姜黄素对糖尿病大鼠心肌的保护作用*

 目的： 研究姜黄素对糖尿病大鼠心肌的保护作用及可能机制。方法: 雄性Wistar大鼠75只,随机抽取10只大鼠作为正常对照组,其余65只大鼠给予高糖高脂饮食喂养8周后腹腔注射链脲佐菌素40 mg/kg,给药72 h和7 d空腹血糖≥11.6 mmol/L为糖尿病模型成功大鼠。糖尿病大鼠随机分为糖尿病心肌病组、姜黄素小剂量治疗组和大剂量治疗组。测定心肌谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）含量,酶联免疫吸附试验检测血清心肌钙蛋白I（cTnI）的变化,Western blotting检测蛋白激酶C（PKC）蛋白表达。结果: 姜黄素治疗后可明显改善糖尿病所致的动物体重下降和空腹血糖升高,抑制心肌中MDA的产生并升高GSH-Px活性,减少血清中cTnI的释放,下调心肌组织PKC蛋白表达。结论: 姜黄素对大鼠糖尿病心肌病具有保护作用,其机制可能与抑制氧化应激有关。     

Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the livers of male Wistar rats

Glutathione-S-transferases and glutathione play a key role in the detoxification of most toxic agents. In the present study, the protective effects, if any, of isoflavone phytoestrogens--genistein and daidzein on the carbon tetrachloride (CCl4) induced changes in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S transferase (GSH) and levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)-were studied. The activities of ALT and AST were assayed in the serum, whereas the activity of GST and levels of GSH and TBARS were determined in the livers of rats. The current study involved the division of animals into two main groups: (i) rats pretreated with genistein and daidzein for three days; and (ii) non-pretreated rats. In the pretreated group, rats received oral doses of genistein (7.9 micromol/kg body weight) and daidzein (7.9 micromol/kg body weight) for three consecutive days (once daily) followed by oral dose of CCl4 on the 4th and the 5th day concurrently with the phytoestrogens-genistein or daidzein. In the non-pretreated group animals received oral dose of CCl4 (1 ml/kg body weight) for two consecutive days along with the phytoestrogens-genistein or daidzein. Treatment of male rats with CCl4 significantly elevated the activity of ALT and AST in serum and levels of TBARS in the liver. On the other hand, CCl4 resulted in decreased activity of GST and lowered the GSH levels. Coadministration of genistein and daidzein with CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to normal control levels. However, repeated dose treatments with genistein and daidzein for three days prior to the administration of CCl4 restored such alterations to normal levels. Our results indicate that genistein is more effective than daidzein in counteracting the inhibition of GST activity caused by CCl4 and restoring it to normal levels. Genistein was also more effective than daidzein restoring the induced TBARS levels caused by CCl4 to normal control levels when rats were pretreated with the isoflavone orally for three days. It has been observed that the tested isoflavonoids were able to antagonize the toxic effects of CCl4. Such counteracting effects were more pronounced for genistein and when the phytoestrogens were administered as repeated doses prior CCl4 administration.     

红景天苷通过抑制氧化应激防治大鼠低氧性肺动脉高压

目的:观察低氧性肺动脉高压大鼠肺组织及血清中氧化/抗氧化相关指标的变化,研究红景天苷(Sal)能否通过恢复氧化/抗氧化系统平衡防治低氧性肺动脉高压。方法:将32只SD大鼠随机分为4组:常氧(normoxia,N)组、低氧4周(hypoxia for 4 weeks,H_4)组、Sal低剂量(hypoxia for 4 weeks and treatment with Sal at 16mg/kg,H_4S16)组和Sal高剂量(hypoxia for 4 weeks and treatment with Sal at 32 mg/kg,H_4S32)组。造模完成后测定平均肺动脉压(m PAP)、右心室/(左心室+室间隔)[RV/(LV+S)]和血管壁面积/血管总面积(WA/TA);测量肺组织和血清中丙二醛(MDA)和8-异构前列腺素F_(2α)(8-iso-PGF_(2α))含量,并测量血清中超氧化物歧化酶(SOD)活性及肺组织中NADPH氧化酶(NOX4)和SOD1的相对表达量。结果:与N组相比,H_4组的NOX4相对表达量及MDA和8-iso-PGF_(2α)含量均显著升高(P0.05);而与H4组相比,Sal低、高剂量组除m PAP、RV/(LV+S)和WA/TA明显减低外,NOX4的相对表达量及MDA和8-iso-PGF_(2α)含量亦明显减低(P0.05)。与N组相比,H_4组的SOD1相对表达量和SOD活性显著下降,而Sal低、高剂量组的SOD1相对表达量和SOD活性均显著升高并呈剂量依赖性。结论:红景天苷可能通过减轻低氧引起的肺组织氧化应激损伤、恢复氧化/抗氧化系统平衡而起到改善肺动脉高压的作用。     

Protective role of curcumin in nephrotoxic oxidative damage induced by vancomycin in rats

Vancomycin (VAN) is a glycopeptide antibiotic which is active against gram positive bacteria including methicillin resistant Staphylococci. Free radicals are involved in the pathogenesis of vancomycin-induced nephrotoxicity. Therefore, the present study was conducted to investigate the antioxidant potential of curcumin (CUR) against the nephrotoxicity of vancomycin in male rats. Animals used in this study were divided into four groups; the first group was used as control, the second, third and fourth groups were treated orally with curcumin (200 mg/kg BW/day), vancomycin (200 mg/kg BW/day, i.p.), vancomycin plus curcumin, respectively. Curcumin was administered 2 weeks before and 1 week simultaneously with vancomycin. Results showed that thiobarbituric acid reactive substances (TBARS) in plasma and kidney tissue were significantly increased after vancomycin administration. While, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in plasma and kidney tissue and the content of glutathione (GSH) in kidney tissue were decreased compared to control. Vancomycin significantly increased the levels of urea and creatinine. The presence of curcumin with vancomycin caused reduction in induction levels of TBARS in plasma and kidney, urea and creatinine. It ameliorated vancomycin-induced decrease in the activities of antioxidant enzymes and GSH. The presence of curcumin with vancomycin alleviated its nephrotoxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize vancomycin nephrotoxicity.     

Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain

The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.     

Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n = 6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p < 0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.     

Protective effect of octreotide on intra-tracheal bleomycin-induced oxidative damage in rats

The present study is aimed at determining the effect of parenteral octreotide against oxidative damage caused by intra-tracheal bleomycin (BLM) administration. A total of 30 male Wistar rats randomly divided into three groups (control, bleomycin alone, and bleomycin and octreotide) were used in the study. A group of animals received a single dose of intra-tracheal bleomycin (7.5 mg/kg). Animals in another group, which also received intra-tracheal bleomycin, were given 82.5 μg/kg octreotide via i.m. injection for a week. Animals in the control group received neither bleomycin nor octreotide. All animals were sacrificed at the end of the experiment. Serum levels of malondialdehyde, vitamins A, E, and C, selenium levels were determined. In addition, glutathion peroxidase activity levels in erythrocytes were also determined. Malondialdehyde levels and glutathion peroxidase activity were increased whereas antioxidant vitamin levels were decreased significantly in animals that received only bleomycin compared to control animals (p<0.05). The values in rats that received bleomycin and octreotide were found to be closer to the control group (p<0.05). Selenium levels in animals that received only bleomycin were determined to be reduced compared to controls (p<0.05). On the other hand, selenium levels in bleomycin and octreotide groups were similar to control values in (p<0.05). In conclusion, bleomycin induces a severe stress and more importantly increases the amount of free radicals whereas octreotide administration reduces this oxidative damage significantly.     

姜黄素对2 型糖尿病肾病大鼠保护作用及机制研究

目的:探讨姜黄素对2 型糖尿病肾病(DN)大鼠保护作用及可能的作用机制。方法:30 只Wistar 大鼠随机分为对照组、DN 组和姜黄素组,每组10 只。DN 组和姜黄素组采用高脂饲料喂养后注射链脲佐菌素建立DN 模型,造模成功后姜黄素组以200 mg/ kg 姜黄素灌胃,每天1 次,对照组和DN 组给予等量羧甲基纤维素钠灌胃,连续给药12 周。末次给药后收集24 h 尿量,称重,腹腔麻醉后心脏取血,检测血糖(Blood glucose,BG)、总胆固醇(Total cholesterol,TC)、甘油三酯(Triacylglyceride,TG)、血尿素氮(Blood urea nitrogen,BUN)、血肌酐(Serum creatinine,Scr)、尿微量白蛋白(Vrine microalbumin,mAlb),计算尿蛋白排泄率(Urinary protein excretion rate,UAER);处死大鼠,摘取双肾除去包膜后称重(KM),计算肾重指数(KI);多聚甲酚固定肾皮质用于苏木素-伊红(HE)染色,肾皮质制成匀浆检测MDA 和SOD 活性,Western blot 检测肾组织中核因子相关因子2(Nrf2)和血红素加氧酶1(HO鄄1)蛋白表达。结果:DN 组和姜黄素组BG、TC、TG、KI、BUN、Scr、UAER、MDA显著高于对照组,BM、KM、SOD 显著低于对照组,且姜黄素组上述指标升高或降低幅度小于DN 组,差异均有统计学意义(P<0.05);HE 染色结果显示,与DN 组比较,姜黄素组肾小管变性明显减轻,炎性细胞浸润明显减少;Western blot 结果显示对照组Nrf2 和HO-1 蛋白表达显著低于DN 组和姜黄素组,而姜黄素组显著高于DN 组,差异均有统计学意义(P<0.05)。结论:姜黄素可能通过激活Nrf2/ ARE 信号通路,降低糖尿病肾病大鼠氧化应激、发挥肾脏保护作用。     

Progesterone modulates cadmium-induced oxidative stress and inflammation in hepatic tissues of Wistar rats

In recent times, there has been an increased risk of human exposure to cadmium especially in developing countries. We studied the role of progesterone as an anti-inflammatory and antioxidant agent in cadmium induced toxicity. Cadmium toxicity was induced with cadmium chloride (30 mg/kg) per oral while the control group was given distilled water. The Cd group was given CdCl₂ only, P₄ group; progesterone only (10 mg/kg intraperitoneally) and Cd+P₄ group; CdCl₂ and progesterone. All treatments lasted for 21 days. Following sacrifice, liver function tests and antioxidant status were assessed using standard kits; TNFα was immunolocalized across the study groups and the staining intensity measured using Image J software. Cadmium administration induced oxidative stress by a significant elevation in MDA and GC6P levels and a significant reduction in SOD, CAT, and GSH. These were attenuated by progesterone administration. While cadmium exposure caused an increase in serum ALT, AST, and ALP activities, progesterone significantly alleviated these effects. Inflammation shown by significant immunoreactivity in the TNFα positive cells in the liver in the cadmium group was reversed by progesterone. We conclude that cadmium toxicity induces oxidative stress that was attenuated by progesterone.     

Protective effect of leukotriene receptor antagonist montelukast on smoking-induced lung injury in Wistar rats

Increased activation of alveolar macrophage, neutrophil and mast cell has been proven in cigarette smoking (CS)-related lung disorders (CSLD). An increased production of cysteinyl-leukotrienes (LTs), which are mediators secreted from the mentioned cells, in response to CS has been shown in humans. The protective effect of LT1 receptor-1 antagonist (LTR-1AT) on CSLD is, however, not known. In this study we aimed to determine whether there is any protective effect of a LTR-1AT, montelukast (MK), on CSLD in Wistar rats. Nine controls and twenty-three smoke-exposed rats were enrolled into this study. Controls were exposed to non-filtered air, and the smoke-exposed rats were exposed to CS for 6 h/day, 6 days/week for three weeks. The CS-exposed rats were also treated with 0.1 mg/kg/day of MK or saline. Morphometric criteria for lung injury were determined as the mean linear intercept of alveolar septa (Lm), the volume density of alveolar septa (Vvspt) and the density of the alveolar surface area per unit volume of lung parenchyma (Sva.pa). Lung mast cells (LMC), which are a major source of LTs, were also counted. Results showed that Lm of the control group was significantly lower and Vvspt, Sva.pa of the controls were significantly higher compared to those of the CS-exposed groups. Animals treated with MK had significant protection against CSLD. Lm was significantly higher and Vvspt, Sva.pa were lower in the saline group than in the MK-treated group. The number of LMC in the CS-exposed groups was also significantly higher than that in the control group. Based on these results, one can suggest that some part of the pathogenesis of CSLD may be related to an enhanced LTs synthesis and LTR-1AT. Therefore, montelukast may protect against active or passive smoking-induced lung injury and related disorders.     

远志皂苷元对氧化应激损伤的视网膜神经节细胞的保护作用

目的: 观察远志皂苷元(senegenin,Sen)对氧化应激损伤的视网膜神经节细胞(retinal ganglion cells,RGCs)的影响并初步探讨其作用机制。方法: 采用上丘荧光金逆行标记RGCs后,体外原代RGCs混合细胞培养,随机分为control组、H₂O₂组、Sen+H₂O₂和Sen组。检测带荧光金荧光细胞的活力。同上述分组处理视网膜,用Hoechst 33258 染色后观察视网膜细胞核形态的变化,Western blotting检测视网膜细胞cleaved caspase-3、细胞色素C及Bcl-2蛋白的表达。结果: 与control组比较,Sen浓度在10、20和40 μmol/L时, RGCs活力无明显变化(P>0.05),但Sen浓度达到80和160 μmol/L时,RGCs活力明显下降,差异显著(P<0.01)。25、50、100和200 μmol/L H₂O₂明显降低RGCs活力(P<0.05)。Sen浓度在10、20和40 μmol/L时,对50 μmol/L H₂O₂损伤的RGCs有较好的保护作用(P<0.05),其中40 μmol/L Sen保护作用最为明显。Hoechst 33258染色表明Sen可以减少H₂O₂引起的视网膜细胞凋亡。Western blotting结果表明Sen促进Bcl-2蛋白的表达,降低线粒体细胞色素C的释放,下调cleaved caspase-3的表达。 结论: Sen保护RGCs对抗氧化应激引起的损伤,其机制可能与其增强Bcl-2蛋白表达和减少氧化应激引起的细胞凋亡有关。     

Protective effect of sulforaphane against oxidative stress: Recent advances

Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage. Studies on this compound is increasing because its anticarcinogenic and cytoprotective properties in several in vivo experimental paradigms associated with oxidative stress such as focal cerebral ischemia, brain inflammation, intracerebral hemorrhage, ischemia and reperfusion induced acute renal failure, cisplatin induced-nephrotoxicity, streptozotocin-induced diabetes, carbon tetrachloride-induced hepatotoxicity and cardiac ischemia and reperfusion. This protective effect also has been observed in in vitro studies in different cell lines such as human neuroblastoma SH-SY5Y, renal epithelial proximal tubule LLC-PK1 cells and aortic smooth muscle A10 cells. Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms.     

姜黄素预处理及缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用

背景：有研究发现姜黄素预处理、缺血后处理对大鼠肾脏缺血再灌注损伤具有保护作用。 目的：建立大鼠肾脏缺血再灌注损伤模型,观察姜黄素预处理、缺血后处理、姜黄素预处理联合缺血后处理对大鼠肾脏缺血再灌注损伤的保护作用。 方法：60只SD雄性大鼠随机均分为5组,假手术组、肾脏缺血再灌注模型组、姜黄素组、缺血后处理组以及联合处理组。肾脏再灌注24 h后,取下腔静脉血测定肌酐和尿素氮。肾组织测定超氧化物岐化酶活性和丙二醛含量,并行苏木精-伊红染色观察各组肾组织病理学变化。 结果与结论：与假手术组比较,其余各组肌酐、尿素氮均升高(P < 0.05)。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的肌酐、尿素氮值在再灌注24 h后均下降(P < 0.05)。与姜黄素组和缺血后处理组比较,联合处理组的肌酐更低(P < 0.05)。与假手术组比较,缺血再灌注模型组超氧化物歧化酶活性明显降低,丙二醛含量明显升高,差异有显著性意义(P < 0.05)。与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组的超氧化物歧化酶活性升高,丙二醛含量降低,差异有显著性意义(P < 0.05)。与姜黄素组和缺血后处理组比较,联合处理组的超氧化物歧化酶活性升高,差异有显著性意义(P < 0.05)。与假手术组比较,缺血再灌注模型组肾小管损伤明显;与缺血再灌注模型组比较,姜黄素组、缺血后处理组和联合处理组肾小管损伤减轻明显,与姜黄素组和缺血后处理组比较,联合处理组损伤更轻。说明示姜黄素预处理和缺血后处理联合应用具有协同作用,可以更好的保护大鼠缺血再灌注损伤肾脏。     

蜕皮甾酮减轻心肌细胞氧化应激损伤

目的:研究蜕皮甾酮对心肌细胞氧化损伤的作用。方法:H9c2细胞常规培养,经过氧化氢(H_2O_2)处理后建立损伤模型,分为:对照组,蜕皮甾酮高剂量(2μmol/L)、中剂量(1.5μmol/L)和低剂量(1μmol/L)组,H_2O_2组。CCK-8法检测蜕皮甾酮对H9c2细胞活力的影响;流式细胞术检测H9c2细胞的凋亡率;用分光光度法检测乳酸脱氢酶、肌酸激酶同工酶的活性以及丙二醛、超氧化物歧化酶含量;激光共聚焦联合流式细胞术观察细胞内活性氧簇(ROS)的产生和线粒体膜电位的变化;用Western blot法检测H9c2细胞内Bax、Bcl-2和cleaved caspase-3的蛋白水平。结果:在所选浓度范围内,蜕皮甾酮对H9c2细胞的活力无明显影响。与对照组比较,H_2O_2组H9c2细胞的LDH、CK-MB、ROS、MDA及凋亡率明显增加,通过不同浓度的蜕皮甾酮作用后,H9c2细胞的LDH、CK-MB、ROS、MDA及凋亡率显著下降,与H_2O_2组比较差异有统计学显著性。与对照组比较,H_2O_2组H9c2细胞的SOD和线粒体膜电位明显下降;与H_2O_2组比较,蜕皮甾酮高、中、低剂量组H9c2细胞的SOD和线粒体膜电位明显提高。对比对照组,H_2O_2组中H9c2细胞Bax和cleaved caspase-3的蛋白水平明显升高,Bcl-2的表达水平明显下降;与H_2O_2组比较,蜕皮甾酮高、中、低剂量组中H9c2心肌细胞表达Bcl-2蛋白上升,Bax和cleaved caspase-3的蛋白水平下降。结论:蜕皮甾酮对氧化应激条件下的H9c2细胞具有保护功能,其机制可能和减少氧化应激产物,增强抗氧化酶功能,调节线粒体功能和抑制细胞凋亡相关。     

姜黄素类似物L6H4对2型糖尿病大鼠膈肌的保护作用

目的:探讨姜黄素类似物L6H4对2型糖尿病大鼠膈肌的保护作用及机制。方法:40只SPF级雄性SD大鼠,随机均分成5组:正常对照(NC)组、高脂(HF)组、高脂治疗(FT)组、糖尿病(DM)组和糖尿病治疗(DT)组。后4组采用高脂饲料喂养,4周后DM组及DT组腹腔注射链脲佐菌素诱导2型糖尿病模型,造模成功后FT组和DT组用L6H4灌胃治疗8周。生化法检测空腹血糖及血脂水平;放射免疫法检测空腹血清胰岛素(FINS)水平并计算胰岛素抵抗指数(HOMA-IR);ELISA法检测血清脂联素(APN)水平;光镜和电镜观察大鼠膈肌形态改变;酶组织化学染色观察膈肌内脂质沉积及琥珀酸脱氢酶(SDH)和还原型辅酶Ⅰ四氮唑还原酶(NADH-TR)活性;硫代巴比妥酸法和羟胺法分别检测膈肌丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性;免疫组化和Western blot检测膈肌脂联素受体1(AdipoR1)蛋白的表达。结果:HF组和DM组大鼠的血糖、血脂、FINS和HOMA-IR较NC组均有升高(P0.01),L6H4治疗后均下降(P0.01);HF组与DM组大鼠血清APN水平较NC组下降,L6H4治疗后升高(P0.01)。HF组及DM组大鼠膈肌纤维萎缩,肌纤维内脂肪颗粒堆积,线粒体轻微肿胀;DM组大鼠膈肌纤维化,L6H4治疗后,大鼠膈肌的形态学损害减轻。HF组和DM组大鼠膈肌MDA含量及SDH和NADH-TR活性较NC组升高,L6H4治疗后下降(P0.05);HF组和DM组大鼠膈肌SOD活性和AdipoR1蛋白表达较NC组下降,L6H4治疗后升高(P0.05)。结论:姜黄素类似物L6H4对2型糖尿病大鼠的膈肌具有保护作用;膈肌AdipoR1蛋白表达增强、血清APN浓度增加及抗脂质过氧化可能参与其中。     

Co-administration of iron sulphate and nitroglycerin promoted oxidative stress and mild tissue damage in Wistar rats

There is no clear-cut understanding yet of the effect of a sustained production of nitric oxide (NO) either through endogenous or exogenous source on the iron (Fe) metabolism in living cells. Albeit, there are evidences linking decreased NO production to increased iron levels. A high level of free iron in living cells, predispose such systems to oxidative damage through the promotion of free hydroxyl radical generation. On the other hand, a continuous and sustained high level of NO could contribute to cellular damage arising from the debilitating effect of peroxynitrite, a very reactive free radical formed between free NO and superoxide anion. This study investigated the biochemical influence of individual or co-administration of two drugs; nitroglycerin (NGC) and ferrous sulphate (FeSO₄) in rats. Data revealed elevated levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase as well as high malondialdehyde concentrations. Consequently, the levels of superoxide dismutase and catalase were raised. The histopathological presentations show the presence of gradual and subtle cellular damage. We present evidence that individual or co-administration of FeSO₄ or NGC promoted the generation of free radical species which might have caused the tissue damage observed.     

Alcohol-induced oxidative stress in rat liver microsomes: Protective effect of Emblica officinalis

The protective effect of Emblica officinalis fruit extract (EFE) against alcohol-induced oxidative damage in liver microsomes was investigated in rats. EFE (250 mg/kg b.wt/day) and alcohol (5 g/kg b.wt/day, 20%, w/v) were administered orally to animals for 60 days. Alcohol administration significantly increased lipid peroxidation, protein carbonyls with decreased sulfhydryl groups in microsomes, which were significantly restored to normal levels in EFE and alcohol co-administered rats. Alcohol administration also markedly decreased the levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in the liver microsomes, which were prevented with EFE administration. Further, alcohol administration significantly increased the activities of cytochrome P-450, Na⁺/K⁺ and Mg²⁺ ATPases and also membrane fluidity. But, administration of EFE along with alcohol restored the all above enzyme activities and membrane fluidity to normal level. Thus, EFE showed protective effects against alcohol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and restoring the various membrane bound and antioxidant enzyme activities to normal levels, and also by protecting the membrane integrity in rat liver microsomes. In conclusion, the polyphenolic compounds including flavonoid and tannoid compounds present in EFE might be playing a major role against alcohol-induced oxidative stress in rats.     

辛伐他汀对糖尿病大鼠肾脏氧化应激的抑制作用

目的：研究辛伐他汀对糖尿病大鼠肾脏氧化应激反应和肾脏功能的影响。 方法： 链脲佐菌素诱导的糖尿病大鼠，给予辛伐他汀治疗8周后，检测辛伐他汀对糖尿病大鼠肾脏氧化应激水平和肾功能的影响。 结果： 糖尿病组大鼠血清和肾皮质超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性显著低于正常对照组，丙二醛(MDA)含量明显高于正常对照组，同时血尿素氮（BUN）、血肌酐（Scr）、尿白蛋白排泄率（UAER）、尿白蛋白/肌酐、肾重及肾肥大指数（肾重/体重）均高于对照组。辛伐他汀治疗组SOD活性与糖尿病组无明显差异，其余异常均明显轻于糖尿病组。 结论： 辛伐他汀能有效抑制糖尿病大鼠肾脏氧化应激反应，改善肾脏功能。     

红景天苷对非酒精性脂肪性肝炎大鼠肝组织氧化应激的抑制作用

 目的：观察红景天苷（salidroside ,SDS）对大鼠非酒精性脂肪性肝炎（NASH）肝组织氧化应激的影响。方法：以高脂高胆固醇饮食14周诱导建立大鼠NASH模型,药物干预组在造模第8周末时给予SDS 300 mg·kg-1·d-1体重灌胃连续6周,在14周末检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇（TC）和甘油三酯（TG）,以及肝组织TC、TG、丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）含量的变化,ELISA检测8-异前列腺素F2α(8-iso-PGF2α)的水平变化, HE染色观察肝组织病理学变化,免疫组化观察8-羟基脱氧鸟苷酸（8-OHdG）表达的变化。结果：在14 周末, NASH模型组大鼠肝组织病理学检查显示肝组织呈中重度脂肪变性并同时伴有炎症细胞浸润;与正常对照组相比,NASH模型组大鼠血清ALT、AST、TG和TC,以及肝TG、TC和MDA的含量显著上升,而肝SOD和GSH的含量显著下降,8-iso-PGF2α的水平显著上升,免疫组化显示8-OHdG表达的阳性细胞数显著增多。与模型组相比,SDS药物干预组大鼠ALT、AST、TG、TC、MDA和8-iso-PGF2α的含量均显著下降,而肝SOD和GSH的含量显著上升,肝病理学变化得到显著改善,8-OHdG表达的阳性细胞数明显减少。结论：SDS对高脂高胆固醇饮食诱导的NASH有较好的抑制效果,其机制可能与SDS的抗氧化作用有关。     

Protective role of dietary polyphenols in oxidative stress

The oxidative break down of the membrane polyunsaturated fatty acids is known to be accompanied by the formation of a complex mixture of lipidhydroperoxides and secondary products. These compounds are highly reactive and are capable of rapid reaction with cellular nucleophiles such as phospholipids and proteins, and it was found that these reaction products are candidates as impotant biomarkers to evaluate antioxidative activity of dietary antioxidants. The author has been involved in developing immunochemical detection methods for oxidative stress by application of polyclonal and monoclonal antibodies. From the hypothesis that endogenous antioxidants in plants must play an important role for antioxidative defense systems from oxidative stress, an intensive search for novel type of natural antioxidants has been carried out from numerous plant materials, including those used as foods, and we have isolated and identified a number of lipid-soluble and water-soluble dietary antioxidants from crop seeds, sesame seeds and some spices. In this paper, the recent progress of research on functions of dietary antioxidants is reviewed.