Oxidative stress in kidney and liver of alloxan-induced diabetic rabbits: effect of repaglinide

Abstract The aim of this study was to analyse the effect of the new oral antidiabetic drug repaglinide on antioxidant factors and lipid peroxidation in tissues of alloxan-induced diabetic rabbits after 4 and 8 weeks treatment. The activity of superoxide dismutase (diabetic vs. control values, mean±S.E.M., p<0.05) in diabetic kidney was diminished (1.5±0.2 vs. 2.8±0.3 and 1.8±0.1 vs. 2.9±0.3 U/mg protein) and significantly increased after 8 weeks of repaglinide treatment (2.4±0.2 U/mg protein). Catalase activity was significantly increased in diabetic liver (67.5±3.6 vs. 39.7±5.6 and 62.3±2.7 vs. 52.6±5.3 µmol H₂O₂/min/mg protein) and normalised by repaglinide (49.2±4.0 and 41.2±3.8 µmol H₂O₂/min/mg protein). In diabetic kidney the level of ascorbic acid was diminished after 4 weeks (1.5±0.1 vs. 3.0±0.1 µmol/g tissue) and increased after the drug treatment (2.0±0.2 µmol/g tissue). In diabetic kidney the level of lipid peroxidation products was elevated (33.3±2.4 vs. 23.7±2.4 and 29.5±3.1 vs. 18.2±0.8 nmol/g tissue) and diminished by repaglinide (10.3±1.4 and 13.3±3.0 nmol/g tissue). This study shows that oxidative stress in diabetic tissues is partly corrected by repaglinide. The drug does not affect glucose concentration and its antioxidative effect is not secondary to its action on hyperglycaemia. This study suggests an additional advantage of repaglinide which contributes to its effectiveness in therapy.     

砷和香烟烟气溶液对氧化应激的协同作用

目的研究亚砷酸钠和香烟烟气溶液联合作用对大鼠淋巴细胞氧化应激的影响，并探讨两者对氧化应激的影响是否存在交互作用。方法大鼠淋巴细胞分为4组：亚砷酸钠单独作用组、香烟烟气溶液单独作用组、两者联合作用组和对照组，染毒后用流式细胞术检测细胞内活性氧的含量，用微量荧光法检测细胞内丙二醛含量，用彗星实验检测细胞的DNA损伤，同时采用2×2析因设计研究两者的交互作用。结果亚砷酸钠单独作用组、香烟烟气溶液单独作用组和两者联合作用组细胞内的活性氧含量、丙二醛含量、彗星尾长和细胞拖尾率均高于对照组。析因设计分析结果表明两者对细胞内活性氧含量、丙二醛含量及彗星尾长的影响存在交互作用。结论亚砷酸钠和香烟烟气溶液对大鼠淋巴细胞氧化应激的影响存在交互作用，交互作用方式为协同作用。     

二甲双胍联合利拉鲁肽对棕榈酸诱导的内皮细胞氧化损伤具有协同保护作用

目的 探讨二甲双胍和利拉鲁肽在改善棕榈酸诱导的人脐静脉内皮细胞氧化损伤方面是否具有协同保护效应.方法 分离培养人脐静脉内皮细胞,应用不同浓度棕榈酸处理诱导细胞氧化损伤,观察不同浓度二甲双胍和（或）利拉鲁肽对细胞氧化损伤的影响.流式细胞仪检测细胞内的活性氧簇（ROS）水平,硝酸还原酶法检测上清一氧化氮（NO）的水平,组间比较采用单因素方差分析和Q检验.结果 与对照组相比,0.25和0.50 mmoL/L棕榈酸细胞内ROS水平显著升高[（125±17）％、（189±8）％比100％,P＜0.05],上清NO水平降低[（89.9±6.2）％、（79.8±4.8）％比100.0％,P＜0.05];二甲双胍（0.5 ～ 1.0 mmol/L）和利拉鲁肽（10 ～ 100 nmol/L）单独应用后,可使0.50 mmol/L棕榈酸所致的ROS产生增加和NO产生减低作用下降;低剂量的二甲双胍（0.1 mmol/L）或利拉鲁肽（3 nmoL/L）单独应用对0.5 mmol/L棕榈酸的作用均无明显的影响,但两者联合则可减低上述作用：两者联合组与棕榈酸组相比,ROS水平降低[（158±31）％比（250±27）％,P＜0.05],NO水平增加[（91.7±30.6）％比（82.3±5.0）％,P＜0.05].结论 二甲双胍和利拉鲁肽在改善棕榈酸诱导的内皮细胞氧化损伤方面具有协同效应.     

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle

OBJECTIVE:

To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation) and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively]) in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS) for 7, 15, 30, 45, or 60 days.

METHODS:

Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group): a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively.

RESULTS:

Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice), the greatest differences (increases) in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases) in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle.

CONCLUSION:

Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily) in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.     

别嘌呤醇对高糖诱导损伤的人脐静脉血管内皮细胞的保护作用

目的探讨别嘌呤醇对高糖损伤后的人脐静脉血管内皮细胞（HUVEC）的保护作用及其机制。方法以HUVEC为研究对象,体外培养至第三代,分为：①20mmol／L高糖损伤对照组;②别嘌呤醇保护组（浓度分别为0．1mmol／L、0．2mmol／L、0．3mmol／L）;③维生素C阳性对照组（浓度为100mg／L）。不同浓度别嘌呤醇及维生素C先与HUVEC孵育24h,再加入20mmol／L高糖诱导损伤48h,测定各组细胞上清液中一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）、细胞间黏附分子-1（ICAM-1）含量及细胞凋亡率。结果别嘌呤醇（0．1mmol／L、0．2mmol／L、0．3mmol／L）药物保护组的细胞凋亡率低于20mmol／L高糖组,其中以0．3mmol／L更为明显（P〈0．01）;细胞培养液中SOD、NO的量均较20mmol／L高糖组增高,其中以0．3mmd／L别嘌呤醇组更为明显（P〈0．01）。药物保护组细胞培养液中合成MDA、ICAM-1较波动性高糖组降低,且在一定浓度范围内（0．05-49．30mmol／L）呈浓度依赖性（P〈0．05）。结论①别嘌呤醇对高糖体外诱导的HUVEC损伤有保护作用,呈浓度依赖性。②别嘌呤醇对高糖体外诱导HUVEC损伤保护作用的机制包括抑制氧化应激、炎症反应及细胞凋亡。     

银杏叶提取物对老龄大鼠心肌保护作用的研究

目的 探讨银杏叶提取物对老龄大鼠心肌的保护作用.方法 选择20月龄大鼠,分别给予银杏叶提取物(EGB)和非酶糖基化产物(AGEs)交联结裂解剂(ALT-711)灌胃,经16周治疗后,观察心肌内AGEs、血清内抗氧化活性物质超氧化物歧化酶(SOD)和谷胱甘肽过氧化酶(GSH-Px)及氧化代谢产物丙二醛(MDA)的含量,观察心肌细胞内线粒体DNA的缺失率及心肌超微结构的改变.结果 老龄对照组大鼠和成年对照组比较.心肌细胞间质增生、肿大,线粒体和内质网膜受损,心肌组织内AGEs含量减少[分别为(33.5±1.3)AU/mgHYP和(18.1±1I 2)AU/mgHYP,t=7.18,P<0.05],血清中SOD和GSH-PX减少[分别为(138.4±3.8)U/ml和(1283.8±28.8)U/ml、(227.7±13.8)U/ml和(2114.1±135.9)U/ml,t分别为-19.59和-18.79,均P<0.01],MDA增多[分别为(6.7±0.6)mmol/ml与(4.1±1.O)mmol/ml,t=7.18,P<0.05],线粒体mtDNA缺失率增多[(0.1805±0.0718)%和(0.0060±0.0001)%,t=6.98,P<0.01],EGB和ALT-711治疗组与老年对照组比较,心肌内AGEs产物减少(P<0.05).血清内SOD、GSH-PX抗氧化物质增多(P<0.05),血清氧化代谢产物MDA减少(P<0.05),mtDNA缺失率减少(P<0.01).结论 老龄大鼠心肌老化和非酶糖基化及氧化应激相关,EGB和ALT-711同样具有抑制非酶糖基化和抑制氧化应激的作用,通过对心肌内线粒体mtDNA缺失率的抑制,具有抗衰老作用.     

人心肌热休克蛋白27基因克隆及其高表达对大鼠心肌细胞氧化损伤的保护作用

目的克隆和重组人心肌热休克蛋白27(HSP27)基因,观察HSP27高表达对大鼠心肌细胞氧化应激的影响。方法将RTPCR获得的人心肌HSP27基因全长cDNA,重组入质粒载体pCDNA31 。将重组体pCDNA31 /HSP27转染大鼠心肌细胞系H9c2,经G418选择性培养获得稳定转染细胞系;观察HSP27高表达对H2O2诱导的乳酸脱氢酶(LDH)释放和细胞凋亡的影响。结果(1)pCDNA31 /HSP27在293T和H9c2中表达良好;(2)0、100、250、500、1000μmol/LH2O2引起的LDH释放,在HSP27高表达组和野生型组分别为0396±0017和0390±0009、0437±0014和0416±0015、0471±0018和0417±0009、0505±0030和0657±0022、0547±0027和0661±0011(均为P<0001);(3)150μmol/LH2O2诱导的细胞凋亡在HSP27高表达和野生型组分别为总细胞数的(10693±1122)%和(4027±1628)%,P<001。结论人心肌HSP27基因被成功克隆和重组,其在大鼠心肌细胞系H9c2的高度表达显著保护了该细胞的过氧化损伤。     

DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes

AIM:To study the effect of fluoride on oxidative stress,DNA damage and apoptosis as well as cell cycle of ratoral mucosal cells and hepatocytes.METHODS:Ten male SD rats weighing 80～120 g wererandomly divided into control group and fluoride group,5 animals each group.The animals in fluoride group hadfree access to deionized water containing 150 mg/L so-dium fluoride(NaF).The animals in control group weregiven distilled water.Four weeks later,the animals werekilled.Reactive oxygen species(ROS)in oral mucosa andliver were measured by Fenton reaction,lipid peroxida-tion product,malondialdehyde(MDA),was detected bythiobarbituric acid(TBA)reaction,reduced glutathione(GSH)was assayed by dithionitrobenzoic acid(DTNB)reaction.DNA damage in oral mucosal cells and hepa-tocytes was determined by single cell gel(SCG)electro-phoresis or comet assay.Apoptosis and cell cycle in oralmucosal cells and hepatocytes were detected by flowcytometry.RESULTS:The contents of ROS and MDA in oral mucosaand liver tissue of fluoride group were significantly high-er than those of control group(P<0.01),but the level ofGSH was markedly decreased(P<0.01).The contents ofROS,MDA and GSH were(134.73±12.63) U/mg protein,(1.48±0.13)mmol/mg protein and(76.38±6.71)mmol/mg protein in oral mucosa respectively,and(143.45±11.76)U/mg protein,(1.444-0.12)mmol/mg protein and(78.83±7.72)mmol/mg protein in liver tissue respective-ly.The DNA damage rate in fluoride group was 50.20%in oral mucosal cells and 44.80% in hepatocytes,higherthan those in the control group(P<0.01).The apop-tosis rate in oral mucosal cells was(13.63±1.81)% influoride group,and(12.76±1.67)% in hepatocytes,higher than those in control group.Excess fluoride coulddifferently lower the number of oral mucosal cells andhepatocytes at G_0/G_1 and S G_2/M phases(P<0.05).CONCLUSION:Excess fluoride can induce oxidative stress and DNA damage and lead to apoptosis and cellcycle change in rat oral mucosal cells and hepatocytes.     

糖尿病中的氧化损伤与抗氧化研究进展

活性氧簇(ROS)引起的氧化损伤在糖尿病并发症的发病机制中起重要作用,最新研究显示线粒体ROS增加可能是糖尿病并发症发病的共同基础。ROS催化脂质、蛋白质／氨基酸及DNA 所形成的某些化学性质相对稳定的产物,有望成为反映氧化损伤的理想生物标志。近来发现噻唑烷二酮类药物、瑞格列奈、他汀类药物、血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂和钙通道阻滞剂兼有较强的抗氧化活性,有助于防治糖尿病并发症。     

Role of Oxidative Stress in Celecoxib-Induced Renal Damage in Wistar Rats

Celecoxib, a selective cyclo-oxygenase-2 (Cox-2) inhibitor, prevents the formation of prostaglandins, responsible for maintenance of renal function. Celecoxib administration may lead to renal damage. Since free radicals and antioxidant mechanisms play a significant role in renal injury; this study was designed to evaluate the role of oxidative stress in celecoxib-induced renal damage. The administration of celecoxib resulted in moderate and mild tubulointerstitial nephritis in chronic and acute group. The renal function tests were significantly altered only in the chronic group. The results in both the acute and the chronic group showed (1) a significant increase in the lipid peroxidation and in the activities of superoxide dismutase, catalase and glutathione-S-transferase and (2) a decrease in nitrite, reactive thiols and glutathione. In conclusion, our study suggests that chronic administration of celecoxib may have a damaging effect on kidney, as evident through altered histopathology and renal functions. This damage may be mediated by oxidative stress.     

棓丙酯对高糖诱导人肾小管上皮细胞损伤的保护作用

目的 观察樯丙酯对高糖诱导人肾小管上皮细胞损伤的保护作用.方法 传代培养人肾小管上皮细胞（HK-2）,分为对照组、高渗组、高糖组、处理组1（桔丙酯浓度2μg/ml）和处理组2（棓丙酯浓度4μg/ml）,观察各组细胞增殖能力、凋亡率、活性氧（ROS）水平以及bcl-2和BaxmRNA的表达情况.结果 高糖刺激HK-2细胞后,细胞增殖能力下降、凋亡增加、ROS水平升高、bcl-2 mRNA表达减少、Bax mRNA表达增多.棓丙酯可以提高细胞增殖能力,减少凋亡,降低ROS水平,上调bcl-2 mRNA表达以及下调BaxmRNA表达;处理组2上述改变较处理组1明显（P均＜0.05）.结论 桔丙酯改善高糖诱导的人肾小管上皮细胞损伤,其机制可能与减轻氧化应激、上调bcl-2 mRNA表达以及下调Bax mRNA表达有关.     

α-硫辛酸降低糖尿病大鼠肾脏氧化应激水平

将大鼠分成正常对照（NC）组、糖尿病（DM）组及糖尿病加α-硫辛酸（DM＋ALA）组进行实验。4周后DM组24小时尿白蛋白（UAlb/24h）、肾重/体重（KW/BW）和丙二醛（MDA）含量均较NC组增加，总超氧化物歧化酶（TSOD）活性降低，谷胱甘肽过氧化物酶（GSH-Px）活性升高，过氧化氢酶（CAT）活性无变化；DM＋ALA组较DM组UAlb/24h、KW/BW和MDA水平降低，TSOD、GSH-Px和CAT活性无改变。结果说明，ALA能减低DM大鼠肾皮质氧化应激水平，延缓糖尿病肾病进展。     

Oxidative injury in rat fatty liver exposed to ischemia-reperfusion is modulated by nutritional status

BACKGROUND AND AIMS: Oxidative stress contributes to ischemia-reperfusion injury in fatty livers. This study aimed to determine whether glycogen depletion influences this oxidative injury and whether the administration of glucose can be protective. METHODS: Rats with choline deficiency-induced fatty liver underwent hepatic ischemia-reperfusion. Experimental groups: (1) fed rats; (2) 18 h fasted rats; (3) 18 h fasted rats supplemented with glucose prior to surgery. The thiobarbituric acid-reactive substances, protein carbonyls and total glutathione concentrations were measured in liver tissue and isolated mitochondria as parameters of oxidative stress before and after ischemia and during reperfusion. The mitochondrial F1-ATPase content and the serum alanine transaminase were also determined. RESULTS: With respect to fed rats, fasted rats exhibited an increased oxidative injury in both liver tissue and isolated mitochondria throughout the experiment with the only exception of thiobarbituric acid-reactive substances, which were not affected by the nutritional status in liver tissue. Fasted rats showed a significantly lower F1-ATPase content and higher alanine transaminase levels. Glucose supplementation significantly reduced the fasting-associated exacerbation of oxidative stress and liver injury and the F1-ATPase exhaustion. CONCLUSIONS: These data indicate that the pre-existing hepatic glycogen content modulates the oxidative damage in rat fatty livers exposed to ischemia-reperfusion injury and that the energetic substrate supplementation may represent a clinically feasible protective strategy.     

Vitamin E attenuates alcohol-induced aortic wall damage in rats

BackgroundIn this study the effect of chronic ethanol consumption on vascular wall abnormality via oxidative stress was examined. It was also intended to find out whether vitamin E inhibits the abnormality induced by ethanol in rat vascular wall.MethodsTwenty-four male wistar rats were divided into three groups, namely, control, ethanol (4.5 g/kgBW intragastrically), and vitamin E treated ethanolic groups(VETE) (300 mg interagastrically).ResultsAfter 6 weeks treatment of rats, the results revealed that along with a significant increase VSMC proliferation and aorta wall thickness with the increase in the level of Ox-LDL, protein carbonyl, as well as decrease total antioxidant capacity in animal that received ethanol compared to the control group. Significant amelioration of aorta wall changes, along restoration of the elevated level of Ox-LDL, protein carbonyl, lipid profile, and decreased level of total antioxidant capacity to that of controls were found in vitamin E-treated animals.ConclusionsThese findings strongly support the idea that heavy and chronic ethanol consumption initiate atherosclerosis by oxidative stress, and that these effects can be alleviated by vitamin E as an antioxidant.     

N-acetylcysteine attenuates renal alterations induced by senescence in the rat

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on sodium and water transporters, in the kidneys of aged rats. Normal, 8-month-old male Wistar rats were treated (n = 6) or not (n = 6) with NAC (600 mg/L in drinking water) and followed for 16 months. At the end of the follow-up period, we determined inulin clearance, serum thiobarbituric acid reactive substances (TBARS), serum cholesterol, and urinary phosphate excretion. In addition, we performed immunohistochemical staining for p53 and for ED-1-positive cells (macrophages/monocytes), together with Western blotting of kidney tissue for NKCC2, aquaporin 2 (AQP2), urea transporter A1 (UT-A1) and Klotho protein. At baseline, the two groups were similar in terms of creatinine clearance, proteinuria, cholesterol, and TBARS. At the end of the follow-up period, NAC-treated rats presented greater inulin clearance and reduced proteinuria, as well as lower serum cholesterol, serum TBARS, and urinary phosphate excretion, in comparison with untreated rats. In addition, NAC-treated rats showed upregulated expression of NKCC2, AQP2, and UT-A1; elevated Klotho protein expression, low p53 expression, and few ED-1 positive cells. In conclusion, we attribute these beneficial effects of NAC (the significant improvements in inulin clearance and in the expression of NKCC2, AQP2, and UT-A1) to its ability to decrease oxidative stress, inhibit p53 expression, minimize kidney inflammation, and stimulate Klotho expression.     

Oxidative phosphorylation and respiration by mitochondria from normal, hypertrophied and failing rat hearts.

The present study was undertaken in order to determine the differences in mitochondrial respiration and oxidative phosphorylation of the myocardium from rats with monocrotaline pyrrole induced pulmonary heart disease. Experimental animals developed right ventricular hypertrophy and heart failure 6 weeks post monocrotaline pyrrole injection. Respiratory function of heart mitochondria in glutamate and succinate substrates was evaluated polarographically. Mitochondrial electron transport and phosphorylating efficiency increased slightly during cardiac hypertrophy, began to decline during impending cardiac failure, and was markedly impaired in congestive heart failure.     

褪黑素对心肌细胞氧化损伤保护作用的实验研究

目的　探讨氧化损伤时褪黑素 (MT)对心肌细胞形态学变化、细胞存活率、自身一氧化氮 (NO)生成的影响 ,以及NO水平与其它氧化指标的关系。方法　分离培养原代心肌细胞 ,分为对照组、H2 O2 处理组、MT组、MT干预组和N 硝基 L 精氨酸 (L NAME)干预组五组进行对照。用外源性H2 O2 造成氧化损伤 ,用生化法检测培养液中乳酸脱氢酶 (LDH)浓度 ,台盼蓝排斥试验检测细胞存活率 ,硫代巴比妥酸法检测细胞中丙二醛 (MDA)含量 ,用试剂盒检测细胞培养液中NO含量。结果　H2 O2 处理组和L NAME干预组中的细胞存活率、NO含量、LDH含量和MDA含量与对照组比较差异有非常显著性 (P <0 .0 1) ,H2 O2 处理组四项均比对照组明显增高 ,而L NAME干预组中NO含量比对照组明显低。MT干预组与L NAME干预组比较LDH含量和MDA含量明显低 (P <0 .0 1) ,与H2 O2 组加入MT干预后 ,培养液中NO和LDH及MDA含量明显降低 (P <0 .0 1)。结论　心肌细胞在受到H2 O2 损伤时 ,心肌细胞自身产生的NO增加 ,并且在一定程度上参与了对心肌细胞的氧化损伤 ;MT不仅能抑制LDH和MDA的升高 ,还能抑制NO的产生。     

投氟大鼠肾组织蛋白质组学的初步研究

目的探讨蛋白质组学技术在投氟所致大鼠肾组织蛋白质的整体表达变化研究中的价值，为氟中毒肾损害机制的研究提供新途径。方法采用固相pH梯度（IPG）等电聚焦双向凝胶电泳方法，对投氟（100mg／L）8周和对照大鼠肾组织的蛋白质进行分离，使用Image master 2Delite图像软件分析电泳图谱．利用基质辅助激光解吸电离-飞行时间质谱仪对两组间比较具有统计学有意义的差异蛋白点进行鉴定。结果在对照组大鼠肾组织蛋白双向电泳图谱上可观察到624个蛋白点．而投氟组肾组织双向电泳图谱上可见到776个蛋白点。与对照组比较，在投氟组大鼠肾组织表达明显改变的蛋白点经质谱鉴定出13种，主要是与细胞代谢、增殖和氧化应激相关的蛋白，其中11种蛋白表达增多，2种降低。结论本实验所采用的双向电泳和质谱鉴定方法可有效分离和分析肾整体蛋白点，并反映出投氟大鼠肾组织细胞代谢旺盛、增殖活跃和氧化应激明显的特点．表明蛋白质组学技术在氟中毒肾损害研究中具有实用价值。     

内质网及氧化应激在大鼠慢性肝损伤中的变化

目的研究内质网应激相关基因、氧化应激指标在四氯化碳诱导的大鼠慢性肝损伤中的变化。方法四氯化碳制备大鼠慢性肝损伤模型,通过测定大鼠血清ALT、AST水平,采用HE染色和TUNEL法观察肝组织病理形态和肝细胞凋亡改变,评价成模效果。检测大鼠肝脏葡萄糖调节蛋白78（GRP78）、GRP94、血红素加氧酶（HO）-1 mRNA表达及超氧化物歧化酶（SOD）、丙二醛（MDA）、还原型谷胱甘肽（GSH）变化。结果四氯化碳成功诱导了大鼠慢性肝损伤,与对照组相比,大鼠肝脏GRP78、GRP94、HO—1的表达量、MDA含量均明显增加,SOD活性、还原型GSH显著降低。结论四氯化碳诱导大鼠慢性肝损伤时,内质网应激相关基因的表达增加,氧化应激指标亦发生改变,表明内质网应激、氧化应激共同参与了大鼠慢性肝损伤过程。     

茶多酚对饮茶型氟中毒大鼠关节软骨氧化损伤的保护作用

目的 探讨茶多酚对饮茶型氟中毒大鼠关节软骨的氧化应激损伤的保护作用.方法 120只雄性Wistar大鼠按体质量随机分为6组:对照组、加氟组、氟+茶多酚组、氟+铝组、氟+铝+茶多酚组和砖茶组.加氟组每日饮用含氟(F-)100.00 mg/L的氟化钠(NaF)水溶液;氟+茶多酚组每日饮用含F-100 mg/L、茶多酚10.0 g/L的水溶液;氟+铝组每日饮用含F-100.00 mg/L、铝(Al3+)200.00 mg/L的水溶液;氟+铝+茶多酚组同时饮用含有上述3种物质的水溶液:砖茶组饮用砖茶沏制而成的砖茶水(F- 100.00 mg/L、Al3+215.00mg/L、9.2 g/L);对照组饮用自来水(F- 0.33 mg/L).连续饲养3个月,处死动物,检测血清中超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)、戊二醛(MDA)、一氧化氮(NO)和细胞因子白介素1β(IL-1β)、白介素6(IL-6)的水平;RT-PCR和免疫组化法检测关节软骨中诱生型一氧化氮合酶(iNOS)mRNA及蛋白表达.结果 氟 +铝+茶多酚组SOD水平[(664.009±29.589)kU/L]与加氟组、氟+销组[(625.328±27.199)、(652.282±13.926)kU/L]比较有升高趋势,但是差异无统计学意义(P均>0.05);氟+茶多酚组、氟+铝+茶多酚组、砖茶组T-AOC水平[(10.874±0.721)、(11.871±0.941)、(10.380±2.747)kU/L]与加氟组、氟+铝组[(8.849±1.887)(8.210±1.740)kU/L]比较,差异有统计学意义(P均<0.05);氟+铝+茶多酚组血清中MDA水平[(3.235±0.446)μmol/L]与加氟组、氟+铝组[(3.889±0.387)、(4.580±0.474)μmol/L]比较,差异有统计学意义(P均<0.05);氟+茶多酚组、氟+铝+茶多酚组、砖茶组血清中NO水平[(23.278±2.386),(20.643±2.623)、(24.367±6.072)μmol/L]与加氟组、氟+铝组[(32μ962±8.268)、(34.909±6.288)μmol/L]比较,差异有统计学意义(P均<0.05):加氟组、氟+销组、氟+茶多酚组、氟+铝+茶多酚组、砖茶组血清IL-1β水平分别为(4.728±0.297)、(4.412±0.229)、(4.432±0.285)、(4.516±0.351)、(4.614±0.2270)ng/L,组间比较,差异无统计学意义(F=2.314,P>0.05);氟+铝+茶多酚组、砖茶组IL-6水平[(7.231±0.596)、(7.325±0.290)ng/L]与氟+铝组[(8.256±0.635)ng/L]比较,差异有统计学意义(P均<0.05).氟+茶多酚组、氟+铝+茶多酚组、砖茶组iNOS mRNA相对表达量(0.482±0.021、0.447±0.021、0.491±0.022)与加氟组、氟+铝组(0.562±0.025、0.591±0.020)比较,差异有统计学意义(P均<0.05);对照组iNOS蛋白表达阳性细胞主要分布在关节表层,各实验组iNOS阳性细胞在关节面表层、中层均有分布.结论 茶多酚能通过清除氧自由基、提高机体总抗氧化能力、减少脂质过氧化产物等抗氧化作用减轻饮茶型氟中毒引起的大鼠氧化应激损伤,对饮茶型氟中毒有一定的保护作用.