D-半乳糖亚急性衰老大鼠模型的建立及评价

目的建立D-半乳糖致大鼠亚急性衰老模型,对该模型进行探讨和评价。方法健康青年SD大鼠共60只,雌雄各半。分别分为2组,半乳糖组大鼠皮下每天注射半乳糖400 mg/kg,对照组每天注射等量生理盐水;老年鼠20只,雌雄各半,不做处理。实验开始后,每周记录体重变化情况,第7周末测试大鼠空间学习能力,第8周末测试大鼠空间记忆能力,计算大鼠胸腺、脾脏、睾丸和卵巢的脏器系数,测定血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量。结果半乳糖注射4 w后,雄性大鼠的体重比对照组显著性降低(P<0.05),注射6 w后,体重差异非常显著性降低(P<0.01);半乳糖组雌雄大鼠的空间学习能力和记忆能力较对照组显著性降低(P<0.05),听力阈值显著增加(P<0.05),胸腺指数非常显著性降低(P<0.01),雄性大鼠睾丸系数显著性降低(P<0.05),血清SOD活性显著性降低(P<0.05),MDA含量显著性增高(P<0.05);其余实验结果组间比较差异没有显著性(P>0.05)。结论 D-半乳糖皮下注射8 w可以复制出与24月龄老年大鼠自然衰老程度相似的亚急性衰老模型,雄性大鼠优于雌性大鼠。     

D-半乳糖合并半高脂饲料致认知功能障碍大鼠模型的建立及评价

目的 建立复合因素所致认知功能障碍大鼠模型,并从行为学、病理形态学、细胞凋亡、氧化损伤和炎症因子等角度进行评价.方法 选用雌性正常SD大鼠,采用皮下注射D-半乳糖及饲喂半高脂饲料,制备6 w及8 w不同时程的认知功能障碍动物模型.采用Morris水迷宫实验及物体识别实验检测各组大鼠学习记忆能力;采用HE染色及电镜观察海马组织病理形态;测定脑中丙二醛(MDA)、氧化低密度脂蛋白(ox-LDL)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)的含量;比较不同时程认知功能障碍模型大鼠之间及与正常大鼠的差异.结果 6 w末时,认知功能障碍模型大鼠在物体识别实验中,分辨指数较空白组明显下降(P＜0.05),但水迷宫实验成绩与空白组比较无明显差异;而8 w末时,模型动物在分辨指数下降(P＜0.01)的同时,水迷宫成绩亦明显下降,逃避潜伏期明显延长(P＜0.01),穿台次数明显减少(P＜0.05);8 w末与6 w末相比,水迷宫实验逃避潜伏期明显延长(P＜0.01);造模后,能引起海马神经细胞的退行性改变及早期凋亡现象,且存在着进行性加重的病理变化;6、8 w模型组大鼠脑组织的TNF-α、IL-6水平显著升高(P＜0.05,P＜0.01),同时8 w大鼠IL-6水平高于6 w模型组(P＜0.05);6、8 w模型组ox-LDL、MDA水平均显著升高(P＜0.05,P＜0.01).结论 以该方法复制的认知功能障碍大鼠模型,在一定程度上模拟了认知功能障碍发生、发展的多环节病理变化,可为认知功能障碍的治疗,特别是其早期干预打下基础.     

何首乌饮对D-半乳糖所致衰老大鼠下颌下腺β-半乳糖苷酶表达的影响

目的 通过观察何首乌饮干预的衰老大鼠下颌下腺β-半乳糖苷酶(β-gal)表达的改变,探讨何首乌饮的抗衰老作用.方法 用D-半乳糖制造衰老大鼠模型,何首乌饮的干预作用分治疗和预防两部分,检测β-半乳糖苷酶活性,观察下颌下腺衰老细胞数目改变.结果 预防性实验部分:模型组衰老细胞数目多于正常组和各预防性用药组;治疗性实验部分:用药各组与自然恢复组相比,衰老细胞数目明显减少,其中治疗中剂量组最低.结论 何首乌饮具有抗模型大鼠下颌下腺细胞衰老的作用.     

腹腔和皮下注射D-半乳糖衰老大鼠模型分析

目的 探讨腹腔和皮下注射D-半乳糖建立衰老大鼠模型间的差异.方法 分别腹腔和皮下连续注射D-半乳糖40d后,称量大鼠体重,取血测血糖、C反应蛋白(CRP)、丙二醛(MDA)含量;总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性.取胸腺、脾脏、皮肤和脑组织,称量胸腺和脾脏重量,测脑组织单胺氧化酶(MAO-B)活性和皮肤羟脯氨酸含量,同时制作切片.结果 经过比较发现,皮下注射组CRP含量较腹腔注射组高(P＜0.05);T-SOD活性和GSH-Px活性较腹腔注射组高(P ＜0.01);MDA含量较腹腔注射组低(P＜0.01);皮肤羟脯氨酸含量较腹腔注射组低(P＜0.05),但脑组织MAO-B活性、胸腺指数、脾脏指数和血糖并无明显差异.结论两种方法均能建立稳定可靠的衰老大鼠模型.两种模型均能在多层面上反映出机体的衰老情况,腹腔注射法在构建大鼠衰老模型上效果更明显.     

D-半乳糖加速衰老合并Meynert核损毁大鼠学习记忆能力变化的初步观察

1997年3～7月,在大鼠D-半乳糖加速衰老模型基础上,注射鹅膏蕈氨酸(ibotenic acid,IBO)损毁脑Meynert核制造了新的痴呆大鼠模型,并对其学习记忆能力的改变进行了初步观察和评价。     

鸡冠花对D-半乳糖致小鼠衰老作用的研究

目的　研究鸡冠花的抗衰老作用。方法　随机将小鼠分为 A(正常对照组 )、B(衰老对照组 )、C(鸡冠花高剂量组 ) D(鸡冠花低剂量组 )四组。每组 1 4只 ,雌雄各半 ,除 A组外 ,其余三组每天注射 0 .1 g/ kg D-半乳糖 ,建立衰老动物模型 ,C、D两组同时施加不同剂量鸡冠花 ,连续 8w,测定各组血清超氧化物歧化酶 ( SOD)、谷胱甘肽过氧化物酶 ( GSH- Px)活性 ,总抗氧化能力 ( T- AOC) ,丙二醛 ( MDA)和肝脏脂褐质 ( L F )含量。结果　衰老对照组 SOD、GSH- Px活性和 T- AOC较正常对照组明显降低 ( P<0 .0 5) ,MDA和 L F含量增加 ( P<0 .0 5) ,呈现衰老状态。鸡冠花两组 SOD、GSH- Px活性和 T- AOC较衰老对照组明显升高 ( P<0 .0 5) ,MDA和 L F含量减少 ( P<0 .0 5)。结论　鸡冠花具有拮抗 D-半乳糖致衰老作用     

D-半乳糖致衰大鼠非酶糖基化改变及菟丝子醇提液对其作用的研究

目的 研究D-半乳糖致衰大鼠非酶糖基化作用及菟丝子醇提液对其影响,探讨衰老发生的机制及菟丝子延缓衰老作用的机制.方法 采用D-半乳糖制作衰老大鼠模型,观察15、30、45 d时的糖化血红蛋白(GHb)、丙二醛(MDA)、超氧化物岐化酶(SOD)活性的变化.采用半定量RT-PCR法测定大鼠胸主动脉糖化终末产物受体(RAGE)mRNA的表达,并观察菟丝子醇提液对其影响.结果 D-半乳糖导致GHb、MDA和RAGE-mRNA水平升高(P＜0.01),SOD活性降低(P＜0.01),并呈现时间渐进性改变.菟丝子醇提液使大鼠GHb、MDA降低(P＜0.01),SOD活性增加(P＜0.01),RAGE-mRNA表达水平降低(P＜0.01).结论 D-半乳糖诱导非酶糖基化发生,菟丝子醇提液抑制D-半乳糖致衰大鼠非酶糖基化反应,在给药30d即有显著的作用效果.     

何首乌饮对D-半乳糖所致衰老大鼠下颌下腺超微结构的影响

目的 观察实验性衰老大鼠下颌下腺超微结构的改变,探讨何首乌饮的干预作用.方法 用D.半乳糖制造衰老大鼠模型,用何首乌饮干预(预防和治疗),观察下颌下腺主要细胞器超微结构改变.结果 模型组大鼠下颌下腺细胞器的超微结构呈现明显的退行性变;何首乌饮预防组下颌下腺细胞器的超微结构退行性变的情况明显好于治疗组,治疗组改变程度较自然恢复组明显减轻.结论 D-半乳糖模型大鼠下颌下腺超微结构发生明显衰老改变,何首乌饮可改善衰老大鼠下颌下腺超微结构的衰老变化,预防用药效果更好.     

珍珠梅水提取物对D-半乳糖中毒大鼠急性肝损伤的防护作用

目的：研究珍珠梅水提取物对D-半乳糖所致大鼠急性肝损伤的防护作用。方法：50只大鼠随机分为正常组、模型组、大和小剂量给药组、阳性对照纽5个组。给药组按10g／k、5g／k剂量以珍珠梅水提取物灌胃；阳性对照组按0．2g／k剂量以联苯双酯灌胃；正常组、模型组以等体积生理盐水灌胃；共5天。第4天，模型组和给药组按0．5g／kg剂量腹腔注射D-半乳糖，正常组腹腔注射等体积生理盐水。腹腔注射D-半乳糖24小时后，摘眼球取血，用比色分析法测定大鼠血清AST、ALT的活性，血清和线粒体超氧化物歧化酶(superoxide dismutase，SOD)、谷胱甘肽过氧化物酶(glutathione perioxidase，GSH-PX)的活性及丙二醛(malondialdehyde，MDA)的含量。结果：珍珠梅水提物显著降低因D-半乳糖所引起的大鼠血清ALT、AST的升高；对血清SOD、GSH-PX活性有明显的升高作用；对MDA含量有降低作用。结论：珍珠梅水提物对D-半乳糖所致大鼠急性肝损伤有防护作用。     

氧化应激对D-半乳糖致衰老小鼠的影响

目的 探讨氧化应激与衰老的相互关系.方法 应用腹腔注射D-半乳糖方法建立衰老模型,观察实验小鼠的外观特征,测定其运动能力、免疫器官指数(胸腺指数、脾脏指数)、脾淋巴细胞增殖活性、血清和脑组织中的SOD及MDA含量,并进行统计学分析.结果 与对照组相比,D-半乳糖腹腔注射后小鼠运动能力、脾指数、胸腺指数及脾细胞增殖活性下降(均P＜0.01),SOD的活性降低(P＜0.01),MDA的含量升高(P＜0.01).结论 氧化应激参与了衰老的发生发展过程,降低了机体的免疫功能和抗氧化能力.     

Lipid peroxidation and antioxidant status in colorectal cancer

AIM: Reactive oxygen species (ROS) can induce carcinogenesis via DNA injury. Both enzymatic and non-enzymatic parameters participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the levels of final lipid peroxidation products like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in primary colorectal cancer. Moreover, we analysed the activity of main antioxidative enzymes, superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSRG-R) and the level of non-enzymatic antioxidants (glutathione, vitamins C and E). METHODS: Investigations were conducted in 81 primary colorectal cancers. As a control, the same amount of sample was collected from macroscopically unchanged colon regions of the most distant location to the cancer. Homogenisation of specimens provided 10% homogenates for our evaluations. Activity of antioxidant enzymes and level of glutathione were determined by spectrophotometry. HPLC revealed levels of vitamins C and E and served as a method to detect terminal products of lipid peroxidation in colorectal cancer. RESULTS: Our studies demonstrated a statistically significant increase in the level of lipid peroxidation products (MDA-Adc. muc.-2.65±0.48 nmol/g, Adc.G3-2.15±0.44 nmol/g, clinical IV stage 4.04±0.47 nmol/g, P<0.001 and 4-HNE-Adc.muc. -0.44±0.07 nmol/g, Adc.G3-0.44±0.10 nmol/g, clinical IV stage 0.52±0.11 nmol/g, P<0.001) as well as increase of Cu,Zn-SOD (Adc.muc.-363±72 U/g, Adc.G3-318?8 U/g, clinical IV stage 421±58 U/g, P<0.001), GSH-Px (Adc.muc. -2143±623 U/g, Adc.G3-2005±591 U/g, clinical IV stage 2467±368 U/g, P<0.001) and GSSG-R (Adc.muc.-880±194 U/g, Adc.G3-795±228 U/g, dinical IV stage 951±243 U/g, P<0.001) in primary tumour comparison with normal colon (MDA-1.39±0.15 nmol/g, HNE-0.29±0.03 nmol/g, Cu, Zn-SOD-117±25 U/g, GSH-Px-1723±189 U/g, GSSG-R-625±112 U/g) especially in mucinous and G3-grade adenocarcinomas as well as clinical IV stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40±14 U/g, clinical IV stage 33±18 U/g vs 84±17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical IV stage 150±48 nmol/g vs 167±15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical IV stage 325±92 nmol/g vs 513?4 nmol/g, P<0.001; vit. E-clinical IV stage 13.3±10.3 nmol/g vs 37.5±5.2 nmol/g). CONCLUSION: Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer.     

联合检测氨基末端脑钠肽前体和肌钙蛋白对肺炎并心力衰竭的诊断价值

目的评估氨基末端脑钠肽前体（NT—proBNP）心肌肌钙蛋白T（cTnT）对肺炎并心力衰竭（肺炎心衰）的诊断价值。方法选择肺炎心衰患儿52例,健康儿童23名,检测血清NT—proBNP、cTnT及肌酸激酶同工酶（CK—MB）。结果肺炎心衰组患儿血清NT—proBNP、cTnT及CK—MB显著高于健康对照组。肺炎心衰组NT—proBNP的敏感性优于cTnT。结论联合检测NT—proBNP、cTnT对肺炎患者合并心肌损伤、心功能不全的诊断有重要意义。     

Lipid peroxidation in lung of rat stressed by immobilization: Effects of vitamin E supplementation

This study was carried out to examine the possibility of initiation of lipid peroxidation in the lung of Wistar albino male rats stressed by immobilization. The effects of vitamin E supplementation were also investigated. We found that immobilization of rats with normal pulmonary content of vitamin E caused lipid peroxidation in the lung. Decrease of the lung content of unsaturated fatty acids and vitamin E was also established. The immobilization-induced changes of all of these parameters were significantly inhibited by vitamin E injection (100 mg/kg body weight) for 7 days. A possible sequence of events leading to the initiation of lipid peroxidation and lung cell membrane damage in rats stressed by immobilization is discussed. Offprint requests to: Stefan Ribarov, PhD     

Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats with streptozotocin-induced diabetes

Reactive oxygen species have been related to the pathogenesis of various diseases, including diabetes mellitus. Nicotinamide has been used for the prevention of the diabetogenic effects of streptozotocin (STZ) in animals. In the present study we assessed the effect of diets with deficient, normal or 17-fold supplemented nicotinamide concentrations on the rate of lipopoeroxidation in animals with STZ-induced diabetes. Male Wistar rats were divided into three groups kept on one of the diets for six weeks: DD, diabetic rats on a nicotinamide-deficient diet; DN, diabetic rats on a normal nicotinamide diet; and DS, diabetic rats on a nicotinamide-supplemented diet. During the fourth week of the experiment all animals were fasted for 24 hours and injected into the tail vein with a single STZ dose (40 mg/kg weight). Eight animals from each of the six groups were then sacrificed 24 hours, 1 week and 2 weeks after STZ injection. Mean pancreatic thiobarbituric acid reactive substances (TBARS) (nmol/mg tissue) were significantly lower in the DS group (p < 0.05) compared to the DN and DD groups at 24 hours and during the first week. Hepatic TBARS concentrations (nmol/mg protein) did not differ between groups. Mean hepatic reduced glutathione (GSH) levels were significantly higher (46.76 ± 12.33 nmol/mg protein) in the DS group compared to the DD (32.90 ± 6.70) and DN (24.55 ± 6.41) groups, but only after the 24-hour period. Hepatic vitamin E consumption (Μg/g tissue) was considerable in the groups not supplemented with nicotinamide, whereas vitamin E levels were unchanged in the supplemented group. In contrast, plasma vitamin E levels were decreased in the normal and supplemented groups after 1 and 2 weeks. A higher N-methylnicotinamide excretion (μg/ 24 hours) occurred in the supplemented group. We conclude that, after induction of diabetes with STZ, nicotinamide supplementation protected from the damage caused by the toxic action of STZ, promoting lower lipid peroxidation. Received: 27 September 1999 / Accepted in revised form: 3 March 2000     

Studies on cumene hydroperoxide-induced lipid peroxidation in the isolated perfused rat heart

In the isolated, perfused rat heart, lipid peroxidation, induced by cumene hydroperoxide (Cum OOH), is accompanied by the release of malondialdehyde (MDA). Using a modified perfusion technique resulting in the separate collection of coronary and interstitial effluent, it can be shown that upon Cum OOH (0.5 mM) perfusion there is an immediate release of MDA in the coronary effluent and a delayed release in the interstitial fluid, indicating the susceptibility and coronary vascular tissue towards free radical-induced lipid peroxidation. Perfusion with Cum OOH leads to an initial increase of the coronary flow and a depressed contractility followed by a cardiac arrest concomitantly with the onset of MDA release in the interstitial fluid. Finally, during prolonged perfusion the coronary flow diminishes and contracture of the heart muscle ('stone heart') develops. These phenomena resemble those occurring during the 'calcium paradox'. Although the contractility diminishes immediately after the perfusion with Cum OOH the tissue ATP level and energy charge (formula; see text) remain constant. From the moment of cardiac arrest the ATP and creatine phosphate levels gradually decrease and the energy charge drops simultaneously with the appearance of MDA in the interstitial fluid. In contrast to the calcium paradox there is no simultaneous increase in the myocardial AMP level. Various mitochondrial enzymes (cytochrome c oxidase, monoamine oxidase, carnitinepalmitoyltransferase I and palmitoyl CoA synthetase) were tested and not affected by Cum OOH perfusion. During the development of contracture after 20 min of Cum OOH perfusion massive contraction band necrosis of cardiac tissue occurs. However, overall protein release is lower when compared with the protein release during the calcium paradox.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early Alcoholic Liver Injury: Formation of Protein Adducts with Acetaldehyde and Lipid Peroxidation Products, and Expression of CYP2E1 AND CYP3A

The formation of protein adducts with reactive aldehydes resulting from ethanol metabolism and lipid peroxidation has been suggested to play a role in the pathogenesis of alcoholic liver injury. To gain further insight on the contribution of such aldehydes in alcoholic liver disease, we have compared the appearance of acetaldehyde, malondialdehyde, and 4-hydroxynonenal adducts with the expression of cytochrome P-450IIE1, and cytochrome P-4503A enzymes in the liver of rats fed alcohol with a high-fat diet for 2 to 4 weeks according to the Tsukamoto-French procedure and in control rats (high-fat liquid diet or no treatment). Urine alcohol and serum aminotransferase levels were recorded, and the liver pathology was scored from 0 to 10 according to the presence of steatosis, inflammation, necrosis, and fibrosis. The ethanol treatment resulted in the accumulation of fat, mild necrosis and inflammation, and a mean liver pathology score of 3 (range: 1 to 5). Liver specimens from the ethanol-fed animals with early alcohol-induced liver injury were found to contain perivenular, hepatocellular acetaldehyde adducts. Malondialdehyde and 4-hydroxynonenal adducts were also present showing a more diffuse staining pattern with occasional sinusoidal reactions. In the control animals, a faint positive reaction for the hydroxynonenal adduct occurred in some of the animals fed the high fat diet, whereas no specific staining was observed in the livers from the animals receiving no treatment Expression of both CYP2E1 and CYP3A correlated with the amount of protein adducts in the liver of alcohol-treated rats. Distinct CVP2E1 -positive immunohistochemistry was seen in 3 of 7 of the ethanol-fed animals. In 5 of 7 of the ethanol-fed animals, the staining intensities for CYP3A markedly exceeded those obtained from the controls. The present findings indicate that acetaldehyde and lipid peroxidatjon-derived adducts are generated in the early phase of alcohol-induced liver disease. The formation of protein adducts appears to be accompanied by induction of both CVP2E1 and CVP3A.     

Generation of aldehyde-derived protein modifications in ethanol-exposed heart

BACKGROUND: Although excessive ethanol consumption is known to lead to a variety of adverse effects in the heart, the molecular mechanisms of such effects have remained poorly defined. We hypothesized that posttranslational covalent binding of reactive molecular species to proteins occurs in the heart in response to acute ethanol exposure. METHODS: The generation of protein adducts with several aldehydic species was examined by using monospecific antibodies against adducts with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl radicals. Specimens of heart tissue were obtained from rats after intraperitoneal injections with alcohol (75 mmol/kg body weight) with or without pretreatment with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor. RESULTS: The amounts of MDA and unreduced AA adducts were found to be significantly increased in the heart of the rats treated with ethanol, cyanamide, or both, whereas no other adducts were detected in statistically significant quantities. Immunohistochemical studies for characterization of adduct distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated with ethanol and cyanamide in addition to intracellular adducts, which were also present in the group treated with ethanol alone. CONCLUSIONS: These findings support the role of enhanced lipid peroxidation and the generation of protein-aldehyde condensates in vivo as a result of excessive ethanol intake. These findings may have implications in the molecular mechanisms of cardiac dysfunction in alcoholics.     

家兔肝缺血再灌注损伤中脂质过氧化反应及人参多糖的干预

目的 观察肝缺血再灌注损伤时脂质过氧化的变化以及人参多糖的干预作用,并探究其机制.方法 30只家兔随机均分为对照组、缺血再灌注组和人参多糖组.观察血浆及肝组织中丙二醛含量及超氧化物歧化酶、谷胱甘肽过氧化物酶、黄嘌呤氧化酶和丙氨酸氨基转移酶活力变化,光镜下观察肝组织结构变化,并观察人参多糖对上述指标的影响.结果 缺血再灌注组血浆超氧化物歧化酶和谷胱甘肽过氧化物酶活力在肝脏缺血45 min以及再灌注45 min逐步降低,丙氨酸氨基转移酶、黄嘌呤氧化酶活力和丙二醛含量明显升高.人参多糖组血浆超氧化物歧化酶和谷胱甘肽过氧化物酶活力与缺血前比无明显下降,丙氨酸氨基转移酶、黄嘌呤氧化酶活力和丙二醛含量无明显升高,尤其再灌注45 min血浆超氧化物歧化酶活力显著高于缺血再灌注组同期(P<0.01),丙氨酸氨基转移酶、黄嘌呤氧化酶活力和丙二醛含量显著低于缺血再灌注组同期水平(P<0.01).肝组织超氧化物歧化酶、谷胱甘肽过氧化物酶活力缺血再灌注组明显低于对照组,人参多糖组则明显高于缺血再灌注组(P<0.01);黄嘌呤氧化酶活力和丙二醛含量缺血再灌注组明显高于对照组(P<0.05或P<0.01),而人参多糖组则明显低于缺血再灌注组(P<0.05或P<0.01).光镜下发现缺血再灌注组肝组织细胞形态学结构明显异常,人参多糖组肝组织损伤明显减轻.结论 人参多糖能降低黄嘌呤氧化酶活性,减少氧自由基的生成,并且能增强超氧化物歧化酶、谷胱甘肽过氧化物酶等抗氧化酶的活性,清除氧自由基,抑制脂质过氧化反应,从而有效减轻肝缺血再灌注损伤.     

成年去胸腺大鼠及老年大鼠肝、脑组织脂质过氧化作用的研究

为了研究响腺对自由基反应的彭响,本实验观察了成年去胸腺大鼠和老年大鼠肝、脑过氧化脂质(LPO)的水平。实验结果表明,在去胸腺大鼠中,雌鼠肝脏LPO增高,脑组织LPO无明显变化,而雄鼠肝、脑组织LPO均未见增高;老年大鼠不论雌雄其肝、脑组织的LP0均增高。     

Cardiac overexpression of alcohol dehydrogenase exacerbates cardiac contractile dysfunction,lipid peroxidation,and protein damage after chronic ethanol ingestion

BACKGROUND: Alcoholic cardiomyopathy is manifested as ventricular dysfunction, although its specific toxic mechanism remains obscure. This study was designed to examine the impact of enhanced acetaldehyde exposure on cardiac function via cardiac-specific overexpression of alcohol dehydrogenase (ADH) after alcohol intake. METHODS: ADH transgenic and wild-type FVB mice were placed on a 4% alcohol or control diet for 8 weeks. Mechanical and intracellular Ca2+ properties were evaluated in cardiac myocytes. Levels of acetaldehyde, lipid peroxidation, and protein carbonyl formation were determined. RESULTS: FVB and ADH mice consuming ethanol exhibited elevated blood ethanol/acetaldehyde, cardiac acetaldehyde, and cardiac hypertrophy compared with non-ethanol-consuming mice. However, the levels of cardiac acetaldehyde and hypertrophy were significantly greater in ADH ethanol-fed mice than FVB ethanol-fed mice. ADH transgene itself did not affect mechanical and intracellular Ca2+ properties with the exception of reduced resting intracellular Ca2+ and Ca2+ re-sequestration at low pace frequency. Myocytes from ethanol-fed mice showed significantly depressed peak shortening, velocity of shortening/relengthening, rise of intracellular Ca2+ transients, and sarco(endo)plasmic reticulum Ca2+ load associated with similar duration of shortening/relengthening compared with myocytes from control mice. Strikingly, the ethanol-induced mechanical and intracellular Ca2+ defects were exacerbated in ADH myocytes compared with the FVB group except velocity of shortening/relengthening. The lipid peroxidation end products malondialdehyde and protein carbonyl formation were significantly elevated in both livers and hearts after chronic ethanol consumption, with the cardiac lipid and protein damage being exaggerated by ADH transgene. CONCLUSION: These data suggest that increased cardiac acetaldehyde exposure due to ADH transgene may play an important role in cardiac contractile dysfunctions associated with lipid and protein damage after alcohol intake.