溃疡性结肠炎模型的构建及其炎症反应机制研究

目的：构建2,4,6-三硝基苯磺酸（2,4,6-trinitrobenzene sulfonic acid,TNBS）以及恶唑酮（oxazolone,OXZ）诱导的小鼠溃疡性结肠炎（ulcerative colitis,UC）模型。方法：120只昆明小鼠（）随机分为4组（n=30）。Ⅰ组、Ⅱ组参照Morris及Walter的方法制备小鼠TNBS模型：Ⅰ组（TNBS溶剂对照组）,50%乙醇0.1 m L灌肠;Ⅱ组（TNBS模型组）,0.6%TNBS溶液0.1 m L灌肠;两组灌肠给药一次后在d 1、d 2、d 3、d 5、d 7每组处死6只。Ⅲ组、Ⅳ组参照Heller方法制备小鼠OXZ模型：Ⅲ组（OXZ溶剂对照组）,皮肤涂抹100%乙醇0.1 m L,每天一次,连续2 d,d 7以50%乙醇0.1 m L灌肠;Ⅳ组（OXZ模型组）,皮肤涂抹1%OXZ溶液（100%乙醇溶解）0.1 m L每天一次,连续2 d（致敏）,d 7以0.5%OXZ（50%乙醇溶解）0.1 m L灌肠;两组灌肠给药一次后在d 1~d 5每天处死6只小鼠。观察Ⅰ~Ⅳ组小鼠疾病活动指数（disease activity index,DAI）、结肠组织大体损伤指数（colon macroscopic damage index,CMDI）和病理组织学评分（histopathological score,HPS）,并检测小鼠结肠组织中髓过氧化物酶（myeloperoxidase,MPO）、白细胞介素-4（interleukin-4,IL-4）、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的水平。结果：两种模型组小鼠DAI,CMDI和HPS均较对照组有明显改变;TNBS和OXZ诱导的结肠炎均可导致MPO明显上升,TNBS结肠炎TNF-α明显上升,OXZ结肠炎IL-4明显下降。结论：TNBS及OXZ均能诱导小鼠溃疡性结肠炎模型。两种模型各有特点,其中TNBS诱导的小鼠溃疡性结肠炎以辅助性T1（helper1,Th1）型炎症反应为主,OXZ诱导的小鼠溃疡性结肠炎以辅助性T2（helper2,Th2）型炎症反应为主。     

Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

The histopathological features and the associated clinical findings of ulcerative colitis (UC) are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite (SA) benefits rats with dextran sulfate sodium (DSS)-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA (10 mg/kg; intraperitoneally) was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7,14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased ir the order of Cycles 1,2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.     

Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB

This study investigated the alleviating effects of hydrogen sulfide (H₂S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 µmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H₂S. It was also found that H₂S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H₂S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway.     

腹腔注射丁酸盐对大鼠乙酸性结肠炎的预防作用(英文)

目的:探索腹腔注射丁酸盐对防止乙酸性结肠炎的疗效。创新点:首次对大鼠进行腹腔注射丁酸盐,通过与直肠灌注和口服比较,探索三种不同给药方式对预防乙酸性结肠炎的疗效差异。方法:以40只Wistar大鼠为实验对象,分组进行连续7天的腹腔注射、直肠灌注和口服100 mg/kg丁酸钠(SB),第8天进行乙酸(AA)直肠灌注,48小时后处死。记录实验大鼠的临床症状,包括体重减少、腹泻、便血等。对结肠切片进行组织病理学观察,最后对试验数据进行统计分析。结论:腹腔注射、直肠灌注和口服丁酸盐均能明显缓解大鼠乙酸性结肠炎的炎症,其中以腹腔注射疗效最佳。     

中药复方对戊四氮致痫大鼠海马神经元caspase-3表达的影响

目的：观察戊四氮（PTZ）致痫大鼠海马神经元caspase-3表达以及中药复方AAP的脑保护作用.方法：144只健康成年雄性Wistar大鼠随机分为对照组（CK组）、模型组（PTZ组）、中药大剂量组（AAPl组）、中药中剂量组（AAPm组）、中药小剂量组（AAPs组）和丙戊酸钠组（VPA组）;每组各6只.CK组和PTZ组分别给予生理盐水（4mL/kg.d）灌胃;中药各组分别给予中药复方大、中、小剂量（10.26g/kg、5.13g/kg、2.56g/kg）灌胃,每天1次;VPA组腹腔注射VPA（20mg/kg.d）.造模第一天,除CK组外,其余各组大鼠均腹腔注射戊四氮（PTZ）75mg/kg,观察记录大鼠行为学变化;于致痫后12h、2d、5d、7d相应时间点取材,制备脑标本;免疫组化检测caspase-3表达.结果：致痫后,除CK组外,其余各组海马区caspase-3阳性表达增强;7天,与PTZ组相比,AAPl组、AAPm组和AAPs组海马CA3区caspase-3阳性表达减弱（P〈0.05）.结论：caspase-3参与致痫大鼠海马神经元凋亡过程;AAP能降低caspase-3表达,减少神经元凋亡,有神经保护作用.     

诱发溃疡性结肠炎动物模型化学方法及评价

溃疡性结肠炎（ulcerative colitis,UC）又称慢性非特异性溃疡性结肠炎,流行病学资料提示溃疡性结肠炎的发病率在国内外都有逐年增高的趋势,溃疡性结肠炎的研究越来越受到国际肠病学家的关注,所以建立接近于人类的稳定的溃疡性结肠炎动物模型尤为重要。本文综述了近几年常用的诱发溃疡性结肠炎动物模型的化学方法及评价,以期为基础与临床研究应用提供参考。     

AMINO ACIDS' PROTECTIVE EFFECTS ON EXPERIMENTAL ACUTE RENAL FAILURE

ＩＮＴＲＯＤＵＣＴＩＯＮＡｃｕｔｅｒｅｎａｌｆａｉｌｕｒｅ(ＡＲＦ),ｕｓｕａｌｌｙｒｅｆｅｒｒｅｄｔｏａｓａｃｕｔｅｔｕｂｕｌａｒｎｅｃｒｏｓｉｓ,ｉｓａｃｏｍｍｏｎｓｙｎｄｒｏｍｅｃｈａｒａｃｔｅｒｉｚｅｄｂｙａｎａｂｒｕｐｔａｎｄｓｕｓｔａｉｎｅｄｄｅｃｌｉｎｅｉｎｇｌｏｍｅｒｕｌａｒｆｉｌｔｒａｔｉｏｎｗｉｔｈｒｅｓｕｌｔａｎｔａｚｏｔｅｍｉａ,ｃａｕｓｅｄｂｙａｃｕｔｅｉｓｃｈｅｍｉｃａｎｄ/ｏｒｔｏｘｉｃｉｎｊｕｒｉｅｓ.Ｉｔｉｓｎｏｔｉｍｍｅｄｉａｔｅｌｙｒｅｖｅｒｓｉｂｌｅｗｈｅｎｃａ…     

天麻素对模型大鼠海马Caspase-3表达的影响

目的：观察天麻素对癫痫大鼠海马Caspase-3表达的影响及其脑保护作用。方法：120只健康成年雄性Wistar大鼠随机分为对照组、PTZ（戊四氮）组、VPA（丙戊酸钠）组、Gb（天麻素大剂量）组和Gs（天麻素小剂量）组（n=24）。对照组和PTZ组分别以生理盐水（4mL/kg·d）灌胃;VPA组给予丙戊酸20mg．kg^-1,Gb组和Gs组分别给予天麻素200mg．kg^-1和100mg．kg^-1;每天1次,连续7天。造模第一天,除对照组大鼠外,余者均腹腔注射戊四氮75mg／kg,记录动物行为学变化。于致痫后12h、2d、5d和7d相应时间点取材,制备脑标本,免疫细胞化学术检测caspase-3表达。结果：致痫后12h,P11Z组Caspase-3有微量表达,其余各组几乎无表达;2—7d。PTZ组Caspase-3表达增加。与PTZ组比较,Gb组、Gs组及VPA组Caspase-3阳性表达降低,差异显著（P〈0．05）;与VPA组比较,Gb组和Gs组Caspase-3表达无显著差异（P〉0．05）。结论：天麻素能降低致痫大鼠海马神经元Caspase-3表达;可能通过抑制神经元凋亡发挥脑保护作用。     

AMINO ACIDS' PROTECTIVE EFFECTS ON EXPERIMENTAL ACUTE RENAL FAILURE

This study was carried out to elucidate the nephroprotective effects from a mixture of 8 L-amino acids and the possible mechanism of protection by this amino acid mixture. Acute renal failure model was induced by an intravenous administration of 10 mg/kg cisplatin to male Sprague-Dawley rats. A mixture of 8 L-amino acids or 0.9% saline was infused at a rate of 2 ml/h for 3 h, starting with a 2 ml bolus injection before cisplatin administration. Amino acids showed no acute effect on renal morphology. The infusion of a mixture of 8 L-amino acids increased GFR by 85% in control rats. The abnormalities of urine sodium and potassium excretion caused by cisplatin were markedly attenuated by the administration of the amino acid mixture. With the infusion of this amino acid mixture, cisplatin-induced abnormal state 4 respiration returned to control levels and the depressed state 3 respiration, respiratory control ratio and carbonyl cyanide p-trifluoromethoxyphenyl hydrazone-uncoupled respiration were ameliorated remarkably. A mixture of 8 L-amino acids showed marked nephroprotection against cisplatin-induced acute renal failure in rats and might function through augmentation of the cisplatin-injured renal mitochondrial electron transport-oxidative phosphorylation sequence, probably via stabilizing the membrane (including inner mitochondrial membrane) protein tertiary structure. In addition, this amino acid mixture remarkably increased GFR and decreased urine sodium excretion in rats.     

黎蒿叶叶绿素的提取及叶绿素铜钠盐的制备

研究了从黎蒿叶中提取叶绿素及制备叶绿素铜钠盐的最佳条件,结果表明黎蒿叶叶绿素提取的最佳条件为:乙醇浓度85%;料液比1:8;提取温度为80℃;浸提时间为4h;叶绿素铜钠盐制备条件为:皂化pH为11-12,65℃皂化30 min,酸化pH为2-3,65℃酸化20min;15%硫酸铜,铜代1h。     

MITOCHONDRIAL DYSFUNCTION AT THE EARLY STAGE OF CISPLATIN-INDUCED ACUTE RENAL FAILURE IN RATS

ＩＮＴＲＯＤＵＣＴＩＯＮＣｉｓ ｄｉａｍｍｉｎｅｄｉｃｈｌｏｒｏｐｌａｔｉｎｕｍ (Ⅱ ) (Ｃｉｓ ｐｌａｔｉｎ)ｉｓａｗｉｄｅｌｙｕｓｅｄａｎｔｉｎｅｏｐｌａｓｔｉｃａｇｅｎｔｔｈａｔｈａｓｎｅｐｈｒｏｔｏｘｉｃｉｔｙａｓａｍａｊｏｒｄｏｓｅ ｌｉｍｉｔｉｎｇｓｉｄｅｅｆｆｅｃｔ.Ｔｈｅｍｏｓｔｃｏｍｍｏｎｆｏｒｍｏｆｃｉｓｐｌａｔｉｎ ｉｎ ｄｕｃｅｄｒｅｎａｌｔｏｘｉｃｉｔｙｉｓｎｏｎ ｏｌｉｇｕｒｉｃａｃｕｔｅｒｅｎａｌｆａｉｌｕｒｅ.Ｔｈｅｕｎｄｅｒｌｙｉｎｇｍｅｃｈａｎｉｓｍｏｆｔｈｉｓｒｅｎａ…     

链脲佐菌素致大鼠糖尿病模型的实验研究

目的：探讨链脲佐菌素诱导速发型SD大鼠实验性糖尿病模型的建立。方法：采用一次性向大鼠腹腔内注射链脲佐菌素的方法，实验中监测血糖，并取胰腺组织用组织化学和免疫组织化学染色，以Motic Med 6．0显微图像分析系统分析糖尿病大鼠胰岛细胞的数量改变。结果：注射48h后大鼠血糖明显升高，并出现糖尿病表现。形态学观察到胰岛萎缩，B细胞数量明显减少（P〈0．01），灰度降低。结论：一次性足量给予SD大鼠链脲佐菌素，可成功复制出速发型糖尿病动物模型，此药物导致糖尿病的机制是损伤B细胞。此建模方法简单，费用低，血糖反应敏感，为糖尿病组织病理研究及相关实验提供了一个较好模型。     

大鼠慢性萎缩性胃炎模型的建立

目的 :建立稳定、价廉、实用的慢性萎缩性胃炎动物模型。方法 :采用 2 %水杨酸钠和30 %酒精混合溶液灌胃 ,并结合劳累、饥饱失常等多因素方法刺激Wistar大鼠胃粘膜 8周。结果 :CAG模型组大鼠较正常对照组大鼠体重明显减轻、胃粘膜腺体萎缩、炎细胞浸润 ,壁细胞数量减少且部分呈空泡样变性 ,停止作用 4周后仍无恢复。结论 :多因素联合作用 8周能建立良好的大鼠慢性萎缩性胃炎模型 ,且稳定性好。     

Conditioned taste aversion in Philippine rice rats (R. r. mindanensis): Comparisons among drugs,dosages, modes of administration,and sexes

The effects of select drugs, dosages, and modes of administration upon learned taste aversions were compared among groups of wild-caught male and female Philippine rice rats (R. r. mindanensis). Experiment 1 compared two-choice saccharin aversions for 28 days among groups intubated with copper sulfate, cyclophosphamide, lithium chloride, red squill, sodium chloride (control), or deionized water (control). Main results were that 375 mg/kg lithium chloride produced the greatest sustained aversions, whereas 198 mg/kg cyclophosphamide and 210 mg/kg red squill produced moderate aversions, with males showing more resistance to extinction than females. Experiment 2 compared saccharin aversion among matched groups of male and female rats that received low (36 mg/kg), moderate (105 mg/kg), or high (368 mg/kg) dosages of lithium by gavage, ip injection, or ingestion. Sex differences in rates of extinction were found for the ingestion and injection-dosed rats, but no sex difference was again found for rats dosed by gavage. A significant mode × day interaction indicated that extinction progressed more rapidly for rats dosed by gavage. For all modes of administration, high dosages yielded intense 28-day aversion, moderate dosages produced intermediate 3–5 day aversion, and low dosages caused no aversion.     

野鸦椿果实水提物对急性酒精性肝损伤的保护作用

40只雄性SD大鼠随机分成5组,分别是正常组、模型组和野鸦椿高、中、低剂量,采用50%乙醇灌胃造模,同时给相应剂量野鸦椿水提物,给药一周后检测大鼠血清AST、ALT、TBIL、DBIL以及TG含量,并取肝组织HE染色进行病理学检.通过以上处理后,野鸦椿水提物各剂量组大鼠血清AST、ALT、TBIL、DBIL及TG均不同程度的下降,病理组织学检查给药组肝组织病理损害也较模型组轻;以上结果说明野鸦椿水提物对大鼠急性酒精性肝损伤具有保护作用.     

Benzodiazepine administration prevents the use of error-correction mechanisms during fear extinction

Three experiments examined the effect of systemic administration of the benzodiazepine midazolam on extinction and re-extinction of conditioned fear. Experiment 1 demonstrated that midazolam administration prior to extinction of a conditioned stimulus (CS) impaired that extinction when rats were subsequently tested drug free; however, extinction was spared if rats were extinguished, reconditioned, and re-extinguished under midazolam. Experiment 2 provided a replication of this effect within-subjects; rats were conditioned to two CSs (A and B), extinguished to one (A-), reconditioned to both, and then extinguished/re-extinguished to both stimuli in compound (AB-), under either vehicle or midazolam. On the drug-free test, rats given midazolam froze more to the CS that had been extinguished (B) than the one that been re-extinguished (A). The final experiment examined whether extinction under midazolam was regulated by prediction error. Rats were trained with three CSs (A, B, C) and extinguished to two (A-, C-). These stimuli then underwent additional extinction under midazolam or vehicle, with one CS now presented in compound with the non-extinguished CS (AB-, C-). Rats were then tested for fear of A relative to C. Rats given vehicle showed a deepening of extinction to A relative to C, as is predicted from error-correction models; however, rats given midazolam failed to show any such discrepancy in responding. The results are interpreted to indicate that the drug reduced prediction error during extinction by reducing fear, and rats were able to re-extinguish fear via a retrieval mechanism that is independent of prediction error.     

Interstimulus interval determines whether ethanol produces conditioned place preference or aversion in mice

DBA/2J mice were exposed to a distinctive floor stimulus (CS+) and ethanol (2 g/kg) in a place conditioning paradigm. A different floor stimulus (CS?) was presented with saline. Mice injected just before or 30 min before CS exposure (Groups 0, ?30) showed conditioned place preference, whereas mice injected right after exposure to the CS (Group 5) displayed place aversion (Experiment 1). None of the other groups (?120, ?60, 15, 60) showed place conditioning. Handling and saline injection given just before or after CS exposure were unable to produce place conditioning (Experiment 2). However, there was a positive relationship between ethanol concentration (10% vs. 20%) and test performance, suggesting that peritoneal irritation influences place conditioning (Experiment 3). Overall, these findings support the suggestion that intraperitoneal injection of ethanol produces an initial short-duration aversive effect that is followed by a longer lasting positive motivational effect.     

大气压冷等离子体提高乙醇转化率的实验参数优化研究

以酿酒酵母(Saccharomyces cerevisiae)为研究对象,研究大气压冷等离子体激活酿酒酵母提高乙醇转化率的工艺条件。在单因素实验基础上,选取等离子体处理时间、等离子体电源电压和处理菌液体积为影响因子,以乙醇转化率为响应值,应用Box-Behnken中心组合实验建立数学模型,进行响应面分析。结果表明,大气压冷等离子体提高乙醇转化率的最佳实验参数为:处理时间1 min,电源电压24 V,处理菌液体积9 mL。在此条件下,乙醇转化率达到0.58 g/g,比未处理过的酿酒酵母发酵葡萄糖生成乙醇的转化率高23.6%。     

硫酸氢钠催化合成丁酸戊酯

以正丁酸和戊醇为原料，硫酸氢钠为催化剂合成了丁酸戊酯．最佳合成条件：以0．1mol正丁酸为基准，醇酸摩尔比为1．2：1，催化剂用量0．2克，甲苯5毫升，反应时间30min，丁酸的酯化率可达99．3％，在无甲苯存在下，合成食品级丁酸戊酯，酯化率可达99．7％．