STZ）,60mg/kg一次注射,制备糖尿病大鼠模型。将40只按血糖值参考体重分为4组：糖尿病对照组,糖尿病补锌组,糖尿病补VE组,糖尿病补Zn＋VE组。6周后将各组大鼠处死,切取心室肌组织,进行免疫组织化学染色,观察各组心肌组织NF-κB和i NOS的表达水平,利用HPIAS-2000图像分析系统测定核转录因子（nuclear factor-kappa B,NF-κB）和诱导型一氧化氮合酶（i NOS）在以上各组中表达的平均光密度和平均阳性面积率。结果正常对照组心肌细胞内NF-κB和i NOS呈阴性表达,糖尿病对照组心肌细胞内NF-κB和i NOS呈阳性表达;糖尿病补锌组和糖尿病补VE组心肌细胞内NF-κB和i NOS呈弱阳性表达;糖尿病补Zn＋VE组心肌细胞内NF-κB和i NOS呈阴性表达。图像分析结果显示：糖尿病补Zn＋VE组与糖尿病对照组、糖尿病补锌组及糖尿病补VE组之间NF-κB和i NOS的平均光密度及阳性面积率的差异有显著性意义（P〈0.05）;糖尿病补Zn＋VE组与正常组之间NF-κB和i NOS的平均光密度及阳性面积率的差异无显著性意义（P〉005）。结论Zn和VE联合使用可降低糖尿病大鼠心肌组织中NF-κB和i NOS的活性,对糖尿病大鼠心肌细胞具有保护作用。     

锌和维生素E抑制糖尿病大鼠心肌细胞pDCDS表达

目的探讨锌和维生素E对Ⅰ型糖尿病大鼠心肌TEAR19(TF-cell apoptosis relatedgene 19,PDCDS)基因表达的作用及意义。方法按体重将大鼠随机分为正常对照组(10只)和实验组(40只),实验组动物采用腹腔注射链脲左菌素(streptozotocin,STZ),60mg/kg一次注射,制备糖尿病大鼠模型。将40只按血糖值参考体重分为1:正常对照组;2:糖尿病对照组;3:糖尿病补锌组;4:糖尿病补VE组;5:糖尿病补Zn+VE组。6周后将各组大鼠处死,切取心室肌组织,进行免疫组织化学染色,观察各组心肌组织pDCDS的表达水平,利用HPIAS-2000图像分析系统测定pDCDS在以上各组中表达的平均光密度和平均阳性面积率。结果正常对照组心肌细胞内pDCDS表达呈阴性;糖尿病对照组心肌细胞内pDCDS表达呈阳性;糖尿病补锌组和糖尿病补VE组心肌细胞内pDCDS表达呈弱阳性;糖尿病补Zn+VE组心肌细胞内pDCDS表达呈阴性。图像分析结果显示:糖尿病补Zn+VE组与糖尿病对照组、糖尿病补锌组及糖尿病补VE组之间pDCDS的平均光密度及阳性面积率的差异有显著性意义;糖尿病补Zn+VE组与正常组之间pDCDS的平均光密度及阳性面积率的差异无显著性意义。结论 Zn和VE联合使用可对糖尿病导致大鼠心肌细胞的凋亡具有重要的保护作用。     

米诺环素对糖尿病大鼠视网膜神经细胞凋亡的影响

目的：观察米诺环素对糖尿病大鼠视网膜神经细胞的凋亡的影响,研究米诺环素对糖尿病视网膜神经保护作用,对米诺环素在糖尿病视网膜疾病中抑制神经细胞凋亡提供理论支持。方法：选择健康成年雄性SD大鼠30只,随机分成正常对照组、糖尿病模型组和米诺环素治疗组,每组10只。腹腔内注射链脲佐菌素（STZ）诱发大鼠糖尿病。米诺环素治疗纽给予米诺环素腹腔注射（45mg／kg）,共注射10d,模型组和对照组腹腔注射等体积生理盐水,于给药后8周的3组动物处死,冰浴下取其视网膜组织,随后制备视网膜石蜡切片,采用末端脱氧核糖核酸介导生物素化脱氧尿嘧啶缺口末端标记L（TUNEL）法进行凋亡细胞原位标记,行视网膜神经细胞凋亡计数,对所有数据进行统计学分析。实验结果拟用均数和标准差（x±s）表示,P〈0．05为差异有统计学意义。结果 相同观察时相,与阴性对照组比较,模型对照组大鼠视网膜TUNEL阳性细胞显著增多（P〈0．01）,在米诺环素组,大鼠视网膜TUNEL阳性细胞数比模型对照组明显减少,差异有统计学意义（P〈0．01）。结论：米诺环素能有效降低糖尿病大鼠视网膜神经细胞的凋亡,对糖尿病视网膜神经细胞有保护作用。     

2型糖尿病大鼠心肌损伤时心肌组织中硫氧还蛋白系统的变化

本研究旨在观察2型糖尿病大鼠心肌损伤时硫氧还蛋白(thioredoxin,Trx)系统在心肌组织中的活性变化,并探讨其机制。成年Sprague Dawley大鼠随机分为2组:糖尿病组给予高糖、高脂饮食,并且腹腔注射链唑霉素(streptozocin,STZ)造成大鼠2型糖尿病模型;对照组普通饲料喂养,腹腔注射柠檬酸缓冲液。在注射STZ后不同时间点,测定大鼠血糖浓度和血清胰岛素、肌酸激酶同工酶(creatine kinase MB,CK-MB)、心肌肌钙蛋白I(cardiac troponin I,cTnI)浓度,测定心肌Trx活性、Trx还原酶(thioredoxin reductase,TR)活性和caspase-3活性,用real time PCR和Western blot测定心肌Trx1、Trx2、TR1、TR2和Trx相关蛋白(thioredoxin interacting protein,TXNIP)的mRNA和蛋白表达。结果显示,注射STZ后第1周,2型糖尿病大鼠模型建立成功;注射STZ后第2周即可诱发心肌损伤,第4周上调caspase-3活性。糖尿病组大鼠心肌Trx和TR活性在注射STZ后第2周显著降低,并随病程呈进行性下降;糖尿病组大鼠心肌Trx1、Trx2、TR1、TR2的mRNA水平均在注射STZ后第4周显著下降,而在第12周时则明显升高;Western blot结果显示糖尿病组大鼠心肌Trx、TR、TXNIP蛋白表达在注射STZ后第12周时均显著升高。以上结果表明,2型糖尿病大鼠心肌损伤时Trx和TR活性受抑,而Trx、TR的mRNA表达受到抑制后,代偿性增多,TXNIP的表达明显上调,Trx系统蛋白表达均明显上调,提示Trx系统活性下降的主要原因可能是抑制性蛋白表达升高和化学修饰。     

Puerarin decreases apoptosis of retinal pigment epithelial cells in diabetic rats by reducing peroxynitrite level and iNOS expression

The purpose of this study was to investigate the protective effect of puerarin on retina pigment epithelial (RPE) cells of diabetic rats against apoptosis. One hundred and eight Sprague-Dawley (SD) rats were randomly divided into 3 groups: control group, streptozotocin (STZ) group and puerarin group. STZ and puerarin groups received 3 d of STZ injection (45 mg/kg per day, i.p.). Additionally, puerarin groups were treated with puerarin (140 mg/kg, i.p.) from the 4th day to the end of experiment. The rats from different groups were sacrificed on 20, 40 and 60 d after STZ injection for harvesting RPE cells. Western blot analysis, DNA laddering, RT-PCR and immunohistochemistry were used for determining the expression of nitrotyrosine (NT, the foot print of peroxynitrite), cell apoptosis, iNOS mRNA and Fas/Fas ligand (FasL) signal transduction in RPE cells, respectively. The results showed that control group maintained low apoptosis level and little NT, iNOS mRNA, Fas/FasL protein expressions, as well as normal blood glucose and body weight during 60 d of the experiment. Compared with control group, STZ group showed obvious apoptosis and higher NT, iNOS mRNA, Fas/FasL protein expressions from 20 d after STZ injection. Puerarin relieved apoptosis of RPE cells and decreased NT, iNOS mRNA, Fas/FasL protein expressions in puerarin group 20 or 40 d after STZ injection, compared with STZ group. These results suggest puerarin can decrease RPE cells apoptosis in diabetic rats by reducing peroxynitrite level and iNOS expression, thus being a potential therapeutic agent in controlling of diabetic retinopathy.     

过氧亚硝基阴离子通过JAK/STAT信号途径促进系膜细胞纤连蛋白的合成

氧化应激是糖尿病肾病的重要发病机制之一。过氧亚硝基阴离子(peroxynitrite,ONOO–)是参与氧化应激损伤的重要成员,与糖尿病及其并发症密切相关。该文观察高糖环境下ONOO–对系膜细胞合成纤连蛋白(fibronectin,FN)的影响,并探讨其作用机制。实验中,人肾小球系膜细胞分为4组:正常对照组、高糖组、高糖+尿酸组及高糖+AG490组。培养12,24,48 h后收集细胞及其上清液、并提取细胞总蛋白。采用酶联免疫吸附实验(ELISA)检测细胞上清液中FN的含量,采用免疫细胞化学和Western blot检测NT总蛋白(ONOO–生成的生物标志物)、p-JAK2及p-STAT3蛋白的表达。结果显示,与同期正常组相比,高糖组NT总蛋白、p-JAK2及p-STAT3的表达及FN含量明显增高(P<0.05),并且随着时间的延长表达逐渐增多,以48 h组最为显著;高糖+尿酸组,NT、p-JAK2、p-STAT3及FN较高糖组明显减少(P<0.05);高糖+AG490组,p-JAK2、p-STAT3及FN较高糖组明显减少(P<0.05),但NT表达与高糖组差异无统计学意义(P>0.05)。由此可见,高糖环境下系膜细胞中存在ONOO–的过量表达,ONOO–通过JAK/STAT信号途径促进系膜细胞FN的合成。     

内源性过氧亚硝基阴离子介导脂多糖导致肺动脉内皮细胞损伤

在培养的牛肺动脉内皮细胞(bovine pulmonary artery endothelial cells,BPAECs)水平上,观察脂多糖(lipopolysaccharide,LPS)对BPAECs诱生过氧亚硝基阴离子(peroxynitrite,ONOO~-)能力及内皮源性ONOO~-在LPS致BPAECs损伤中的作用。结果显示:(1)LPS剂量依赖性地引起BPAECs诱生ONOO~-生成标志物硝基酪氨酸(nitrotyrosine,NT)的荧光强度(即ONOO~-)明显增多,NT阳性细胞数和百分率也明显增多或增高(P<0.05);iNOS选择性抑制剂氨基胍(AG)明显抑制LPS诱生ONOO~-增多(P<0.05),而NT阳性细胞数和百分率分别减少或降低,但无明显差异。(2)在LPS作用下BPAECs培养上清中的MDA含量和LDH活性明显增多和增高,呈现剂量依赖性效应。加AG后MDA含量明显降低(P<0.001),LDH活性呈降低趋势。(3)LPS可诱导BPAECs凋亡明显增多,用EB荧光染色后可见细胞染色质浓集、核变小等凋亡征象。AG可导致LPS引起的BPAECs凋亡明显减少,但仍明显高于溶剂组。LPS可导致BPAECs线粒体呼吸抑制及膜电位下降。上述结果表明,LPS可引起BPAECs生成ONOO~-增多,ONOO~-参与介导LPS所致BPAECs过氧化损伤与细胞凋亡。     

Morphological changes in the endocrine pancreas of mice after treatment with streptozotocin combined with cyclophosphamide and neurotropin.

The effect of neurotropin (NSP) in combination with streptozotocin (STZ) and cyclophosphamide (CY) on blood glucose and pancreatic histopathology on day 7 and day 14 after the initiation of the treatment was studied in C57Bl/6 male mice. STZ (40 mg/kg) and NSP (1 mg/kg) were applied intraperitoneally on five consecutive days and CY (150 mg/kg)--twice on day 1 and day 3. In single B cells dilatation of the endoplasmic reticulum was found. On day 7 in proximity to some endocrine cells in the mice treated with STZ, STZ + CY + NSP and STZ + CY macrophages were observed. On day 14 lymphocytic infiltration of the islets was demonstrated only in the groups of mice injected with STZ, STZ + CY while in the group treated with the combination STZ + CY + NSP no infiltration was seen. All experimental groups showed no biochemical evidence for hyperglycemia probably due to the mild destruction of a small number of B cells. The results indicate that NSP might possess a restorative action on insulitis induced by multiple low dose streptozotocin administration in mice.     

Selenium-Vitamin E Combination Modulates Endometrial Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rat

Diabetes mellitus is associated with diabetic impairment of uterine function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. In the present study, the effects of a vitamin E-plus-selenium (VESe) combination on lipid peroxidation (MDA) and the scavenging enzyme activity in the uterine endometrium of streptozotocin (STZ)-induced diabetic rats were investigated. Twenty-four female rats were equally divided into three groups as follows: group I (control); group II (diabetic); group III (diabetic + VESe), STZ + vitamin E (60?mg/kg over 1?day) + selenium-treated (Na2SeO3, 1?mg/kg over 1?day). After 4?weeks of receiving the VESe treatment, endometrium samples were taken from the uterus. Although the VESe treatment decreased the MDA and blood glucose levels in the STZ group, the observed values remained significantly higher than in the controls. Catalase, superoxide dismutase, and glutathione peroxidase activities and body weight gain were significantly (p?<?0.01) lower in STZ groups as compared to control group, whereas their activities were (p?<?0.01) increased by VESe treatment. However, there was no significant difference on body weight gain and uterine weights between control and STZ + VESe groups. In conclusion, the endometrial complications caused by oxidative stress, and the abnormal blood glucose levels in diabetic of rats, can be alleviated by strengthening the physiological antioxidative defense through the administration of vitamin E and Se.     

Autophagy facilitates age-related cell apoptosis—a new insight from senile cataract

Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.Subject terms: Macroautophagy, Apoptosis, Senescence, Diseases     

Nonautonomous apoptosis is triggered by local cell cycle progression during epithelial replacement in Drosophila

Tissue remodeling involves collective cell movement, and cell proliferation and apoptosis are observed in both development and disease. Apoptosis and proliferation are considered to be closely correlated, but little is known about their coordinated regulation in physiological tissue remodeling in vivo. The replacement of larval abdominal epidermis with adult epithelium in Drosophila pupae is a simple model of tissue remodeling. During this process, larval epidermal cells (LECs) undergo apoptosis and are replaced by histoblasts, which are adult precursor cells. By analyzing caspase activation at the single-cell level in living pupae, we found that caspase activation in LECs is induced at the LEC/histoblast boundary, which expands as the LECs die. Manipulating histoblast proliferation at the LEC/histoblast boundary, either genetically or by UV illumination, indicated that local interactions with proliferating histoblasts triggered caspase activation in the boundary LECs. Finally, by monitoring the spatiotemporal dynamics of the S/G₂/M phase in histoblasts in vivo, we found that the transition from S/G₂ phases is necessary to induce nonautonomous LEC apoptosis at the LEC/histoblast boundary. The replacement boundary, formed as caspase activation is regulated locally by cell-cell communication, may drive the dynamic orchestration of cell replacement during tissue remodeling.     

Dietary vitamin C and E modulates oxidative stress induced-kidney and lens injury in diabetic aged male rats through modulating glucose homeostasis and antioxidant systems

Diabetes induces oxidative stress in aged human and rat, although daily supplementation of vitamins C and E (VCE) can be beneficial to aged diabetic rats by reducing free radical production. The aim of the present study was to evaluate whether dietary VCE supplementation relieves oxidative stress in streptozotocin (STZ)-induced diabetic in aged rats. Thirty aged rats were randomly divided into three groups. The first group was used as a control. The second group was made diabetic using a single dose of intraperitoneal STZ. VCE-supplemented feed was given to aged diabetic rats constituting the third group. On the 21st day of the experiment, blood, lens and kidney samples were taken from all animals. Glutathione peroxidase (GSH-Px) activity in lens and kidney, reduced glutathione (GSH), vitamin E and β-carotene concentrations in kidney were lower in the diabetic group than in the control whereas plasma glucose, urea and creatinine, and kidney and lens peroxidation (LP) levels were higher in the diabetic group than in the control. However, kidney and lens LP levels, and plasma glucose, urea and creatinine values were decreased by VCE supplementation. Lens and kidney GSH-Px activity, kidney GSH, vitamin E and β-carotene concentrations and erythrocyte counts were increased by VCE treatment. Kidney weights, vitamin A, haemoglobin, hematocrit, leukocyte and platelets values were not changed by diabetes and/or VCE supplementation. VCE ameliorated also diabetes-induced histopathological changes in kidney. In conclusion, we observed that VCE supplementation is beneficial towards kidney and lens of aged diabetic rats by modulating oxidative and antioxidant systems.