硫代乙酰胺建立大鼠急性肝损伤模型探讨

目的探讨用硫代乙酰胺（Thioacetamide,TAA）制作大鼠急性肝损伤模型时选择TAA的合适剂量、指标检测的最佳时间点以及大鼠的适宜性别。方法一次性腹腔注射不同剂量的TAA制作大鼠急性肝损伤模型,检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）值及肝脏病理学变化。结果TAA200mg／kg的剂量组血清ALT、AST值显著升高,病理学显示肝细胞变性坏死,而且肝脏病理变化均一。各组雌性鼠的各项指标均不如雄性鼠明显。结论在本实验条件下TAA200mg／kg的剂量最佳,雄性鼠优于雌性鼠．给药后24小时急性肝损伤最明显。     

微囊藻毒素LR对小鼠肝脏和淋巴细胞的损伤效应

[目的]研究不同剂量微囊藻毒素LR（MCLR）经灌胃途径对小鼠肝细胞及外周血淋巴细胞细胞的损伤效应。[方法]生化法测定血清中谷丙转氨酶（ALT），谷草转氨酶（AST），碱性磷酸酶（AKP），γ-谷氨酸转移酶（γ-GT）和乳酸脱氢酶（LDH）含量，单细胞凝胶电泳试验（彗星试验）测定外周血淋巴细胞DNA迁移长度。[结果]MCLR在1μg/L浓度下即可引起ALT，LDH的显著升高；在达到100μg/L浓度时可引起ＡＫＰ明显升高；但各剂量组ＡＳＴ，γ－ＧＴ与对照组相比无显著差异；不同剂量ＭＣＬＲ均可引起外周血淋巴细胞ＤＮＡ迁移长度增加，且有剂量－反应关系。［结论］ＭＣＬＲ在１μｇ／Ｌ低浓度下对小鼠肝细胞及外周血淋巴细胞可产生一定损伤作用。     

丙烯酰胺毒性与氧化损伤的实验研究

目的探讨丙烯酰胺毒性与氧化损伤的定量敏感指标。方法将SD大鼠随机分组,雌雄各半。腹腔注射染毒。根据动物实验的LD50（1.5-2.0 mg/kg）,分别按体重设0.5、1.0、1.5μg/kg 3个丙烯酰胺毒素染毒组和空白对照组及溶剂对照组。测定血液生化酶、脏器系数和氧化损伤指标。结果与空白对照组及与溶剂对照组比较,中高剂量组丙氨酸转氨酶（ALT）、超氧化物歧化酶（SOD）活性与丙二醛（MDA）含量明显增加（P〈0.05）,高剂量组动物肝脏脏器系数明显增大（P〈0.05）,心肌损伤特异性标志物天冬氨酸转氨酶（AST）活性水平变化明显（P〈0.05）。肝、肾中ROS含量未见明显差别（P均〉0.05）。结论血清ALT、AST、SOD活性、MDA含量,可作为评价丙烯酰胺毒性与氧化损伤的定量敏感指标。     

硫代乙酰胺建立大鼠急性肝损伤模型探讨

目的探讨用硫代乙酰胺(Thioacetamide,TAA)制作大鼠急性肝损伤模型时选择TAA的合适剂量、指标检测的最佳时间点以及大鼠的适宜性别。方法一次性腹腔注射不同剂量的TAA制作大鼠急性肝损伤模型,检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)值及肝脏病理学变化。结果TAA200mg/kg的剂量组血清ALT、AST值显著升高,病理学显示肝细胞变性坏死,而且肝脏病理变化均一。各组雌性鼠的各项指标均不如雄性鼠明显。结论在本实验条件下TAA200mg/kg的剂量最佳,雄性鼠优于雌性鼠,给药后24小时急性肝损伤最明显。     

火龙果对高血脂模型大鼠的降脂作用实验研究

目的研究“紫红龙”火龙果对高血脂SD大鼠的降脂作用。方法根据TG水平将50只雄性SD大鼠随机分为5组,每组10只,设为阴性对照组、高脂模型对照组、火龙果：7．5、10．0、15．0g／kgbw3个剂量组。剂量组灌胃不同浓度的火龙果果浆,两个对照组灌胃同体积的蒸馏水。3个剂量组、高脂模型对照组动物自由进食高脂饲料,阴性对照组自由进食基础饲料。实验进行45d后处死大鼠取血清测定各组大鼠的甘油三酯（TG）、总胆固醇（CHO）、高密度脂蛋白（HDH—C）、低密度脂蛋白（LDH—C）、谷丙转氨酶（ALT）、谷草转氨酶（AST）,取肝脏称重,计算肝／体重比值,并做病理切片。结果火龙果中剂量组、高剂量组大鼠的TG、CHO、LDH—C较高脂模型组明显降低,差异有统计学意义（P〈0．05）;谷草转氨酶（AST）、肝实质重量、肝／体比值结果表明：高脂饮食除能引起大鼠的血脂升高,还能损害机体的肝脏实质,引起AST升高、肝脏增大;但随火龙果的剂量增加,肝脏受损害的程度逐渐减轻,特别是AST指标,火龙果的高剂量组已恢复至阴性组水平。结论“紫红龙”火龙果对高血脂sD大鼠具有明显的降脂作用。     

鹅膏蕈毒性与氧化损伤的实验研究

目的探讨鹅膏蕈毒性与氧化损伤的定量敏感指标。方法将50只SD大鼠随机分5组,雌雄各半。腹腔注射染毒。根据动物实验的LD50(1.5~2.0 mg/kg),分别按体重设0.5、1.0、1.5μg/kg 3个鹅膏蕈毒素染毒组和空白对照组及溶剂对照组。测定血液生化酶、脏器系数和氧化损伤指标。结果与空白对照组及与溶剂对照组比较,中高剂量组丙氨酸转氨酶(ALT)、超氧化物歧化酶(SOD)活力与丙二醛(MDA)含量明显增加(P<0.05),高剂量组动物肝脏脏器系数明显增大(P<0.05),心肌损伤特异性标志物天冬氨酸转氨酶(AST)活力水平变化明显(P<0.05)。肝、肾中活力氧族含量未见明显差异(P均>0.05)。结论血清ALT、AST、SOD活力、MDA含量,可作为评价鹅膏蕈毒素毒性与氧化损伤的定量敏感指标。     

血清转氨酶长期升高的原因和处理

１转氨酶简介转氨酶是一种血清酶,共有二十余种,用于诊断肝脏疾病的有两种：谷丙转氨酶（ＡＬＴ）和谷草转氨酶（ＡＳＴ）。许多脏器和组织均含有这二种酶,二者的分布大致为：谷丙转氨酶：肝＞肾＞心＞肌肉;谷草转氨酶：心＞肝＞肌肉＞肾。在肝内,谷丙转氨酶存在于肝...     

乌司他丁预处理对大鼠肝缺血再灌注多脏器氧化损伤的保护作用

目的 探讨乌司他丁预处理对大鼠肝缺血再灌注多脏器氧化损伤的保护作用机制。方法 将30只Wistar大鼠随机分为假手术(Sham-Operated,SO)组、缺血-再灌注(Ischemia-Reperfusion,I/R)组、乌司他丁(Ulinastatin,UTI)组,每组各10只。采用Pringle法制备大鼠肝I/R损伤模型。肝缺血30 min、再灌注2 h（SO组除外）,UTI组缺血前预处理UTI（3万 U/kg）。采用比色法检测血清和肝、肾、心肌组织中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cr)、尿素氮(BUN)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)、乳酸脱氢酶(LDH)水平,观察尿量和肝、肾、心肌组织病理学改变。结果 I/R组血清ALT、AST、Cr、BUN、MDA及肝、肾、心肌组织MDA含量均高于SO组(P＜0.05),血清和肝、肾、心肌组织SOD、GSH-Px、GSH、LDH含量均低于SO组(P＜0.05);UTI组血清ALT、AST、Cr、BUN、MDA及肝、肾、心肌组织MDA水平均低于I/R组(P＜0.05),血清和肝、肾、心肌组织SOD、GSH-Px、GSH、LDH含量均高于I/R组(P＜0.05)。I/R组尿量少于SO组(P＜0.05),UTI组尿量多于I/R组(P＜0.05)。组织病理学观察,I/R组肝肾组织有明显的组织损伤,心肌未见明显的组织损伤。UTI组肝肾组织结构变化明显减轻。结论 乌司他丁预处理对大鼠肝I/R后多脏器损伤具有保护作用,其机制可能与提高机体抗氧化能力有关。     

奶蓟益肝片对四氯化碳肝损伤保护作用效果观察

目的探讨奶蓟益肝片对四氯化碳（CCl4）肝损伤的保护作用。方法将46只动物随机分成阴性对照组、CCl4对照组及0.13、0.25g/kg两个剂量组,剂量组每天灌胃给予奶蓟益肝片。30d后,CCl4对照组及剂量组以0.01ml/g的剂量一次性经腹腔注射给予0.125?l4。24h后处死动物,测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）水平,肝脏进行病理组织学检查。结果0.25g/kg剂量组的ALT、AST水平降低,与CCl4对照组比较,差异有显著性（P〈0.05）。0.25g/kg剂量组发生肝细胞坏死的动物例数减少,病变程度减轻,肝细胞坏死评分降低,与CCl4对照组比较,差异亦有显著性（P〈0.05）。结论奶蓟益肝片对CCl4化学性肝损伤具有保护作用。     

杀虫磺原药大鼠亚慢性毒性研究

目的研究杀虫磺原药对大鼠亚慢性经口毒性,探讨其亚慢性毒性的阈作用剂量和最大无作用剂量。方法雌鼠剂量以135、67.50、22.50mg/kg,雄鼠剂量以157.5、78.752、6.25mg/kg,连续90d给予杀虫磺原药,观察动物的一般状况,体重增长及血液、生化指标并解剖进行病理检查。结果杀虫磺原药高剂量组动物,染毒8周后出现被毛蓬松、活动减少、体重减轻等症状;染毒结束后血清中谷草转氨酶（AST）升高,肝及雄鼠肾脏器系数增大,组织病理学检查显示：肝细胞明显浊肿,胞浆疏松,汇管区可见慢性炎细胞浸润。中剂量组动物染毒结束后谷草转氨酶（AST）显著升高,雄鼠肾脏器系数增大;肝细胞病变相同,但程度较轻。低剂量组动物一般行为、体重增长、尿常规、血液学、血液生化学、脏器重量、脏器系数及病理学检查均未见变化。结论本实验条件下,初步确定大鼠90d亚慢性经口最大无作用剂量,雌性为22.50mg/kg;雄性为26.25mg/kg。     

二甲基甲酰胺与乙醇联合毒性初探

经口分别给予Wistar大鼠蒸馏水、DMF 400mg/kg、乙醇1000mg/kg及DMF400mg/kg 乙醇1000mg/kg,染毒21天。结果表明DMF组及联合染毒组大鼠血清ALT明显增高,SLDH在后者也明显升高,且两组肝组织ATP酶及SDH活性明显降低。各染毒组尿LDH活性显著上升,DMF组及联合染毒r-GT活性显著降低,此两组肾脏组织AKP、ATP、SDH活性也明显降低。上述变化联合染毒组较单独作用组明显,因此认为DMF对肝肾具有损伤作用,乙醇可加重DMF的损伤作用。     

The Toxicity of Sterile Filtrate from Parodontal Pockets: (Section of Odontology)

The local effect of the absorption of toxic material from pyorrhœa pockets on the hard and soft tissues around the teeth is well known. In this experiment an attempt was made to study the toxic effect on remote structures by injecting the sterile filtrate fresh from pyorrhœa pockets into various animals.The filtrate was obtained from patients with chronic pyorrhœa by removing the contents from parodontal pockets and passing them through a Seitz filter. The sterile filtrate obtained was then injected into cats, guinea-pigs, rabbits, and rats, in varying amounts.In the group of four cats, all showed fatty degeneration of the liver and two showed extreme fatty degeneration of the kidney tubules.Five guinea-pigs receiving one injection of ½ c.c. of filtrate showed no pathological change in the liver or kidney. One out of three guinea-pigs receiving two injections of filtrate showed fatty degeneration of the liver, while five out of six pigs receiving one injection of 1 c.c.,—i.e. double the quantity—showed definite fatty degeneration of the liver. One out of two rabbits showed similar changes and of six rats injected, all died in from five to seven days.The experiment suggests that substances are elaborated in parodontal pockets which are highly toxic and tend to injure the liver and kidney of animals in the process of their elimination. Such toxic material proved fatal in fifteen of the twenty-five animals injected.     

Oxidative and nitrosative stress and apoptosis in the liver of rats fed on high methionine diet: Protective effect of taurine

ObjectiveThere are few reports about the direct toxic effects of hyperhomocysteinemia on the liver. We investigated oxidative and nitrosative stresses and apoptotic and necrotic changes in the liver of rats fed a high-methionine (HM) diet (2%, w/w) for 6 mo. We also investigated whether taurine, an antioxidant amino acid, is protective against an HM-diet–induced toxicity in the liver.MethodsLipid peroxide levels, nitrotyrosine formation, and non-enzymatic and enzymatic antioxidants were determined in livers of rats fed an HM diet. In addition, apoptosis-related proteins, proapoptotic Bax and antiapoptotic B-cell lymphoma-2 expressions, apoptotic cell count, histopathologic appearance in the liver, and alanine transaminase and aspartate transaminase activities in the serum were investigated.ResultsPlasma homocysteine levels and serum alanine transaminase and aspartate transaminase activities were increased after the HM diet. This diet resulted in increases in lipid peroxide and nitrotyrosine levels and decreases in non-enzymatic and enzymatic antioxidants in liver homogenates in rats. Bax expression increased, B-cell lymphoma-2 expression decreased, and apoptotic cell number increased in livers of rats fed an HM diet. Inflammatory reactions, microvesicular steatosis, and hepatocyte degeneration were observed in the liver after the HM diet. Taurine (1.5%, w/v, in drinking water) administration and the HM diet for 6 mo was found to decrease serum alanine transaminase and aspartate transaminase activities, hepatic lipid peroxide levels, and nitrotyrosine formation without any change in serum homocysteine levels. Decreases in Bax expression, increases in B-cell lymphoma-2 expression, decreases in apoptotic cell number, and amelioration of histopathologic findings were observed in livers of rats fed with the taurine plus HM diet.ConclusionOur results indicate that taurine has protective effects on hyperhomocysteinemia-induced toxicity by decreasing oxidative and nitrosative stresses, apoptosis, and necrosis in the liver.     

硫柳汞SD大鼠肌肉注射长期毒性研究

目的观察硫柳汞肌肉注射在大鼠体内的长期毒性反应的性质、程度,并确认靶器官。方法先进行硫柳汞在大鼠体内的最大耐受量(MTD)实验,由此设计长期毒性实验剂量,每组24只大鼠,肌肉注射,每周给药1次,共5周,停药恢复期为2周。观测给药期间动物的一般状况,并在末次给药后1周和停药恢复两周后解剖动物,进行血液学、生物化学和病理学检测,对实验结果统计分析,确认可能的毒性反应。结果硫柳汞大剂量(30mg/kg)肌肉注射可致大鼠双下肢给药部位肌肉硬结,肢体瘫痪,体重明显减轻,于第4次给药后濒临死亡;其肝功、肾功明显异常,血液系统紊乱;肺脏、肝脏、肾脏组织结构破坏严重;中枢神经系统和坐骨神经均可见空泡变性;心肌、胰、脾、肾上腺等脏器也有不同程度的损害。随着剂量的大幅降低,硫柳汞的毒性也明显减弱,与临床使用剂量相当时未见明显毒性反应。结论硫柳汞在较高剂量给药时可出现多脏器损害,特别是对中枢和外周神经及给药部位肌肉的损害较为严重,这种毒性反应随着剂量减小而降低。     

Effect of paraquat on plasma enzymes, insulin, glucose, and liver glycogen in the rat.

Paraquat dichloride was administered (45 mg/kg i.p.) to male Sprague-Dawley rats. The rats were sacrificed at different times after treatment. Blood was collected and plasma was used for various biochemical measurements. A significant increase in creatine phosphokinase activity was obtained at 12, 24, and 48 hr after paraquat treatment. The activities of glutamic oxaloacetic transaminase (GOT) and sorbitol dehydrogenase were also consistently elevated in paraquat-treated animals but a statistically significant increase was obtained only at 48 hr for GOT. Paraquat had no effect on glutamic pyruvic transaminase activity. Paraquat caused a marked increase in blood glucose and a marked depletion of liver glycogen that lasted for at least a period of 48 hr. The plasma insulin level in paraquat-treated animals was markedly depressed as compared to saline control. Various possibilities have been discussed for the hyperglycemic and liver glycogen-depleting effects of paraquat in the rat.     

Toxicity of oleic acid anilide in rats

In the present investigation, we have studied the toxic potential of oleic acid anilide (OAA) and heated oleic acid anilide (HOAA) in relation to the toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of OAA or HOAA in mineral oil by gavage, on alternate days for 2 weeks (total 7 doses). The control rats received an equal volume of mineral oil only. The animals were sacrificed at days 1, 7, and 28 following the last dose. Ratio of organ-to-body weight showed increases in spleen and kidney of HOAA and OAA treated rats, respectively, at day 1 while this ratio for liver in HOAA treated group showed a decrease at day 1. Among blood parameters, white blood cells increased in HOAA treated group at day 1 and in both OAA and HOAA groups at day 28. Mean corpuscular hemoglobin (MCH) and mean cell volume (MCV) also showed increases in the HOAA treated rats at days 7 and 28. Serum lactate dehydrogenase (LDH) decreased in both OAA and HOAA treated rats at day 1, while at day 7 the decrease was confined only to the HOAA group. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities also decreased at most of the time points. Liver mitochondrial ATPase activity decreased in the HOAA group at day 7 and in the OAA group at day 28. Among serum immunoglobulins, IgA levels increased throughout the study but the changes were more pronounced in HOAA treated rats. Splenic T-lymphocyte number decreased in the HOAA treated rats at day 1, recovered at day 7, and then showed an increase at day 28. The B-cell population remained steady at all time points. The T-helper and T-suppressor cell numbers in both OAA and HOAA groups decreased at day 1. However, at days 7 and 28, T-helper cell numbers increased in HOAA group, whereas T-suppressor cells showed an increase in both OAA and HOAA treated rats at day 28. The changes observed as a result of exposure to OAA and HOAA and more so by HOAA, further support that fatty acid anilides may play a role in the pathogenesis of TOS.     

复方决明子胶囊亚急性毒性研究

目的了解复方决明子胶囊的毒性。方法根据30 d喂养试验方法将大鼠分为阴性对照组及低、中、高3个剂量组。连续喂养30 d后,摘眼球采血作血常规及生化指标测定,取出肝、肾、脾、睾丸称重,并对肝、肾、脾、胃肠、睾丸、卵巢作组织病理学检查。结果各剂量组大鼠的体重及其增重、进食量、食物利用率与阴性对照组比较差异均无显著性(P>0.05);血红蛋白含量、红细胞计数、白细胞计数及白细胞分类均在正常值范围内;血清谷丙转氨酶、谷草转氨酶、尿素氮、肌酐、总胆固醇、甘油三酯、血糖、总蛋白、白蛋白测定值均在正常值范围内。大鼠的脏体比与阴性对照组比较,差异无显著性(P>0.05)。结论大鼠服用复方决明子胶囊30 d,对机体未见不良影响。     

Biochemical studies on nickel toxicity in weanling rats -- influence of vitamin C supplementation.

The influence of high intake of vitamin C in the young growing rats under administration of nickel sulphate in toxic doses has been studied. Ingestion of nickel sulphate depresses the growth rates of rats, alters the vitamin C status in different tissues, inhibits certain enzymes of vitamin C metabolism and changes the activities of alkaline phosphatase and succinic dehydrogenase in the liver and kidney tissues. The acid phosphatase activity of liver, kidney and brain tissues of rats and glucose-6-phosphatase activity in liver, and serum GOT activity were stimulated, with reduction in the in the liver GOT activity. There is stimulation in the activities of rat brain inorganic pyrophosphatase and cholinesterase. Kidney tissues of rats were found to be more susceptible towards nickel toxicity as compared to the hepatic tissues in respect of morphological alterations. There is almost no alteration in the hepatic lipid composition. Administration of vitamin C in high doses to rats fed nickel salts in toxic doses can restore not only the growth rates but also certain enzyme activities to a significant extent.     

Effect of ascorbic acid and vitamin E on biochemical changes associated with vitamin E deficiency in rats

Weanling male Sprague Dawley rats were fed a vitamin E and C-free basal diet with or without supplementation of 100 IU vitamin E per kg diet. After 20 weeks, the vitamin E-deficient rats were divided into four groups, six in each group, and received supplemental ascorbic acid and/or vitamin E by tube feeding daily for 7 days: Group I, 30 mg ascorbic acid/100 g body wt.; Group II, 0.03 mg RRR-alpha-tocopheryl acetate/100 g body wt.; Group III, 30 mg ascorbic acid and 0.03 mg RRR-alpha-tocopheryl acetate/100 g body wt.; and Group IV, placebo. The six control rats (Group V) received placebo. The rats were sacrificed, blood and liver samples were collected for biochemical determinations. Vitamin E deficiency significantly increased erythrocyte (RBC) spontaneous hemolysis, liver thiobarbituric acid (TBA) value, activities of glutamateoxaloacetate transaminase (GOT), pyruvate kinase (PK), and creatine phosphokinase (CPK) in plasma, and significantly lowered plasma vitamin E levels and glutathione peroxidase (GPX) activities. Tube-feeding ascorbic acid for 7 days produced partial reversal effect on liver TBA values, activities of plasma PK, GOT, CPK, and plasma vitamin E levels but not on RBC hemolysis and plasma GPX activity. Tube feeding both ascorbic acid and vitamin E showed similar partial reversal effect as feeding vitamin E alone on all the parameters stated above. The results suggest that ascorbic acid may spare the metabolism of vitamin E and partially reverse the changes in some of the biochemical parameters characteristic of vitamin E deficiency.