地高辛联合氨氯地平对大鼠肝微粒体细胞色素P450的影响

目的研究地高辛合用氨氯地平对大鼠肝脏组织药物代谢酶活性的影响,探讨两药合用后对药物代谢的影响,为临床合理用药提供理论依据。方法雄性大鼠40只,随机均分为空白对照、地高辛、氨氯地平、地高辛+氨氯地平组,每天给药1次,7d后处死。分别测定细胞色素P450和细胞色素b5含量,丙氨酸氨基转移酶、红霉素N-脱甲基酶、氨基比林N-脱甲基酶和7-乙氧基香豆素脱烃酶的活性。结果灌胃给药7d,地高辛、氨氯地平及联合用药对红霉素N-脱甲基酶活性均有明显抑制作用,联合用药的抑制作用未见增强。结论地高辛与氨氯地平合用对细胞色素P450酶系抑制作用未见增强。     

乙醇摄入对小鼠肝生物转化酶活性及抗氧化功能的影响

观察摄入乙醇（２．５ ｇ·ｋｇ－ １ ｐｏ,每日１ 次）后小鼠肝脏药物代谢酶活性及抗氧化功能的变化,为临床安全用药提供实验依据． 结果表明乙醇摄入４ 周内可诱导苯胺羟化酶,谷胱甘肽Ｓ－转移酶的活性,氨基比林脱甲基酶活性无明显变化,４ 周后则可使上述药酶活性下降,提示长期乙醇摄入对药物代谢的抑制性影响;乙醇摄入早期肝各抗氧化成分无明显改变,４ 周后,谷胱甘肽还原酶,谷胱甘肽过氧化酶,超氧化物歧化酶活性及谷胱甘肽含量逐渐下降,但过氧化氢酶活性明显升高,至第８ 周末下降,谷胱甘肽含量恢复正常,表明乙醇对肝抗氧化功能影响与摄入时间有关．     

肝损伤大鼠肝脏异物代谢功能的改变

目的　研究不同肝损伤状态下肝脏药物代谢和抗氧化功能的变化及规律 ,为肝纤维化患者的临床合理用药提供依据。方法　建立大鼠四氯化碳急性肝损伤和复合因素肝纤维化、肝硬化模型 ,差速离心法制备肝亚细胞组分 ,测定药物代谢酶和抗氧化酶活性。结果　不同肝损伤状态下大鼠肝微粒体药物代谢Ⅰ相酶———细胞色素P4 5 0 (CYP)总量、CYP1A1、3A活性和Ⅱ相酶—谷胱甘肽S 转移酶 (GST)活性均明显降低 ,随损伤时间递减 ,在肝硬化时达最低 ;而CYP2E1活性在急性肝损伤时即达最低 ,随染毒时间的延长而有所恢复。肝纤维化状态下CYP1A、CYP2E1、CYP3A和GST活性分别为正常对照组的 6 8%、5 6 %、81%和 5 9%。肝纤维化状态下胞浆抗氧化酶 GST、过氧化氢酶和谷胱甘肽过氧化物酶活性也呈不同程度降低 ,为正常对照组的 85 %、76 %和 5 4 %。结论　肝纤维化时 ,肝脏异物代谢酶功能降低 ,其降低程度多与肝损伤轻重和时间长短有关。     

妊娠大鼠肝微粒体药物代谢酶活性

<正> 为了解妊娠时肝脏对外源性化合物的生物转化能力是否发生改变,本文以苯胺羟化酶(ANH)及氨基比林N-脱甲基酶(AMD)活性为代表,系统研究了妊娠大鼠肝微粒体实行芳香化及N-脱甲基化作用的变化趋向. 成年未孕及妊娠12～14 d(中孕)和18～20 d(晚孕)♀Sprague-Dawley大鼠,按文献制备肝微粒体,测定药物代谢酶活性.结果表明,未孕大鼠肝微粒体细胞色素P450含量,b_5含量及NADPH-细胞色素c还原酶     

胸腺和性激素对大鼠肝脏脂质过氧化的调节作用(英文)

本文应用成年去胸腺或去性腺Wistar大鼠研究了胸腺对肝脏脂质过氧化(LPO)的影响及其与性激素有关的中间途径,结果表明,雌性成年去胸腺(ATx)大鼠肝匀浆丙二醛(MDA)含量增高,但雄性ATx大鼠肝脏MDA无明显变化;同时雌性ATx大鼠血浆雌二醇水平下降,雄性ATx大鼠血浆睾酮浓度降低,雌性大鼠卵巢切除术后肝脏MDA的变化与胸腺切除术后的变化相似,给予雌二醇可逆转去卵巢大鼠肝脏MDA的增高,在雄性大鼠中,无论是切除睾丸还是睾丸切除后补充睾酮对肝脏MDA均无明显影响,此外,给雌性ATx大鼠注射雌二醇可逆转其肝脏MDA的增高,这些结果提示胸腺在调节雌性大鼠肝脏抗氧化功能中起着重要作用,这种作用可能通过雌激素介导,因此我们设想在体内可能存在:胸腺-雌激素-肝脏通路”,它参与对肝脏抗氧化功能的调节。     

培氟沙星在对鼠肝微粒体酶系的抑制作用

大鼠经培氟沙星４００ｍｇ／ｋｇ，ｉｇ，ｑｄ×７ｄ后，肝微粒体酶系中的细胞色素ｂ５，氨基比林－Ｎ－脱甲基酶，７－乙氧基香豆素－Ｏ－脱乙基酶及苯并芘羟化酶含量显减少，细胞色素Ｃ还原酶活性降低，但细胞色素Ｐ－４５０，乙基吗啡－Ｎ－脱甲基酶，戊巴比妥侧链差化酶活性无改变。表明培氟沙星有抑制大鼠肝微粒体酶系中的一些酶的活性。     

吸烟所致宫内发育迟缓孕鼠肝脏药物代谢酶及抗氧化酶活性的变化

目的:研究和探讨吸烟所致宫内发育迟缓(IUGR)大鼠母体肝脏药物代谢酶活性和抗氧化功能的改变及其所带来的毒理学和药理学意义。方法:妊娠天数明确的Wistar大鼠16只,分为对照组和吸烟组。采用吸烟法建立大鼠IUGR模型,孕21d剖腹取胎,测量胎鼠生长发育指标(体重、身长、尾长)和胎盘重。差速离心法制备孕鼠肝亚细胞组分,测定多种药物代谢酶和抗氧化酶活性。结果:IUGR大鼠胎仔平均体重、身长、尾长、胎盘重都明显低于对照组,分别为对照组的87.7%、94.5%、95.3%和83.0%(P<0.01)。母体肝脏微粒体细胞色素P450(CYP)1A1活性升高,为对照组的137.9%(P<0.05);而CYP3A活性降低,为对照组的73.3%(P<0.05),谷胱甘肽S转移酶(GST)活性也降低,为对照组的86.5%(P<0.05)。母体肝脏胞浆超氧化物歧化酶(SOD)和过氧化氢酶(Cat)活性降低(P<0.05);谷胱甘肽过氧化物酶(GSHPx)活性升高,为对照组的1.11倍(P<0.05)。结论:孕期吸烟可致IUGR大鼠母体肝脏部分药物代谢酶活性和抗氧化系统功能改变,这些改变可能是导致IUGR发生的原因之一,同时吸烟可能改变孕期用药的疗效,增加药物毒性。     

培氟沙星对大鼠肝微粒体酶系的抑制作用

大鼠经培氟沙星４００ｍｇ／ｋｇ，ｉｇ，ｑｄ×７ｄ后，肝微粒体酶系中的细胞色素ｂ５、氢基比林－Ｎ－脱甲基醉，７－乙氧基香豆素－Ｏ－脱乙基酶及苯并芘羟化酶含量显著减少，细胞色素Ｃ还原酶活性降低，但细胞色素Ｐ－４５０、乙基吗啡－Ｎ－脱甲基酶、戊巴比妥侧链羟化酶活性无改变。表明培氟沙星有抑制大鼠肝微粒体酶系中一些酶的活性。     

肝纤维化状态下小肠药物代谢功能的改变

目的　探讨肝纤维化时小肠药物代谢功能的变化 ,为合理用药提供依据。方法　在大鼠肝纤维化模型上 ,测定小肠粘膜上皮细胞药物代谢酶、抗氧化酶及膜流动性变化 ,并与急性肝损伤、慢性肝硬化大鼠小肠相关指标进行比较。结果　与正常对照组相比 ,肝纤维化大鼠小肠粘膜上皮细胞药物代谢Ⅰ相酶红霉素N 脱甲基酶 (CYP3A)、7 乙氧异口恶唑O 脱乙基酶 (CYP1A1)和苯胺羟化酶 (CYP2E1)活性分别增加 2 .2 ,0 .6和 0 .3倍 ,而Ⅱ相酶葡糖醛酸转移酶 (UDPGT)和α 、π 谷胱甘肽S 转移酶 (GST)活性则分别减少 15 % ,4 3%和 5 7% ,同时膜脂质过氧化产物增加 ,抗氧化酶活性减弱 ,膜流动性降低。急性肝损伤时 ,上述指标无明显变化 ,而肝硬化时上述指标与肝纤维化组变化一致 ,并进一步增强。结论肝纤维化可影响小肠粘膜上皮细胞药物代谢功能 ,使Ⅰ相氧化功能增强 ,Ⅱ相结合反应减弱。小肠抗氧化功能降低可能与Ⅰ相氧化代谢增强有关。     

辐射对大鼠肝细胞色素P450氧化酶的影响

研究目的：辐射对大鼠肝细胞色素Ｐ４５０氧化酶（以下简称Ｐ４５０）的影响和辐射防护剂的防护作用。实验方法：雄性ＳＤ大鼠,设平行正常对照组、单独照射组和照前０５ｈ给ＷＲ２７２１（１００ｍｇ／只）组,每组５只动物。照射组大鼠１次接受６０Ｃｏγ射线７Ｇｙ全身照射,分别在照射后４ｈ、１,３,５ｄ处死,打开腹腔,用冷生理盐水进行肝原位灌流,取出肝脏,制成匀浆,用钙沉淀法制备肝微粒体。进行Ｐ４５０的光谱测定、氨基比林脱甲基酶活性、细胞色素ｂ５的光谱测定、体外直接照射肝微粒体蛋白后氨基比林脱甲基酶活性的测定。…     

The effects of reboxetine on autonomic and cognitive functions in healthy volunteers

RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor, causes autonomic and cognitive adverse events there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and autonomic functions with those of placebo in healthy humans. METHOD: A randomised, double-blind, crossover study of 12 healthy male volunteers aged 25 (21-27; median, range) years. Subjects orally received 4 mg reboxetine and placebo twice daily for periods of 14 days each with at least 14 days in between. Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation phase of VR (P<0.05). It did not affect cognitive functions such as flicker fusion frequency, choice reaction, memory and psychomotor coordination but increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic activation accounts for the prolongation of VR. The decrease of SCR and typical side effects suggest a relevant antimuscarinic drug action. Chronic administration of reboxetine at therapeutic doses causes autonomic dysfunction and subjective sedation but does not impair cognitive and psychomotor abilities in healthy humans.     

中医数学模型

中医五行学说数学模型是完全以中医理论为基础,以《黄帝内经》等古代医学文献为主要的参考资料进行归纳和整理的一种处理中医问题的有效方法。必要的数学假设,精练的数学语言对中医五行学说理论加以描述,并且初步建立起中医数学模型。同时为其他中医理论的数学建模提供了参考依据,从而逐步实现中医与现代科学接轨。     

扇贝裙边糖胺聚糖抗肿瘤作用和对荷瘤小鼠免疫功能的影响

目的：研究扇贝裙边糖胺聚糖（SS-GAG）的抗癌作用及对荷瘤小鼠免疫功能的影响。方法：建立小鼠移植性S180实体瘤模型，观察SS-GAG的抑瘤率以及对荷瘤小鼠的体质量、肝质量、白细胞计数、脾指数、胸腺指数的影响，同时观察SS-GAG对荷瘤小鼠细胞免疫活性的影响。结果：SS-GAG可明显抑制S180实体瘤的生长，SS-GAG与环磷酰胺联用可使化疗药物的抗癌作用增强并能有效提升减少的白细胞；能显著增强荷瘤小鼠腹腔巨噬细胞的吞噬能力和杀伤活性，增强荷瘤小鼠脾淋巴细胞的转化增殖和NK细胞活性。结论：SS-GAG可显著抑制肿瘤生长，与环磷酰胺联用时有减毒增效作用；并能增强荷瘤小鼠的免疫功能。     

颅骨修补对患者神经及认知功能的影响

目的 探讨颅骨修补对患者神经和认知功能的影响.方法 应用NIHSS卒中量表(美国国立卫生研究院卒中量表)对患者手术前后的神经功能进行评价,认知功能的评价采用MMSE量表(简明智能量表),结果进行t检验统计学分析.结果 NIHSS术前为(2.72±3.82),术后为(2.38±3.27),t检验P＜0.01.MMSE术前为(53.09±34.2),术后为(46.84±31.88),t检验P＜0.01.结论 颅骨修补可改善患者的神经功能障碍,提高患者的认知能力.除对开放性、污染伤口去除颅骨后需要延期修补外,对其他颅骨缺损的患者,一旦脑水肿消失,局部组织压力降低后就要考虑颅骨修补手术,以利于患者神经功能和认知能力的恢复.     

Effects of sertraline on autonomic and cognitive functions in healthy volunteers

Rationale Though sertraline, a selective serotonin reuptake inhibitor (SSRI), causes autonomic and cognitive adverse events such as dry mouth and somnolence, there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. Objective To compare the effects of sertraline on cognitive and autonomic functions with those of placebo in healthy humans. Method A randomized, double blind, cross over study of 12 healthy male volunteers aged 24 (21– 32; median; range) years. Subjects orally received 50 mg sertraline and placebo once daily for periods of 14 days each with at least 14 days in between. Heart rate variability (HRV), skin conductance level (SCL) and skin conductance response (SCR) following sudden deep respiration were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. Measurements were performed repeatedly before the start of drug administration and on the last treatment day. Results Sertraline caused a significant reduction of heart rate and SCL (P<0.05), whereas HRV and SCR were not changed. Cognitive functions such as flicker fusion frequency, memory, choice reaction time and psychomotor performance were not influenced by sertraline but slow and fast beta power density in the qEEG was increased. Conclusion Cognitive and psychomotor performance are not altered in healthy humans receiving multiple dosing with sertraline. The observed decreases in heart rate and SCL may be due to a sympatho-inhibitory effect of sertraline.     

ACEI治疗中老年高血压的疗效观察与分析

目的探讨血管紧张素转换酶抑制剂（ACEI）类药物治疗中老年高血压的临床特点及疗效。方法将确诊为原发性高血压患者118例，观察患者使用ACEI类药物治疗前后的血压、肾脏功能、心功能、代谢功能变化情况。结果ACEI治疗后，患者收缩压和舒张压（P〈0．01），24小时尿蛋白定量（P〈0．05），左室舒张末容积和左室收缩末容积（P〈0．05和P〈0．01）明显降低，左室射血分数和心输出量明显增加（P〈0．05），差异有统计学意义。治疗前后患者的血钾、血肌酐、血糖、血脂无明显变化。结论ACEI在有效降血压的同时，保护心脏、肾脏功能，对糖、脂代谢无影响，是临床理想的降压药物。     

Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis

BACKGROUND AND PURPOSE

Erectile dysfunction correlates with cardiovascular disease and its common risk factors due to the development of endothelial dysfunction. Positive effects on endothelial and erectile function have been described for substances inhibiting the renin-angiotensin-system. Here, we investigated in an atherosclerosis model, whether telmisartan (angiotensin receptor blocker) and ramipril (angiotensin converting enzyme inhibitor) are equivalent or the combination of both is superior in improving endothelial function in the aorta and the corpus cavernosum and in reducing atherosclerosis.

EXPERIMENTAL APPROACH

Wild-type (WT, C57/B6) and apolipoprotein-E-deficient (ApoE^−/−) mice were treated with a cholesterol-rich diet for 8 weeks. ApoE^−/− mice were supplemented with either telmisartan (20 mg·kg⁻¹·day⁻¹), ramipril (2.5 mg·kg⁻¹·day⁻¹) or the combination thereof.

KEY RESULTS

Systolic blood pressure significantly decreased in treatment groups (P < 0.001), with significantly smaller reduction under ramipril monotherapy (P < 0.05). Endothelial function (assessed by pharmacological stimulation of aortic rings and corpus cavernosum in organ bath chambers) was impaired in ApoE^−/− mice compared to WT animals, which was improved by all three treatments to a comparable extent (P < 0.05). Atherosclerotic lesion size in the ascending aorta and aortic sinus (P < 0.001), the amount of lipid peroxides in cavernosal and aortic tissue (P < 0.05) and free radical load (dihydroethidium-stain) (P < 0.05) were enhanced in untreated ApoE^−/− mice in comparison to WT animals and were significantly reduced by either treatment. In penile tissue, expression of eNOS could be restored by renin-angiotensin-aldosterone system blockade.

CONCLUSIONS AND IMPLICATIONS

Telmisartan and ramipril significantly improved endothelial function of aortic and cavernosal tissues in ApoE^−/− via reduction of oxidative stress. Combination of both agents does not enhance beneficial effects significantly.     

妇科术后辅助中药灌肠的临床效果观察

目的探讨中药灌肠对妇科术后肠功能恢复的临床研究。方法将妇科手术后24 h不能自行排气,明显腹胀排除机械性肠梗阻患者,给予中药低压保留灌肠。结果低压保留灌肠60例患者,30例用药6 h内,肛门排气,腹胀消失;29例用药24 h内肛门排气,腹胀消失;1例用药24 h仍未排气。结论采用中药低压保留灌肠:1增加肠蠕动,促进排气,解除腹胀,起到预防肠粘连的作用。2可使药液直接渗入病变部位,更有利于发挥药物的作用,达到加速炎症消除,渗出液的吸收,从而使肠壁水肿逐渐减轻,肠功能恢复。     

应用动态心电图分析心脏起搏器功能的价值

目的通过动态心电图（DCG）分析,了解起搏器起搏、感知及特殊功能,评价应用DCG检查在分析起搏器功能中的价值。方法回顾性分析180例次安装永久型心脏起搏器患者DCG检查结果。结果①检出起搏器起搏功能异常5例次,占2.8%。②检出起搏器感知功能异常60例次,占33.3%。③检出起搏器具有特殊功能65例次,占36.1%。④检出与起搏器有关心律失常52例次,占28.9%。结论 DCG检查能了解起搏器起搏、感知功能及起搏器特殊功能,判断与起搏器有关的各种心律失常,为通过体外程控仪调整起搏器技术参数提供参考依据。