Protective effect of ginger (Zingiber officinale) against PCB-induced acute hepatotoxicity in male rats

After absorption by the organism, polychlorinated biphenyls (PCBs) cross cellular membranes and pass into blood vessels and the lymphatic system. It is generally in the liver, adipose tissues, brain and skin that we find the strongest concentrations of PCBs. Herbal medicine remains as a discipline intended to treat and to prevent certain functional disorders and/or pathologies caused by oxidative stress, which can be induced by pesticides, medicines or pollutants. The objective of this study is to verify the toxic and oxidative effects of PCBs and to investigate the protective effect of ginger (Zingiber officinale) in the liver of male rats of the “Wistar” strain. These rats are divided into 6 groups: a control group (T), two groups treated with PCB at two different concentrations (P₁ and P₂), a group treated with ginger extract (G), a group pretreated with ginger extract and then injected with the first concentration of PCBs (P₁G), and a group pretreated with ginger and then injected with the second concentration of PCBs (P₂G). The results showed that the administration of PCBs led to an increase in the relative weight of the liver, and a significant increase in all of the hepatic biomarker levels (glucose, cholesterol, triglycerides, AST, ALT, and LDH) in the serum. Furthermore, an increase in the rate of lipid peroxidation and a decrease in the antioxidant enzyme activities (catalase, superoxide dismutase and glutathione peroxidase) were observed under the influence of PCBs in the liver. The histological test showed that the PCBs induced hepatocyte vacuolization, prominent and peripheralized nuclei, hepatocellular hypertrophy and turgor of the vein in the centriacinar regions. Pretreatment with ginger extract restored all of the biochemical and oxidative parameters to the normal values and reduced the injuries caused by the PCBs. In conclusion, in our experimental conditions, ginger effectively protects the liver against the hepatotoxic effects induced by PCBs.

After absorption by the organism, polychlorinated biphenyls (PCBs) cross cellular membranes and pass into blood vessels and the lymphatic system.     

Protective effects of lycorine against carbon tetrachloride induced hepatotoxicity in Swiss albino mice

Carbon tetrachloride (CCl(4)) is a well-known model for inducing chemical hepatic injury in Swiss albino mice. The present study was designed to examine the ability of lycorine a natural alkaloid compound to prevent CCl(4)-induced hepatotoxicity in the Swiss albino mice. After the experimental period of 8 weeks, CCl(4) significantly increased the generation of lipid peroxidation products, it reflected by high levels of malondialdehyde, hepatic marker enzymes like aspartate transaminase, Alanine transaminase, Lactate dehydrogenase, alkaline phosphatase and lipids profiles. These increases were accompanied by significant decreases of glutathione (GSH); vitamin C content and significant reduction in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and GSH reductase were observed in the mice liver, which were normalized by the lycorine treatment as compared with CCl(4)-induced group of mice. Moreover, the histological and ultrastructural observations evidenced that lycorine effectively rescues the hepatocyte from CCl(4)-induced oxidative damage without disturbing its cellular metabolic function and structural integrity. Therefore, lycorine may be considered a potent antioxidant against free radical-related diseases.     

Protective effect of type 2 diabetes on acetaminophen-induced hepatotoxicity in male Swiss-Webster mice

Type 2 diabetic (DB) mice exposed to CCl(4) (LD(50) = 1.25 ml/kg), acetaminophen (LD(80) = 600 mg/kg; APAP), and bromobenzene (LD(80) = 0.5 ml/kg) i.p. yielded 30, 20, and 20% mortality, respectively, indicating hepatotoxic resistance. Male Swiss-Webster mice were made diabetic by feeding high fat and administrating streptozotocin (120 mg/kg i.p.) on day 60. On day 71, time-course studies after APAP (600 mg/kg) treatment revealed identical initial liver injury in non-DB and DB mice, which progressed only in non-DB mice, resulting in 80% mortality. The hypothesis that decreased APAP bioactivation, altered toxicokinetics, and/or increased tissue repair are the underlying mechanisms was investigated. High-performance liquid chromatography analysis revealed no difference in plasma and urinary APAP or detoxification of APAP via glucuronidation between DB and non-DB mice. Hepatic CYP2E1 protein and activity, glutathione, and [(14)C]APAP covalent binding did not differ between DB and non-DB mice, suggesting that lower bioactivation-based injury is not the mechanism of decreased hepatotoxicity in DB mice. Diabetes increased cells in S phase by 8-fold in normally quiescent liver of these mice. Immunohistochemistry revealed overexpression of calpastatin in the newly dividing/divided cells, explaining inhibition of hydrolytic enzyme calpain in perinecrotic areas and lower progression of APAP-initiated injury in the DB mice. Antimitotic intervention of diabetes-associated cell division with colchicine before APAP administration resulted in 70% mortality in APAP-treated colchicine-intervened DB mice. These studies suggest that advancement of cells in the cell division cycle and higher tissue repair protect DB mice by preventing progression of APAP-initiated liver injury that normally leads to mortality.     

Protective effect of sulforaphane against dopaminergic cell death

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests oxidation of dopamine (DA) to DA quinone and consequent oxidative stress as a major factor contributing to this vulnerability. We have previously observed that exposure to or induction of NAD(P)H:quinone reductase (QR1), the enzyme that catalyzes the reduction of quinone, effectively protects DA cells. Sulforaphane (SF) is a drug identified as a potent inducer of QR1 in various non-neuronal cells. In the present study, we show that SF protects against compounds known to induce DA quinone production (6-hydroxydopamine and tetrahydrobiopterin) in DAergic cell lines CATH.a and SK-N-BE(2)C as well as in mesencephalic DAergic neurons. SF leads to attenuation of the increase in protein-bound quinone in tetrahydrobiopterin-treated cells, but this does not occur in cells that have been depleted of DA, suggesting involvement of DA quinone. SF pretreatment prevents membrane damage, DNA fragmentation, and accumulation of reactive oxygen species. SF causes increases in mRNA levels and enzymatic activity of QR1 in a dose-dependent manner. Taken together, these results indicate that SF causes induction of QR1 gene expression, removal of intracellular DA quinone, and protection against toxicity in DAergic cells. Thus, this major isothiocyanate found in cruciferous vegetables may serve as a potential candidate for development of treatment and/or prevention of PD.     

可乐定对常见有机磷农药中毒保护作用的实验研究

目的：研究传统的中枢性抗高血压药可乐定对常见有机磷农药中毒保护作用。方法：应用正交实验设计原理,选用L9（3^4)正交表,分别测试阿托品和可乐定对5种常见有机磷农药乐果、敌百虫、马拉硫磷、敌敌畏、甲胺磷染毒小鼠的身体震颤出现的时间、翻正反射消失的时间和存活时间的影响。结果：小鼠生存时间随有机磷农药染毒剂量的增加而缩短,有明显的剂量－效应关系。染毒前给予阿托品、可乐定明显延长小鼠的生存时间,以及延长小鼠中毒症状出现的时间。有机磷农药染毒后给予阿托品、可乐定,小鼠生存时间延长与否因农药而异,与其中毒作用迅速程度有关。结论：可乐定对有机磷农药中毒有较强的对抗作用,及早用药可显著延长中毒小鼠的生存时间。鉴于老药新用及与阿托品没的作用机制,在正确掌握指征及剂量情况下,完全可以在临床上使用。     

降钙素基因相关肽对全脑缺血脑组织的保护作用

目的:通过降钙素基因相关肽(calcitoningenerelatedpeptide,CGRP)对实验小鼠能量代谢的研究,进一步探讨CGRP对缺血脑组织的保护作用。方法:实验小鼠在缺血前给予CGRP,并在处死后测定缺血脑组织的三磷酸腺苷(ATP)和乳酸含量。ATP的测定采用虫荧光素-荧光素酶生物发光法;乳酸的测定采用对羟基联苯显色法。脑缺血模型的制作:采用小鼠断头缺血法。结果:CGRP对实验小鼠全脑缺血有明显的预防保护作用,表现为:CGRP可使缺血脑组织中乳酸水平减少,使ATP水平明显增加。而这种作用与给药剂量和给药方式有关,即在CGRP的剂量为2.67BU/g时效果较好,ATP为(5.4±2.3)pmol/g,乳酸为(1.4±0.4)mg/g,与模型组(2.6±1.3)pmol/g,(3.2±2.0)mg/g比,差异有显著性意义(P<0.05)。且随着给药时间的延长,缺血脑组织中乳酸水平降低更加明显(P<0.05),ATP水平显著增高(P<0.05)。CGRP对小鼠缺血脑组织的保护作用在超过一定剂量后无显著作用。结论:CGRP对全脑缺血小鼠有确切的预防保护作用,但应掌握合适剂量。     

氯胺酮对感染性休克大鼠保护作用的研究

目的　观察氯胺酮对感染性休克大鼠血流动力学、血浆肿瘤坏死因子α( TNFα)和白细胞介素 6 ( IL 6 )水平的影响 ,探讨其可能的抗休克机制。方法　取健康成年雄性 ( SD)大鼠 2 0只 ,采用盲肠结扎加穿孔 ( CL P)法复制败血症或感染性休克模型。随机分为假 CL P组、CL P组、氯胺酮 组和氯胺酮 组。假CL P和 CL P组术前 30 m in经股静脉持续输注生理盐水 5 ml· kg- 1· h- 1 ,氯胺酮 和氯胺酮 组分别输注氯胺酮 5 m g· kg- 1· h- 1和 10 m g· kg- 1· h- 1。经股动脉穿刺置管 ,持续监测平均动脉压 ( MAP)、心率 ( HR)及采集血样 ,应用酶联免疫吸附试验 ( EL ISA)检测血浆 TNFα和 IL 6水平。结果　 CL P组术后 MAP进行性下降 ,HR则先加快后减慢 ;血浆 TNFα和 IL 6水平明显升高。两种剂量的氯胺酮处理均能逆转 MAP和 HR下降 ,同时抑制血浆 TNFα和 IL 6水平升高 ,尤以氯胺酮 组作用更加明显。结论　氯胺酮对败血症或感染性休克大鼠具有明显的保护效应 ,其机制可能主要是拮抗促炎性细胞因子的产生     

黄芩苷对离体心脏缺血再灌注损伤的保护效应

目的:观察中药黄芩苷对离体状态下缺血再灌注损伤心脏的保护效应。方法:实验于2005-09/12在锦州医学院药理学教研室完成。选用雄性成年SD大鼠60只,头部击昏后迅速取出心脏,采用离体大鼠心脏Lan-gendorff灌流模型制备离体心脏缺血再灌注损伤模型。随机数字表法分为5组,每组12只。①对照组:以含氧K-H液灌注100min。②再灌注组:在对照组基础上灌注含氧K-H液10min后,停止灌流30min,然后再灌注60min。③黄芩苷60μmol/L再灌注组:灌注方法同再灌注组,再灌注时加入60μmol/L黄芩苷溶液。④黄芩苷120μmol/L再灌注组:再灌注时加入120μmol/L黄芩苷溶液。⑤黄芩苷240μmol/L再灌注组:再灌注时加入240μmol/L黄芩苷溶液。应用黄嘌呤测定法测定超氧化物歧化酶活性P应用TAB比色原理测定心肌组织中脂质过氧化产物丙二醛含量P收集各组冠脉流出液测定肌酸激酶、乳酸脱氢酶活性,用以评价心肌细胞受损程度及黄芩苷的保护作用。原位末端标记法标记后应用流式细胞仪进行细胞凋亡率测定,进一步从DNA水平观察细胞受损程度及黄芩苷的保护作用。计量资料差异比较采用t检验,组间数据处理采用方差齐性分析,采用非配对t检验。结果:在实验过程中无动物死亡,全部进入结果分析。①大鼠心肌组织超氧化物歧化酶活性:再灌注组较对照组明显下降[(7301±350),(3400±600)nkat/g,P<0.05];黄芩苷60,120,240μmol/L再灌注组较再灌注组有不同程度增加且随浓度增加作用增强[(5251±717),(5917±172),(6818±633),(3400±600)nkat/g,P<0.05]。②丙二醛含量:再灌注组较正常组增加[(85±17),(275±20)nmol/g,P<0.05],黄芩苷60,120,240μmol/L再灌注组较再灌注组有不同程度下降且呈剂量依赖性[(189±32),(126±27),(97±19),(275±20)nmol/g,P<0.05]。③冠脉流出液中肌酸激酶活性活性变化:再灌注组较正常组增加[(80.28±17.12),(105.43±3.95)mkat/L,P<0.05],黄芩苷60,120,240μmol/L再灌注组较再灌注组降低且有剂量依赖性[(90.86±9.13),(86.90±5.68),(84.40±19.15),(105.43±3.95)mkat/L,P<0.05]。④冠脉流出液中乳酸脱氢酶活性:再灌注组较正常组增加[(47.24±4.56),(68.59±11.74)mkat/L,P<0.05],黄芩苷60,120,240μmol/L再灌注组较再灌注组降低且有剂量依赖性[(50.45±5.37),(49.94±4.86),(47.57±4.58),(68.59±11.74)mkat/L,P<0.05]。⑤大鼠心肌细胞凋亡率:再灌注组较对照组凋亡率明显增加(10.58%,23.73%,P<0.05),黄芩苷60,120,240μmol/L再灌注组比再灌注组降低且呈剂量依赖性(9.35%,15.69%,10.41%,23.73%,P<0.05)。结论:黄芩苷可改善心肌缺血再灌注损伤所致乳酸脱氢酶、肌酸激酶释放量增加及心肌超氧化物歧化酶生成量的降低,降低乳酸脱氢酶、肌酸激酶、丙二醛释放量,增高超氧化物歧化酶活性;减少心肌细胞凋亡率。黄芩苷对离体心脏缺血再灌注所致损伤及凋亡有保护作用,并呈现剂量依赖性。     

黄芩苷对离体心脏缺血再灌注损伤的保护效应

目的：观察中药黄芩苷对离体状态下缺血再灌注损伤心脏的保护效应。方法：实验于2005-09／12在锦州医学院药理学教研室完成。选用雄性成年SD大鼠60只，头部击昏后迅速取出心脏，采用离体大鼠心脏Langendorff灌流模型制备离体心脏缺血再灌注损伤模型。随机数字表法分为5组．每组12只。①对照组：以含氧K-H液灌注100min。②再灌注组：在对照组基础上灌注含氧K-H液10min后，停止灌流30min，然后再灌注60min。③黄芩苷60μmol／L再灌注组：灌注方法同再灌注组，再灌注时加入60μmol／L黄芩苷溶液。④黄芩苷120μmol／L再灌注组：再灌注时加入120μmol／L黄芩苷溶液。⑤黄芩苷240μmol／L再灌注组：再灌注时加入240μmol／L黄芩苷溶液。应用黄嘌呤测定法测定超氧化物歧化酶活性；应用TAB比色原理测定心肌组织中脂质过氧化产物丙二醛含量；收集各组冠脉流出液测定肌酸激酶、乳酸脱氢酶活性，用以评价心肌细胞受损程度及黄芩苷的保护作用。原位末端标记法标记后应用流式细胞仪进行细胞凋亡率测定，进一步从DNA水平观察细胞受损程度及黄芩苷的保护作用。计量资料差异比较采用t检验，组间数据处理采用方差齐性分析，采用非配对t检验。结果：在实验过程中无动物死亡，全部进入结果分析。①大鼠心肌组织超氧化物歧化酶活性：再灌注组较对照组明显下降[（7301&;#177;350），（3400&;#177;600）nkat／g，P〈0.05]；黄芩苷60，120，240μmol／L再灌注组较再灌注组有不同程度增加且随浓度增加作用增强[（5251&;#177;717），（5917&;#177;172），（6818&;#177;633），（3400&;#177;600）nkat／g，P〈0．05]。②丙二醛含量：再灌注组较正常组增加[（85&;#177;17），（275&;#177;20）nmol／g，P〈0．05]，黄芩苷60，120，240μmol／L再灌注组较再灌注组有不同程度下降且呈剂量依赖性[（189&;#177;32），（126&;#177;27），（97&;#177;19），（275&;#177;20）nmol／g，P〈0．05]。③冠脉流出液中肌酸激酶活性活性变化：再灌注组较正常组增加[（80．28&;#177;17．12），（105．43&;#177;3．95）mkat／L，P〈0．05]，黄芩苷60，120，240μmol／L再灌注组较再灌注组降低且有剂量依赖性[（90．86&;#177;9．13），（86．90&;#177;5．68），（84．40&;#177;19．15），（105．43&;#177;3．95）mkat／L，P〈0．05]。④冠脉流出液中乳酸脱氢酶活性：再灌注组较正常组增加[（47．24&;#177;4．56），（68．59&;#177;11．74）mkat／L，P〈0．05]，黄芩苷60，120，240μmol／L再灌注组较再灌注组降低且有剂量依赖性[（50．45&;#177;5．37），（49．94&;#177;4．861，（47．57&;#177;4．58），（68．59&;#177;11．74）mkat／L．P〈0．05]。⑤大鼠心肌细胞凋亡率：再灌注组较对照组凋亡率明显增加（10．58％，23．73％，P〈0．05），黄芩苷60，120，240μmol／L再灌注组比再灌注组降低且呈剂量依赖性（9．35％，15．69％，10．41％，23．73％，P〈0．05）。结论：黄芩苷可改善心肌缺血再灌注损伤所致乳酸脱氢酶、肌酸激酶释放量增加及心肌超氧化物歧化酶生成量的降低，降低乳酸脱氢酶、肌酸激酶、丙二醛释放量，增高超氧化物歧化酶活性；减少心肌细胞凋亡率。黄芩苷对离体心脏缺血再灌注所致损伤及凋亡有保护作用，并呈现剂量依赖性。     

地奥心血康对急性脑缺血的保护作用

目的:观察由野生草本植物薯芋科的黄山药根茎中提取的甾体总皂甙精制而成的纯中药制剂地奥心血康对急性脑缺血损伤的保护作用。方法:实验于2004-03/2005-05在河南科技大学医学院机能学实验室完成。①选用昆明种小鼠130只,雄性。脑指数测定:选用65只小鼠,随机分为5组,每组13只:模型组,尼莫地平组用生理盐水灌胃,0.2mL/10g,连续7d;尼莫地平组术前尾静脉注射尼莫地平0.02mg/g(由山东新华制药股份有限公司生产,批号0300123,剂量10mL/支);地奥心血康低、高剂量组分别按0.5,1mg/g剂量灌胃2.5,5.0g/L地奥心血康溶液(成分原薯蓣总皂甙,剂量100mg/粒,由成都地奥制药集团有限公司生产,批号2304057),连续7d;正常组未造模,灌胃等量生理盐水,连续7d。②第8天,除正常组外其余小鼠麻醉后,结扎双侧颈总动脉和迷走神经,造成小鼠急性脑缺血模型。小鼠死后,取全脑,并计算脑指数(脑质量/体质量×100%)。大脑匀浆超氧化物歧化酶、谷胱甘肽过氧化物酶活性及丙二醛含量测定:其余小鼠分组及给药同“脑指数测定”。将除正常组小鼠外的52只麻醉后,结扎双侧颈总动脉10min后再灌注30min,然后断头取大脑皮质,制成匀浆,羟胺氧化法测定超氧化物歧化酶活性;硫代巴比妥酸法测定丙二醛含量;并用DTNB法测定谷胱甘肽过氧化物酶含量。③组间计量资料比较采用t检验。结果:小鼠130只均进入结果分析。①小鼠脑指数:尼莫地平组、地奥心血康高剂量组明显低于模型组(P<0.01);模型组明显高于假手术组(P<0.01);地奥心血康低剂量组与模型组相近。②小鼠脑匀浆超氧化物歧化酶和谷胱甘肽过氧化物酶活性:尼莫地平组和地奥心血康高剂量组明显高于模型组(P<0.01),模型组明显低于假手术组(P<0.01)。③小鼠脑匀浆丙二醛含量:尼莫地平组和地奥心血康高、低剂量组明显低于模型组(P<0.01),模型组明显高于假手术组(P<0.01)。结论:地奥心血康在急性脑缺血损伤过程中,通过清除氧自由基、抗氧化、减少脂质过氧化、阻断Ca2 内流等作用,减轻脑细胞的损伤,对脑组织细胞起保护作用。     

Protective effect of taurine against alendronate-induced gastric damage in rats

Alendronate (ALD) causes serious gastrointestinal adverse effects. The aim of this study was to investigate whether taurine (TAU), a semi-essential amino acid and an antioxidant, improves the alendronate-induced gastric injury. Rats were administered 20 mg/kg ALD by gavage for 4 days, either alone or following treatment with TAU (50 mg/kg, i.p.). On the last day of treatment, following drug administration, pylorus ligation was performed and 2 h later, rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined. Chronic oral administration of ALD induced significant gastric damage, increasing lipid peroxidation, MPO activity and collagen content, as well as decreasing tissue GSH levels. Treatment with TAU prevented the damage and also the changes in biochemical parameters. Findings of the present study suggest that ALD induces oxidative gastric damage by a local irritant effect, and that TAU ameliorates this damage by its antioxidant and/or membrane-stabilizing effects.     

Protective effect of lycopene against radiation-induced hepatic toxicity in rats

The radioprotective effect of lycopene against liver damage was investigated in 80 female Sprague Dawley rats (10 per group). Early-group rats included: controls (group 1), lycopene (group 2), radiotherapy alone (group 3), and lycopene + radiotherapy (group 4). Lycopene (5 mg/kg per day) was administered orally for 7 days; single-fraction 8 Gy abdominopelvic radiotherapy was administered on day 8. Early-group rats were sacrificed on day 10. Late-group rats (groups 5-8) underwent treatment with the same regimens but, in groups 6 and 8, lycopene was administered until all rats were sacrificed, 60 days postradiotherapy. Liver malondialdehyde levels increased significantly and glutathione (GSH) levels, GSH-peroxidase (GSH-Px) and superoxide dismutase (SOD) activity decreased significantly in radiotherapy versus control groups. In lycopene + radiotherapy groups, malondialdehyde levels decreased significantly and GSH levels, GSH-Px and SOD activity increased significantly compared with radiotherapy groups. No significant between-group histo pathological differences were observed in early groups; in late groups, histopathological changes increased significantly in the radiotherapy group versus control group. A significant decrease in histopathological changes occurred in the lycopene + radiotherapy group compared with the radiotherapy group. Lycopene supplementation significantly reduced radiotherapy-induced oxidative liver injury.     

镁离子对实验性脑损伤大鼠的脑保护作用

目的:探讨镁离子(Mg2+)对创伤性脑损伤的脑保护作用及其机制。方法:SD大鼠60只,随机分为空白组、对照组和试验组,参照Feeny法将对照组和试验组大鼠建立脑损伤模型,空白组大鼠仅行开颅手术。试验组于伤后30min腹腔注射100g/L硫酸镁600mg/kg,对照组则给予腹腔注射蒸馏水1.5mL,空白组不做任何处理。每组大鼠再按伤后处理时间再分为4小组,分别于伤后2,4,8和16h测定神经功能障碍计分(neurologicalseverityscore,NSS),然后处死,取损伤区脑组织测定脑组织中Mg2+,Ca2+,兴奋性氨基酸(excitatoryaminoacid,EAA)及血清中神经元特异烯醇化酶(neuronspecificenolase,NSE)的含量。结果:对照组大鼠伤后2h脑组织中Mg2+下降至(63.45±4.65)mg/g,而Ca2+和EAA分别升高至(97.35±4.79)mg/g和(24.64±5.86)moL/g,伤后8hNSE及NSS分别升高至(121.97±11.34)mg/L和(15.80±3.72)分,与空白组比较,差异有显著性意义(F=4.83～6.64,P<0.05)。应用硫酸镁干预后,试验组大鼠伤后2h脑组织中Mg2+升高至(89.76±7.38)mg/g,而Ca2+和EAA分别降低至(72.86±3.56)mg/g和(16.75±6.82)mmoL/g,伤后8hNSE及NSS分别降低至(83.31±9.25)mg/L和(11.03±3.87)分,与对照组比较,差异有显著性意义(F=4.96～7.72,P<0.05)。结论:原发性脑损伤可致脑组织中Mg     

17β雌二醇对大鼠坐骨神经损伤的保护

目的:探讨预先应用17β雌二醇对大鼠坐骨神经损伤的治疗作用,为周围神经损伤的临床治疗提供实验依据。方法:实验于2004-10/2005-08在锦州医学院实验室完成。选择成年雄性SD大鼠54只,随机数字表法分为3组,假手术组18只,仅暴露不损伤神经;手术对照组18只,制作坐骨神经钳夹伤模型;17β雌二醇处理组18只,损伤前1周给予17β雌二醇(1mg/kg)腹腔注射,1次/d。余二组在手术前1周仅腹腔注射同体积的蓖麻油,1次/d。①于术后2,4,7,14,21,28d进行坐骨神经功能指数评定,坐骨神经功能指数=-38.3(实验侧足印长度-正常侧足印长度)/正常侧足印长度 109.5(实验侧足印宽度-正常侧足印宽度)/正常侧足印宽度 13.3(实验侧足趾宽度-正常侧足趾宽度)/正常侧足趾宽度-8.8。坐骨神经功能指数以0为正常值,-100为神经完全离断指标。②术后7,14,28d各组取损伤近段坐骨神经甲苯胺蓝染色光镜下观察,醋酸铀和枸橼酸铅染色电镜下观察神经纤维超微结构。计算横断面单位面积的平均神经纤维个数和直径、轴突直径及髓鞘厚度。③术后7,14,21,28d各组大鼠取损伤近段坐骨神经进行S-100蛋白检测。结果:纳入动物54只,均进入结果分析。①假手术组术后2,28d坐骨神经功能指数值分别为-6.42和-5.71,差异无显著性意义。手术对照组和17β雌二醇处理组术后4,7,14,21d坐骨神经功能开始恢复,17β雌二醇处理组在术后21,28d坐骨神经功能指数值分别为-16.73和-16.14,而手术对照组在术后28d坐骨神经功能指数值为-16.32,可见17β雌二醇处理组大鼠功能恢复比手术对照组早1周左右。②光镜下观察术后14d17β雌二醇处理组损伤近段坐骨神经新生纤维较多,轴突直径较大且形状规则,纤维密度大、髓鞘较厚,明显高于手术对照组。术后28d手术对照组与17β雌二醇处理组变化基本一致,接近假手术组。③术后14d17β雌二醇处理组损伤近段坐骨神经电镜观察见大量新生神经纤维密集,许旺细胞包绕,轴突大小接近、形态均一,鞘内细胞器较多且清晰,明显优于手术对照组。术后28d手术对照组、17β雌二醇处理组新生神经纤维均基本成熟,差异不明显,已接近假手术组。④在周围神经损伤中S-100仅表达于许旺细胞中。术后14d17β雌二醇处理组阳性显色深且范围宽,与手术对照组比较差异有显著性意义。术后21,28d手术对照组与17β雌二醇处理组又无明显差异。结论:17β雌二醇能加速大鼠坐骨神经损伤后功能的恢复以及神经纤维的再生修复。     

褪黑激素对严重烧伤大鼠急性肺损伤的保护作用

目的：观察褪黑激素对烧伤大鼠肺组织氧化应激损伤和肺水肿的保护作用。 方法：实验于2005—03／11在青岛大学医学院完成。选用30只SD大鼠，随机分为对照组、烧伤组和褪黑激素组3组，每组10只。烧伤组和褪黑激素组大鼠麻醉后将背部皮肤置于沸水中15s造成30％Ⅲ度烫伤，伤后立即腹腔注射溶剂（体积分数为0．01的乙醇生理盐水）或褪黑激素10mg／kg，30min后腹腔注射15mL生理盐水复苏。对照组除背部浸入37℃水中且未补液外，其余同烧伤组。所有动物均于伤后6h断头处死，取出双肺测量以下指标：丙二醛和还原型谷胱甘肽含量，谷胱甘肽过氧化物酶、超氧化物歧化酶和髓过氧化物酶活性，以及肺质量（湿）／肺质量（干）比值。 结果：30只大鼠全部进入结果分析。①丙二醛含量：烧伤组显著高于对照组和褪黑激素组[（2．02&;#177;0．52），（1．39&;#177;0．36），（1．11&;#177;0．29）μmol／g，P〈0．01]，对照组和褪黑激素组间差异不显著。②还原型谷胱甘肽含量：烧伤组显著低于对照组和褪黑激素组[（7．42&;#177;1.01），（12．67&;#177;1．68），（11．18&;#177;1．63）μmol／g，P〈0．01]，褪黑激素组仍低于对照组（P〈0．05）。③烧伤组谷胱甘肽过氧化物酶和超氧化物歧化酶活性均低于对照组（P〈0．001，P〈0．01），而髓过氧化物酶活性比对照组高5．4倍（P〈0．001）。褪黑激素组谷胱甘肽过氧化物酶活性高于烧伤组（P〈0．01），髓过氧化物酶水平比烧伤组低21％（P〈0．05）。④肺质量（湿）／肺质量（干）比值：烧伤组显著高于对照组和褪黑激素组（4．42&;#177;0．51，3．57&;#177;0．64，3．98&;#177;0.15，P〈0．01，0．05），对照组和褪黑激素组间差异不显著。 结论：褪黑激素可明显抑制烧伤后肺组织氧化应激损伤和肺水肿，对烧伤早期急性肺损伤具有一定的保护作用。     

褪黑激素对严重烧伤大鼠急性肺损伤的保护作用

目的:观察褪黑激素对烧伤大鼠肺组织氧化应激损伤和肺水肿的保护作用。方法:实验于2005-03/11在青岛大学医学院完成。选用30只SD大鼠,随机分为对照组、烧伤组和褪黑激素组3组,每组10只。烧伤组和褪黑激素组大鼠麻醉后将背部皮肤置于沸水中15s造成30%Ⅲ度烫伤,伤后立即腹腔注射溶剂(体积分数为0.01的乙醇生理盐水)或褪黑激素10mg/kg,30min后腹腔注射15mL生理盐水复苏。对照组除背部浸入37℃水中且未补液外,其余同烧伤组。所有动物均于伤后6h断头处死,取出双肺测量以下指标:丙二醛和还原型谷胱甘肽含量,谷胱甘肽过氧化物酶、超氧化物歧化酶和髓过氧化物酶活性,以及肺质量(湿)/肺质量(干)比值。结果:30只大鼠全部进入结果分析。①丙二醛含量:烧伤组显著高于对照组和褪黑激素组[(2.02±0.52),(1.39±0.36),(1.11±0.29)μmol/g,P<0.01],对照组和褪黑激素组间差异不显著。②还原型谷胱甘肽含量:烧伤组显著低于对照组和褪黑激素组[(7.42±1.01),(12.67±1.68),(11.18±1.63)μmol/g,P<0.01],褪黑激素组仍低于对照组(P<0.05)。③烧伤组谷胱甘肽过氧化物酶和超氧化物歧化酶活性均低于对照组(P<0.001,P<0.01),而髓过氧化物酶活性比对照组高5.4倍(P<0.001)。褪黑激素组谷胱甘肽过氧化物酶活性高于烧伤组(P<0.01),髓过氧化物酶水平比烧伤组低21%(P<0.05)。④肺质量(湿)/肺质量(干)比值:烧伤组显著高于对照组和褪黑激素组(4.42±0.51,3.57±0.64,3.98±0.15,P<0.01,0.05),对照组和褪黑激素组间差异不显著。结论:褪黑激素可明显抑制烧伤后肺组织氧化应激损伤和肺水肿,对烧伤早期急性肺损伤具有一定的保护作用。     

17β雌二醇对大鼠坐骨神经损伤的保护

目的：探讨预先应用17β雌二醇对大鼠坐骨神经损伤的治疗作用，为周围神经损伤的临床治疗提供实验依据。方法：实验于2004-10／2005-08在锦州医学院实验室完成。选择成年雄性SD大鼠54只，随机数字表法分为3组，假手术组18只，仅暴露不损伤神经；手术对照组18只，制作坐骨神经钳夹伤模型；17β雌二醇处理组18只，损伤前1周给予17β雌二醇（1mg／kg）腹腔注射，1次／d。余二组在手术前1周仅腹腔注射同体积的蓖麻油，1次／d。①于术后2，4，7，14，21，28d进行坐骨神经功能指数评定，坐骨神经功能指数-38．3（实验侧足印长度-正常侧足印长度）／正常侧足印长度＋109．5（实验侧足印宽度-正常侧足印宽度）／正常侧足印宽度＋13．3（实验侧足趾宽度-正常侧足趾宽度）／正常侧足趾宽度-8．8。坐骨神经功能指数以0为正常值。-100为神经完全离断指标。②术后7，14，28d各组取损伤近段坐骨神经甲苯胺蓝染色光镜下观察，醋酸铀和枸橼酸铅染色电镜下观察神经纤维超微结构。计算横断面单位面积的平均神经纤维个数和直径、轴突直径及髓鞘厚度。③术后7，14，21，28d各组大鼠取损伤近段坐骨神经进行S-100蛋白检测。结果：纳入动物54只，均进入结果分析。①假手术组术后2，28d坐骨神经功能指数值分别为-6．42和-5．71，差异无显著性意义。手术对照组和17β雌二醇处理组术后4，7，14，21d坐骨神经功能开始恢复，17β雌二醇处理组在术后21，28d坐骨神经功能指数值分别为-16．73和-16．14，而手术对照组在术后28d坐骨神经功能指数值为-16．32，可见17β雌二醇处理组大鼠功能恢复比手术对照组早1周左右。②光镜下观察术后14d17β雌二醇处理组损伤近段坐骨神经新生纤维较多，轴突直径较大且形状规则，纤维密度大、髓鞘较厚，明显高于手术对照组。术后28d手术对照组与17β雌二醇处理组变化基本一致，接近假手术组。③术后14d17β雌二醇处理组损伤近段坐骨神经电镜观察见大量新生神经纤维密集，许旺细胞包绕，轴突大小接近、形态均一，鞘内细胞器较多且清晰，明显优于手术对照组。术后28d手术对照组、17β雌二醇处理组新生神经纤维均基本成熟，差异不明显，已接近假手术组。④在周围神经损伤中S-100仅表达于许旺细胞中。术后14d 17β雌二醇处理组阳性显色深且范围宽，与手术对照组比较差异有显著性意义。术后21，28d手术对照组与17β雌二醇处理组又无明显差异。结论：17β雌二醇能加速大鼠坐骨神经损伤后功能的恢复以及神经纤维的再生修复。     

龙胆苦甙对减轻乳鼠心肌缺血再灌注损伤的细胞研究

目的：观察龙胆苦甙（Gentiopicroside,GPS）后处理对离体心肌细胞缺血/再灌注损伤（ischemia and reperfusion injury,I/R）的拮抗作用及其可能的机制。方法采用SD大鼠乳鼠培养心肌原代细胞,用缺氧复氧模型模拟缺血再灌注（stimulated ischemia reperfusion,SI/R）。实验分为正常对照组（Control＋ScrambleRNA＋Veh）;缺氧复氧组（I/R＋ScrambleRNA＋Veh）;缺氧复氧＋龙胆苦甙后处理组（I/R＋ScrambleRNA＋GPS 组）以及缺氧复氧＋AktSiRNA＋龙胆苦甙后处理组（I/R＋AktSiRNA＋GPS）。采用化学法缺氧复氧模型,缺氧2 h,复氧4 h。复氧前给予GPS药物,检测心肌细胞乳酸脱氢酶（LDH）以及TUNEL染色确定心肌细胞的损伤程度以及抑制Akt表达后GPS的保护作用变化。结果与I/R＋ScrambleRNA＋Veh组相比,I/R＋ScrambleRNA＋GPS组LDH明显降低（P＜0.01）,TUNEL染色阳性率增加减少（P＜0.01）,Akt/Gsk3β信号通路磷酸化程度明显增加（P＜0.01）。与I/R＋ScrambleRNA＋GPS组相比,SI/R＋SiAktRNA＋GPS组,LDH活性显著增加（P＜0.01）,TUNEI染色阳性率增加（P＜0.01）,Gsk3β磷酸化程度减弱（P＜0.01）。结论 GPS后处理对I/R大鼠心肌具有保护作用,其作用机制与AKT/Gsk3β信号通路的活化有关。