银杏叶提取物对糖尿病大鼠一氧化氮水平的影响

目的研究银杏叶提取物(EGb)对糖尿病大鼠心肌、睾丸、脑组织一氧化氮水平的影响。方法用链脲佐菌素制备SD大鼠糖尿病模型。测定EGb对糖尿病大鼠心肌、睾丸、脑组织一氧化氮(NO)的含量及一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、结构型一氧化氮合酶(cNOS)的活性的影响。结果与正常组相比,糖尿病大鼠心肌、睾丸组织NO含量及NOS、iNOS活性升高,脑组织NO含量及NOS活性升高。与糖尿病组相比,EGb治疗组大鼠心肌、睾丸组织NO含量及NOS、iNOS活性下降。结论EGb能够对抗糖尿病大鼠过量NO对心肌、睾丸组织的损伤。     

银杏叶提取物对糖尿病大鼠一氧化氮水平的影响

目的 研究银杏叶提取物(EGb)对糖尿病大鼠心肌、睾丸、脑组织一氧化氯水平的影响。方法用链脲佐菌素制备SD大鼠糖尿病模型。测定EGb对糖尿病大鼠心肌、睾丸、脑组织一氧化氯(NO)的含量及一氧化氯合酶(NOS)、诱导型一氧化氯合酶(iNOS)、结构型一氧化氯合酶(cNOS)的活性的影响。结果与正常组相比，糖尿病大鼠心肌、睾丸组织NO含量及NOS，iNOS活性升高，脑组织NO含量及NOS活性升高。与糖尿病组相比，EGb治疗组大鼠心肌、睾丸组织NO含量及NOS、iNOS活性下降。结论 EGb能够对抗糖尿病大鼠过量NO对心肌、睾丸组织的损伤。     

Wistar大鼠肺组织内NOS阳性细胞分布及其意义

目的 :探讨NO在肺组织内的自身生理功能、病理生理过程中的可能作用及其临床意义。方法 :采用NADPH d黄递酶组化法观察了成年Wistar大鼠肺组织内NOS阳性细胞的分布。结果 :在支气管粘膜上皮中发现有NOS阳性细胞 ,其分布在气管、支气管、细支气管、终末细支气管和呼吸性细支气管 ,并以后两者数量较多。结论 :肺内存在有NOS阳性细胞 ,并有可能在临床治疗中发挥作用。     

顺铂染毒大鼠睾丸定量组织学分析及睾丸酶活力的变化

目的 探讨顺铂(CP)染毒大鼠睾丸组织病理学和睾丸酶活力的变化。方法 选择健康成年雄性Wistar大鼠,随机分为CP 1.0、2.5和5.0 mg/kg组及对照组,连续腹腔注射染毒3 d。染毒结束后,制备PAS(Periodic AcidSchiff)染色病理切片,观察睾丸组织病理变化并行定量组织学分析。分光光度法测定琥珀酸脱氢酶(SDH)、苹果酸脱氢酶(MDH)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)、诱导型一氧化氮合酶(i NOS)和Na+-K+-ATPase活力。实时荧光定量PCR检测i NOS和Na+-K+-ATPasemRNA表达水平。结果 CP染毒后大鼠睾丸组织病理学改变主要见于睾丸生精上皮精子发生周期第Ⅱ-Ⅲ期。定量组织学分析发现,在生精上皮第Ⅱ-Ⅲ期CP 2.5和5.0 mg/kg组大鼠睾丸生精小管相对面积和直径变小,管腔相对面积增加(P<0.05)。CP各剂量组生精上皮占生精小管面积百分比和生精小管管腔直径均变小(P<0.05),CP5.0 mg/kg组睾丸间质血管面积增加(P<0.01)。与对照组比较,CP 5.0 mg/kg组精子数减少,精子活力降低(P<0.05)。CP各染毒组SDH活力均低于对照组,而MDH和i NOS活力仅5.0 mg/kg组低于对照组(P<0.05)。CP 5.0 mg/kg组ACP、AKP和Na+-K+-ATPase活力均明显高于对照组(P<0.05)。RT-PCR结果显示,Na+-K+-ATPase和i NOS mRNA表达水平与酶活力改变一致。结论 顺铂可能参与改变睾丸细胞能量代谢相关酶活力而致睾丸细胞损伤。     

归芪五子方对睾丸损伤模型大鼠精子凋亡以及SOD和MDA与NOS水平的影响

目的观察归芪五子方对汽油尾气所致睾丸损伤模型大鼠精子凋亡率、睾丸组织超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮合酶(NOS)水平的影响。方法以气管滴定法复制汽油尾气睾丸损伤模型,并给予归芪五子方治疗,检测大鼠精子凋亡率及睾丸组织SOD、NOS、MDA水平。结果归芪五子方大剂量组精子凋亡率显著低于模型组(P<0.05);与模型组比较,归芪五子方大剂量组大鼠睾丸组织SOD水平显著升高,NOS、MDA水平降低,差异有统计学意义(P<0.05)。结论归芪五子方对汽油尾气所致睾丸损伤模型大鼠精子凋亡有一定抑制作用,机制可能为减少大鼠睾丸组织内自由基生成,提高其抗自由基能力。     

苦碟子注射液对青春前期大鼠睾丸扭转复位健侧睾丸的远期影响

目的探讨苦碟子注射液对青春前期大鼠睾丸扭转复位后健侧睾丸的远期影响及其保护作用。方法将32只4周龄健康SD6大鼠随机分为4组：假手术组、模型组、苦碟子单次给药组和苦碟子连续给药组,每组8只。建立单侧睾丸扭转复位动物模型,术后8周取健侧睾丸,计算睾丸系数,检测睾丸组织总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）、一氧化氮合酶（N0s）活性与丙二醛（MDA）含量,行睾丸组织病理学观察。结果与假手术组比较,模型组SOD、T-AOC、NOS活性均下降,MDA含量升高（P〈0．05）。与模型组比较,连续给药组SOD、T—AOC、NOS活性均升高,MDA含量下降妒〈0．05）。模型组可见生精小管退变,间质出现水肿,2个给药组使睾丸扭转复位诱发的组织学改变明显改善。结论青春前期大鼠单侧睾丸扭转复位后可致健侧睾丸缺血再灌注损伤,苦碟子注射液可通过有效清除氧自由基,抑制脂质过氧化反应,对青春前期大鼠睾丸扭转复位后健侧睾丸损伤远期效果具有一定的保护作用,且连续给药明显优于单次给药。     

烟草烟雾染毒小鼠精子形态和睾丸某些生化指标的变化北大核心CSCD

目的观察烟草烟雾染毒对小鼠精子畸形率及睾丸组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、酸性磷酸酶(ACP)、乳酸脱氢酶(LDH)和一氧化氮合成酶(NOS)活性的影响。方法每只雄鼠计数500条完整的精子,计算出精子畸形率;用分光光度法检测小鼠睾丸组织中SOD、MDA、ACP、LDH和NOS的活性。结果小鼠精子畸形率随着染毒时间的延长而增加,烟草烟雾染毒可引起小鼠睾丸组织匀浆中SOD、MDA和NOS活性显著升高,ACP和LDH活性显著下降。结论烟草烟雾染毒可致小鼠精子形态和睾丸某些生化指标发生变化。     

黄芪提取物对全脑缺血损伤的保护作用

目的　研究黄芪提取物 (EA )对大鼠和小鼠全脑缺血的保护作用。方法　采用小鼠双侧颈总动脉结扎法 ,造成全脑急性缺血模型 ,观察小鼠 12h内存活时间 ,并记录 2、6、12h小鼠死亡率。参照Pulsinelli法制作大鼠全脑缺血再灌注模型 ,观察EA的神经保护作用 ,记录脑电图 (EEG) ,观察并记录大鼠全脑缺血后翻正反射 (rightingreflex ,RR )恢复时间 ,测定脑组织中谷胱甘肽过氧化物酶 (GSH Px)、乳酸脱氢酶 (LDH)、一氧化氮合酶 (NOS)活性 ,测定组织中诱导型NOS(iNOS)的表达并运用图像分析系统定量分析海马区平均光密度值 (meanopticaldensity ,MOD)。 结果　EA能降低急性脑缺血小鼠的死亡率 ,延长 12h内小鼠存活时间。EA能促进大鼠EEG和翻正反射的恢复 ,可显著提高全脑缺血再灌注大鼠脑组织中GSH Px、LDH活性 ,降低NOS活性 ,抑制海马iNOS的表达 ,降低其MOD值。结论　黄芪提取物对大鼠和小鼠全脑缺血损伤具有保护作用     

烟草烟雾染毒小鼠精子形态和睾丸某些生化指标的变化

目的观察烟草烟雾染毒对小鼠精子畸形率及睾丸组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、酸性磷酸酶(ACP)、乳酸脱氢酶(LDH)和一氧化氮合成酶(NOS)活性的影响。方法每只雄鼠计数500条完整的精子,计算出精子畸形率;用分光光度法检测小鼠睾丸组织中SOD、MDA、ACP、LDH和NOS的活性。结果小鼠精子畸形率随着染毒时间的延长而增加,烟草烟雾染毒可引起小鼠睾丸组织匀浆中SOD、MDA和NOS活性显著升高,ACP和LDH活性显著下降。结论烟草烟雾染毒可致小鼠精子形态和睾丸某些生化指标发生变化。     

弥漫性颅脑损伤对大鼠海马一氧化氮合成酶活性及表达的影响

目的 :研究大鼠弥漫性颅脑损伤后海马结构一氧化氮合成酶 (NOS)活力及表达 ,分析海马不同亚区NOS活力变化与时间的关系。方法 :制作Wistar大鼠弥漫性脑损伤模型 ,并分对照组、假手术组及伤后6、12、24、48h组 ,于不同时间点获取脑组织 ;用NADPH 黄递酶 (NADPH d)组织化学法和免疫组化法检测NOS的活性及表达情况。结果 :NADPH d组织化学法显示 ,弥漫性脑损伤后 ,海马结构NOS阳性神经元数量在伤后6h最多 ,以后逐渐减少 ,伤后24、48h组明显低于假手术组 (P<0 05) ;免疫组化结果显示 ,在CA1、CA3区和齿状回 (DG) ,伤后24、48h组阳性细胞数均低于假手术组 (P<0 01)。结论 :大鼠弥漫性脑损伤后 ,可引起海马各区NOS的变化 ,该变化可能是造成脑组织继发性损害机制之一。     

Particle distribution in lung and lymph node tissues of rats and dogs and the migration of particle-containing alveolar cells in vitro

Whole rat lungs and individual dog lung lobes were instilled either with low numbers (10(7)) or high numbers (10(9)) of fluorescent polystyrene microspheres (PLM), or with saline alone. Particle distributions in dog and rat lung lobes and tracheobronchial lymph nodes (TBLN) were studied up to several weeks after particle instillations using methacrylate-embedded tissues and epifluorescence light microscopy. Free alveolar cells were obtained from rats and dogs by lung lavage 1 or 7 d after particle instillations. Lavaged cells were tested for directed migration toward the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP). Random migration in the absence of the FMLP was used as a control. The dog lung interstitium contained many more particles than did the rat lung interstitium, and particle numbers in interstitial and TBLN cells of dogs were higher than in those of rats. FMLP enhanced the number of migrating cells about twofold. Increasing particle numbers in lavaged phagocytes (greater than 10 particles/phagocyte in dogs; greater than 20 particles/phagocyte in rats) decreased their ability to migrate. The higher fractions of particles in the dog lung interstitium are thought to be an important reason for prolonged retention and increased TBLN transport of deposited particles in dogs as compared with rats. Our results suggest that cell mobility is lost after ingestion of high numbers of particles, and that this occurs earlier with dog than with rat lung cells.     

Species and tissue differences in the microsomal oxidation of 1,3-butadiene and the glutathione conjugation of butadiene monoxide in mice and rats. Possible role in 1,3-butadiene-induced toxicity.

Rat and mouse liver, lung, and kidney microsomes metabolized 1,3-butadiene to butadiene monoxide (BM), whereas microsomes from testis, one of the target organs of 1,3-butadiene toxicity in both species, were ineffective. 1,3-Butadiene metabolism was NADPH-dependent and inhibited by 1-benzylimidazole. With mouse microsomes, a 4-fold higher rate was measured with kidney compared with liver or lung, which exhibited similar rates. With rat microsomes, the rate obtained with liver was 2- and 6-fold higher than those of lung and kidney, respectively. Overall, oxidation rates by mouse tissues were higher than those of rat tissues. These results, along with the finding that BM was stable in the presence of rat plasma, provide evidence for the role of circulating metabolites in 1,3-butadiene-induced toxicity. Furthermore, crotonaldehyde, a known carcinogen, was detected with mouse tissues only. Thus, in addition to the greater ability of mouse tissues to produce BM, formation of crotonaldehye may contribute to the greater susceptibility of mice to 1,3-butadiene toxicity compared with rats. Nearly all rat liver glutathione S-transferase activity was localized to the cytosol (greater than 96%). BM glutathione conjugation rates with liver cytosol of both species were similar, whereas conjugation rates with mouse lung and kidney cytosol were 4- and 2-fold higher than those of rat lung and kidney, respectively. Thus, species differences in BM glutathione conjugation do not correlate with species susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)     

雄激素对大鼠主动脉一氧化氮合酶/一氧化氮体系的调节

目的：研究雄激素对大鼠主动脉一氧化氮合酶／一氧化氮(NOS／NO)体系的影响，以探讨雄激素对心血管系统的作用。方法：将30只雄性大鼠随机分为三个组，每组10只，去卵巢组(A组)、去卵巢 雄激素组(B组)、假手术组(C组)。正常饮食2个月后处死大鼠，测血清雄激素、主动脉匀浆一氧化氮合酶活性及一氧化氮含量。结果：同假手术组相比。去势大鼠主动脉匀浆NOS活性及NO含量显著降低，在补充适量的雄激素后．主动脉匀浆NOS活性及NO含量显著上升。结论：雄激素可以调节大鼠动脉内一氧化氮合酶／一氧化氮体系，可能是其调节血管张力的作用机制。     

Species differences between rats and mice in the teratogenic action of ethylenethiourea: in vivo/in vitro tests and teratogenic activity of sera using an embryonic cell differentiation system

In vivo/in vitro studies on rats showed that ethylenethiourea inhibited the differentiation of midbrain cells more severely than that of limb bud cells. In in vitro studies using midbrain cell cultures, ethylenethiourea concentrations inhibited the production of differentiated foci by 50% in mouse cells, a rate 11-fold higher than that in rat cells. Differentiation of rat midbrain cells was also inhibited by the serum samples prepared from rats or mice dosed with up to 200 mg/kg of ethylenethiourea. However, differentiation of mouse cells was not inhibited by these animal serum samples. The concentration of ethylenethiourea in rat sera was only 2-fold higher than that in mice sera at 2 hr after dosing with 200 mg/kg. Therefore, the different sensitivity of the midbrains of these two species may be one reason that ethylenethiourea is teratogenic in rats but not in mice.     

Comparison of biliary excretion of organic anions in mice and rats

Biliary excretion of cholephilic organic acids in anesthetized, male Swiss-Webster mice was compared to that in male Sprague-Dawley rats. The mouse excreted six of the eight compounds examined at a faster or equal rate than the rat. Indocyanine green, rose bengal, phenol-3,6-dibromsulphthalein disulfonate, and eosine were excreted in mice at a rate 120 to 460% higher than in rats. The excretion rates of bromcresol green and sulfobromophthalein glutathione conjugate were similar in the two species, whereas amaranth was excreted at a slightly lower rate in mice than in rats. Biliary excretion of sulfobromophthalein (BSP), especially its glutathione conjugate, was significantly lower in the mouse which corresponded to a difference in BSP-glutathione transferase activities between the two species (mouse, 0.97; rat, 1.35 μmol/min/g liver). The depression of bile production by cholestatic organic anions was stronger, and the stimulation of bile flow by choleretic acids was weaker in mice than in rats. Differences in biliary bile acid excretion (mouse, 3.62; rat, 1.42 μmol/kg/min), bile flow (mouse, 102; rat, 69 μl/kg/min), and liver weight (mouse, 57; rat, 38 g/kg) but not hepatic ligandin concentration (mouse, 132; rat, 214 nmol BSP/g liver) may explain the variations in the biliary organic anion excretion between mice and rats.     

钩藤碱对缺血-再灌注大鼠脑NOS变化的作用

目的：研究钩藤碱（Ｒｈｙ）对大鼠脑缺血－再灌注皮层和海马一氧化氮合酶（ＮＯＳ）变化的作用。方法：阻断大鼠双侧颈总动脉１５ｍｉｎ和再灌注２４ｈ建立脑缺血－再灌注损伤模型,用ＮＡＤＰＨ－ｄ组化技术检测脑ＮＯＳ阻性细胞数目的变化和Ｒｈｙ的影响。结果：脑缺血－再灌注２４ｈ后,皮层和海马ＮＯＳ阳性细胞数目显著增多,Ｒｈｙ（１２．５和２５ｍｇ／ｋｇ）缺血前３０ｍｉｎ腹腔注射,可显著抑制此增多,与ＮＯＳ拮抗剂Ｌ     

Effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of phytoestrogens

The effect of breast cancer resistance protein (Bcrp/Abcg2) on the disposition of the phytoestrogens daidzein, genistein, and coumestrol was investigated using Bcrp(-/-) mice. Expression of the genes for either mouse Bcrp or human BCRP in MDCK II cells induced apically directed transport of the three phytoestrogens, whereas their transcellular transport was identical in mock and LLC-PK1 cells expressing mouse Mdr1a. After oral administration, the plasma levels of daidzein and genistein were increased in Bcrp(-/-) mice, but only a minimal change was observed for coumestrol. At steady state, tissue-to-plasma concentration ratios of the three phytoestrogens in the brain and testis of wild-type mice were very small and similar to those of [(14)C]inulin, whereas those were significantly increased in the brain and testis of Bcrp(-/-) mice. The largest increases were observed with genistein (9.2- and 5.8-fold in the brain and testis, respectively). The distributions of genistein in the epididymis and fetus, but not the ovary, were also increased in Bcrp(-/-) mice. The Bcrp protein was localized in the luminal membrane of the endothelial cells in the testis and the body of the epididymis and in both the luminal and abluminal side of ducts in the head of the epididymis. These results suggest that Bcrp limits the oral availability and distribution into the brain and testis, epididymis, and fetus of phytoestrogens.     

Transgenic mouse lines expressing rat AH receptor variants — A new animal model for research on AH receptor function and dioxin toxicity mechanisms

Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity mainly because of their mutated aryl hydrocarbon receptor (AHR) gene. In H/W rats, altered splicing of the AHR mRNA generates two AHR proteins: deletion (DEL) and insertion (INS) variants, with the INS isoform being predominantly expressed. To gain further insight into their functional properties, cDNAs of these and rat wild-type (rWT) isoform were transferred into C57BL/6J-derived mice by microinjection. The endogenous mouse AHR was eliminated by selective crossing with Ahr-null mice. A single mouse line was obtained for each of the three constructs. The AHR mRNA levels in tissues were generally close to those of C57BL/6 mice in INS and DEL mice and somewhat higher in rWT mice; in testis, however, all 3 constructs exhibited marked overexpression. The transgenic mouse lines were phenotypically normal except for increased testis weight. Induction of drug-metabolizing enzymes by TCDD occurred similarly to that in C57BL/6 mice, but there tended to be a correlation with AHR concentrations, especially in testis. In contrast to C57BL/6 mice, the transgenics did not display any major gender difference in susceptibility to the acute lethality and hepatotoxicity of TCDD; rWT mice were highly sensitive, DEL mice moderately resistant and INS mice highly resistant. Co-expression of mouse AHR and rWT resulted in augmented sensitivity to TCDD and abolished the natural resistance of female C57BL/6 mice, whereas mice co-expressing mouse AHR and INS were resistant. Thus, these transgenic mouse lines provide a novel promising tool for molecular studies on dioxin toxicity and AHR function.     

Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 2: species differences in response.

Thiamethoxam is a neonicotinoid insecticide that is not a mutagen, but it did cause a significant increase in liver cancer in mice, but not rats, in chronic dietary feeding studies. Previous studies in mice have characterized a carcinogenicity mode of action that involved depletion of plasma cholesterol, cell death, both as single cell necrosis and as apoptosis, and sustained increases in cell replication rates. In a study reported in this article, female rats have been exposed to thiamethoxam in their diet at concentrations of 0, 1000, and 3000 ppm for 50 weeks, a study design directly comparable to the mouse study in which the mode of action changes were characterized. In rats, thiamethoxam had no adverse effects on either the biochemistry or histopathology of the liver at any time point during the study. Cell replication rates were not increased, in fact they were significantly decreased at several time points. The lack of effect on the rat liver is entirely consistent with the lack of liver tumor formation in the two-year cancer bioassay. Comparisons of the metabolism of thiamethoxam in rats and mice have shown that concentrations of the parent chemical were either similar or higher in rat blood than in mouse blood in both single dose and the dietary studies strongly indicating that thiamethoxam itself is unlikely to play a role in the development of liver tumors. In contrast, the concentrations of the two metabolites, CGA265307 and CGA330050, shown to play a role in the development of liver damage in the mouse, were 140- (CGA265307) and 15- (CGA330050) fold lower in rats than in mice following either a single oral dose, or dietary administration of thiamethoxam for up to 50 weeks. Comparisons of the major metabolic pathways of thiamethoxam in vitro using mouse, rat, and human liver fractions have shown that metabolic rates in humans are lower than those in the rat suggesting that thiamethoxam is unlikely to pose a hazard to humans exposed to this chemical at the low concentrations found in the environment or during its use as an insecticide.