熊果酸对顺铂所致小鼠耳毒性的防护作用研究

目的研究熊果酸对顺铂所致小鼠耳毒性的防护作用。方法 40只健康成年BALB/c小鼠随机分成对照组(腹腔注射等量生理盐水)、顺铂组(腹腔注射顺铂4.5 mg/kg)、顺铂+熊果酸组(一侧腹腔注射顺铂4.5 mg/kg,同时对侧腹腔注射熊果酸80 mg/kg)和熊果酸组(腹腔注射熊果酸80 mg/kg),每组10只。各组动物均连续注射5 d,每天1次。应用听脑干反应(auditory brainstem response,ABR)测试,观察用药前后小鼠听功能的改变;并采用异硫氰酸四甲基罗丹明(tetramethylrhodamine isothiocyanate,TRITC)标记的鬼笔环肽荧光染色方法,观察小鼠耳蜗毛细胞的形态变化。结果顺铂组小鼠ABR阈移较对照组明显增大(P<0.05),并且耳蜗毛细胞破坏严重;而给予熊果酸可有效降低顺铂对小鼠耳蜗的破坏(P<0.05)。结论熊果酸可有效防护顺铂的耳毒性,改善听功能。     

阿司匹林对顺铂损伤豚鼠耳蜗螺旋神经节HO-1表达的影响

目的:研究阿司匹林(acetylsalicylic acid,ASA)对顺铂(cisplatin,DDP)损伤豚鼠耳蜗螺旋神经节(spiral ganglion,SGNs)细胞中血红素加氧酶-1(heme oxygenase-1,HO-1)表达的影响,并探讨ASA通过诱导HO-1的表达对DDP损伤豚鼠耳蜗螺旋神经节的保护作用。方法:将40只豚鼠随机分成4组,每组10只。A组(正常对照组):每日以0.9%生理盐水10 mL/kg腹腔注射;B组(DDP组):每日腹腔注射顺铂10 mg/kg;C组(ASA+DDP组):每日腹腔注射阿司匹林100 mg/kg预处理1 h,再腹腔注射顺铂10 mg/kg;D组[HO-1抑制剂锌原卟啉IX(ZnppIX)+ASA+DDP组]:先同时予以ZnppIX 10μmol/kg+阿司匹林100 mg/kg腹腔注射预处理1 h,再予以顺铂10 mg/kg腹腔注射。每组均早晚各一次,持续用药3 d后,观察各组豚鼠ABR阈值变化,并采用免疫组织学、免疫荧光学、蛋白免疫印迹检测各组间耳蜗螺旋神经节细胞中HO-1的表达情况。结果:在各组豚鼠的检测结果中,D组ABR阈值...     

顺铂致豚鼠耳毒性作用中细胞凋亡及caspase-3表达的研究

目的：通过顺铂（CDDP）致豚鼠耳毒性作用中细胞凋亡及caspase-3表达的观察,探讨CDDP致耳毒性的作用机制。方法：实验组和对照组豚鼠各10只,前者以CDDP 2.0 mg/（kg.d）连续腹腔注射6 d,后者以等量生理盐水替代。通过ABR测试用药前后豚鼠听力的变化,应用TUNEL法检测耳蜗凋亡细胞,免疫组化法检测caspase-3在耳蜗中的表达。结果：实验组耳蜗凋亡细胞明显增多,caspase-3的表达亦明显增强。结论：caspase-3介导的信号传导机制,可能参与了CDDP所致的耳蜗细胞凋亡过程,导致耳毒性的发生。     

顺铂体内注射对子代豚鼠耳蜗毛细胞的影响

[目的]了解孕晚期顺铂暴露是否会诱导子代豚鼠耳蜗毛细胞损伤.[方法]将孕晚期豚鼠12只随机分为两组,在孕50 d至56 d,顺铂组经腹膜腔注射顺铂1,5mg/kg·d,对照组注射生理盐水1.5 mg/kg·d.出生后14d,应用原位末端转移酶标记技术(TUNEL)和Caspase-3免疫组化染色检测毛细胞凋亡情况.[结...     

豚鼠耳蜗外毛细胞凋亡时听力变化的实验观察

目的观察耳蜗外毛细胞发生凋亡时听力改变情况.方法对20只豚鼠药物造模,诱发耳蜗外毛细胞发凋亡.应用TUNEL技术观察凋亡表达,测试ABR阈值观察听力变化.结果应用丁胺卡那霉素1天即可诱发豚鼠耳蜗外毛细胞发生凋亡,连续应用3d,耳蜗外毛细胞凋亡呈强阳性表达,但ABR阈值无明显改变;随着用药时间延长,凋亡细胞数目增加,甚至出现部分毛细胞缺失现黎,此时ABR阈值明显升高.结论耳蜗外毛细胞发生凋亡早期对豚鼠听力无明显影响,随着耳毒性药物应用时间延长,豚鼠ABR阈值升高可能存在两种原因毛细胞凋亡或毛细胞坏死.     

脑神经生长素防护顺铂致耳蜗螺旋神经节损伤的研究

目的探讨脑神经生长素 (cerebralnervegrowthfactor,CNG)作为防护药物拮抗顺铂致耳蜗螺旋神经节毒性作用。方法选 2 4只豚鼠 ,随机分为 3组 ,每组 8只。顺铂组连续 5d腹腔注射顺铂 2mg/(kg·d) ;CNG组在给予顺铂前 2d开始大腿内侧肌肉注射CNG 2mg/(kg·d) ;正常对照组连续 5d腹腔注射生理盐水 2mg/(kg·d) ;用药前后测试听性脑干反应 (auditorybrainstemresponse ,ABR)阈值 ,处死动物制作耳蜗标本 ,应用透射电镜观察并用免疫组化法测定诱导型一氧化氮合酶 (inducednitricoxidesynthase ,iNOS)的表达。结果顺铂组动物ABR听阈值显著升高 ,透射电镜下见螺旋神经节细胞的细胞器损伤严重 ,iNOS阳性染色 ,呈棕黄色。CNG组动物ABR阈值略有升高 ,但较顺铂组为低 (P <0 .0 1)。螺旋神经节细胞的细胞器损伤较轻 ,iNOS显色浅 ,呈浅黄色。结论CNG可减少耳蜗iNOS表达 ,保护耳蜗螺旋神经节 ,从而保护听力     

顺铂对豚鼠耳蜗毛细胞损害的形态及机理研究

目的：观察顺铂对豚鼠耳蜗毛细胞的损害，并阐述一氧化氮（nitric oxide,NO）在其耳毒性机制中的作用。方法：将20只豚鼠随机分成两组，试验组腹腔注射顺铂0．5ml，对照组给予同等量的生理盐水，5天后做听性脑干反应（auditory brainstem respones,ABR)测听，此后处死动物，取出耳蜗，应用免疫组化技术、光镜及扫描电镜观察耳蜗毛细胞的损害。结果：试验组动物测试ABR听阈明显提高，光镜下见耳蜗毛细胞明显变性，诱导型一氧化氮合酶阳性染色，电镜下见毛细胞的纤毛散乱、倒伏甚至散失。结论：顺铂对豚鼠耳蜗毛细胞有明显的损害作用，而O在其耳毒性机制中发挥着重要的作用。     

豚鼠耳蜗外毛细胞凋亡时听力变化的实验研究

目的：观察耳蜗外毛细胞发生凋亡时听力改变情况。方法：对20只豚鼠药物造模,诱发耳蜗外毛细胞发生凋亡。应用TUNEL技术观察凋亡表达,测试ABR阈值观察听力变化。结果：应用丁胺卡那霉素1天即可诱发豚鼠耳蜗外毛细胞发生凋亡,连续应用3d,耳蜗外毛细胞凋亡呈强阳性表达,但ABR阈值无明显改变;随着用药时间延长,凋亡细胞数目增加,甚至出现部分毛细胞缺失现象,此时ABR阈值明显升高。结论：耳蜗外毛细胞发生凋亡早期对豚鼠听力无明显影响,随着耳毒性药物应用时间延长,豚鼠ABR阈值升高可能存在两种原因：毛细胞凋亡或毛细胞坏死。     

蛋氨酸对化疗药物引起内耳损伤的保护作用

目的 研究蛋氨酸对化疗药物顺铂导致耳毒性的保护作用.方法 将30只昆明小鼠随机分为3组.顺铂组(n=10):给予顺铂3.5mg·kg-1·d-1腹腔注射,连续7d;蛋氨酸+顺铂组(n=10):蛋氨酸300mg·kg-1·d-1腹腔注射,30min后给予顺铂3.5mg·kg-1·d-1腹腔注射,连续7d;对照组(n=10):生理盐水3.5mg·kg-1·d-1腹腔注射,连续7d.实验第8天,利用听觉脑干诱发电位(auditory brainstem response,ABR)对3组小鼠进行听功能测试,然后迅速断头取出双侧内耳,解剖耳蜗基底膜,铺片并HE染色,普通光学显微镜下观察.结果 在ABR测试中,对照组小鼠实验前后听力无明显变化;顺铂组小鼠听阈及Ⅰ波和Ⅲ波潜伏期与对照组相比变化明显;蛋氨酸+顺铂组小鼠听阈及Ⅰ波和Ⅲ波潜伏期与对照组相比也出现变化,但变化程度较顺铂组明显减轻.光镜观察:对照组动物耳蜗基底膜外毛细胞排列整齐;顺铂组基底膜外毛细胞有不同程度的坏死、脱落,尤以底转缺失严重;蛋氨酸+顺铂组耳蜗毛细胞损伤较顺铂组明显减轻.结论 化疗药物顺铂对耳蜗毛细胞引起损害,而蛋氨酸对这种损害有较好的保护作用.     

水杨酸钠对顺铂所致听性损害的拮抗作用研究

目的 观察水杨酸钠(NaSA)对抗顺铂(CDDP)耳毒性的作用.方法 选用健康、耳廓反射灵敏的白毛赤目豚鼠30只,随机分为两组:①CDDP+NaSA(100mg/kg)组和②cDDP+Ns(对照组).采用ABR、超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及光镜技术,观察用药前后各指标的变化.结果 ①组的ABR阈值明显小于对照组(P<0.01).①组血清和耳蜗组织中MDA含量较对照组明显降低(P<0.05,P<0.01),SOD活性较对照组明显升高(P<0.01).耳蜗光镜标本显示,对照组外毛细胞受损程度较重,①组比对照组外毛细胞受损程度明显为轻.结论 水杨酸钠对顺铂所致的耳毒性具有明显拮抗作用.     

黄芩苷与橙皮苷对顺铂所致小鼠肝损伤的保护作用比较

目的:研究黄芩苷与橙皮苷对顺铂所致小鼠肝损伤的保护作用,并比较二者的作用。方法:将ICR小鼠分为4组,即正常组、顺铂模型组、黄芩苷组和橙皮苷组,给药组分别给予黄芩苷(300mg/kg)和橙皮苷(300mg/kg),连续灌胃7天,正常组和模型组给予同体积溶剂,在第3天给药后1h时腹腔注射顺铂(5mg/kg)连续5天,末次注射15h后断头处死小鼠,取肝脏和血液进行检测,通过肝脏的病理组织学检测、谷丙转氨酶(ALT)、谷草转氨酶(AST)测定可反映顺铂引起肝脏损伤,利用生化法测定肝组织丙二醛(MDA)、超氧化物岐化酶(SOD)和谷胱甘肽(GSH)可反映其氧化损伤情况。结果:黄芩苷和橙皮苷可显著抑制顺铂引起小鼠血清ALT和AST水平升高,减少MDA的形成,恢复抗氧化酶SOD的活性,并抑制GSH的耗竭,但黄芩苷的作用比橙皮苷更显著。此外,黄芩苷和橙皮苷明显减轻肝脏水样空泡样变性、炎症浸润和坏死。结论:黄芩苷与橙皮苷均对顺铂所致小鼠肝损伤均具有明显保护作用,尤其是黄芩苷,其保护作用主要与抗氧化作用密切相关。     

缝隙连接蛋白在老年大鼠认知功能障碍中作用

目的:探讨老年大鼠认知功能障碍和海马神经元电突触缝隙连接蛋白CX36之间的关系.方法:SD老年雄性大鼠40只,随机分为4组(n=10).对照组(C组):灌胃2 ml生理盐水21d后行腹腔注射生理盐水2 ml,连续3 d;氯胺酮组(K组):灌胃2 ml生理盐水21 d后行腹腔注射氯胺酮80 mg/(kg·d),连续3d;盐酸多奈哌齐Ⅰ组(D1组):灌胃盐酸多奈哌齐1 mg/(kg·d)持续21d后行腹腔注射氯胺酮80 mg/(kg·d),连续3d;盐酸多奈哌齐2组(D2组):灌胃盐酸多奈哌齐3 mg/(kg·d)持续21d后行腹腔注射氯胺酮80mg/(kg·d),连续3d.停药1d后进行Morris水迷宫行为学测试.测试完毕后立即处死大鼠,制备海马脑片进行免疫组织化学染色,测定海马CX36蛋白的表达;RT-PCR方法检测CX36 mRNA表达;ELISA测定各组海马乙酰胆碱浓度.结果:①水迷宫测试结果K组第2,3天的潜伏期和游泳距离均明显长于C组(P＜0.05),盐酸多奈哌齐组(D1,D2组)第3天的潜伏期和游泳距离明显缩短于K组(P＜0.05),D1与D2之间差异无统计学意义.②CX36蛋白的表达K组大鼠海马CX36蛋白表达显著减少,与C组、D1组和D2组比较差异有统计学意义(P＜0.05),而D1组、D2组与C组比较差异无统计学意义,D1组与D2组比较差异也无统计学意义.③各组海马CX36 mRNA的差异无统计学意义.④海马乙酰胆碱浓度与C、K组比较,D1、D2组大鼠乙酰胆碱浓度明显增高,差异具有统计学意义(P＜0.05).结论:缝隙连接蛋白CX36在老年大鼠认知功能障碍中起重要作用,其功能可能主要通过快速调节发挥作用.     

Effects of Matricaria chamomilla extract on motor coordination impairment induced by scopolamine in rats

Objective: To evaluate the effect of ethanolic extract of chamomile on balance and motor learning in rats receiving scopolamine and intact rats.Methods: Fourty-two rats were divided into 6 groups(n = 7). Control group received distilled water. Rats in Group 2 were given 1 mg/kg scopolamine. Groups 3 and 4received chamomile extract 200 mg/kg and 500 mg/kg, respectively, and scopolamine simultaneously for 20 days. Intact groups(Groups 5 and 6) only received chamomile extract 200 mg/kg and 500 mg/kg, respectively. Motor coordination of rats was assessed with rotarod apparatus.Results: According to the obtained results, compared with the control group, scopolamine significantly decreased time spent on rotarod performance(P 0.001). Compared with scopolamine group, the strength and staying on rotarod apparatus in Group 3significantly increased(P 0.05). The results of this research showed that intact groups that received only chamomile extract at doses of 200 mg/kg and 500 mg/kg significantly increased time spent on rotarod, compared with scopolamine group(P 0.001).Conclusions: The results of this study indicated the high antioxidant property and protective effect of chamomile extract on motor coordination in the groups that received scopolamine.     

Liver enzymes derangement and the influence of diet in animals given oral albendazole

Background:

Albendazole is used as an anthelmintic in the treatment of some parasitic infections. This study determined how the effects of albendazole on liver enzymes are influenced by diet.

Materials and Method:

Thirty adult male Wistar rats of mean weight 304.12 ± 11.34 g were randomly grouped into five: Group A: Control, was given rat pellets and water only; Group B received 15 mg/kg/d of albendazole while fasting; Group C received 15 mg/kg/d of albendazole with fatty meal; Group D received 15 mg/kg/d of albendazole with normal diet (rat pellets); and, Group E received 30 mg/kg/d of albendazole with normal diet (rat pellets); they were given orally for 3 consecutive days. The animals were sacrificed thereafter and blood samples obtained for quantitative study of the serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP).

Results:

Significant elevation in the serum levels of the transaminases especially in animals which were on their normal diet (rat pellets), while ALP was either reduced or increased based on dietary factors.

Conclusions:

Oral administration of albendazole before meal or with a fatty diet could help limit severe elevation of liver enzymes associated with its use, while still ensuring optimal efficacy.     

Prophylactic effects of Salvia miltiorrhizae and ligustrazine on experimental respiratory distress syndrome induced by oleic acid in rats

The prophylactic effects of Salvia miltiorrhizae and ligustrazine on experimental respiratory distress syndrome (RDS) in Wistar rats were observed and compared with the dexamethasone. Sixty-two male rats weighing 194.68 +/- 20.40 g (M +/- SD) were used in this experiment. The rats were randomly divided into five (A-E) groups. Group A was given normal saline 0.1 ml/kg alone and group B oleic acid 0.1 ml/kg; both were injected in tail vein, and the latter produced typical RDS. Group C, D, E were injected intraperitoneally with agents of dexamethasone 2 mg/kg, Salvia miltiorrhizae 1.5 g/kg, and ligustrazine 20mg/kg, respectively, 15 minutes before oleic acid intravenous injection. All of the animals were sacrificed quickly 6 hours after injections and lung tissues were taken and examined with light and electronic microscope. The results showed that all of these medicines could minimize the lesions caused by oleic acid. Lung/body index was reduced. Prophylactic effects of Salvia miltiorrhizae and ligustrazine were similar to dexamethasone. The authors considered that preventive use of Salvia miltiorrhizae or ligustrazine could protect the lung from the development of RDS.     

Potentiation of inner ear damage following electron beam irradiation with CDDP administration

This study was designed to examine the combined ototoxic effects of cisplatin, an antitumor platinum compound, administration and electron beam irradiation on the inner ear of guinea pigs, histopathologically. One group received saline solution 4 ml/kg/day and the other group received cisplatin of 2 mg/4 ml/kg/day for five consecutive days. The right temporal bones of all animals of both groups were exposed to the electron beam of 14 Gy/day 3 hours after the daily injection of saline or cisplatin. All animals were sacrificed for inner ear histopathological findings 21 days after the last injection. A combination of cisplatin administration and electron beam irradiation produced a severe potentiation of the outer hair cell damage with no inner hair cell damage. Therefore, in treatment of head and neck carcinomas, it is important to pay attention to inner ear damage caused by combination therapy of cisplatin and electron beam irradiation which involves the inner ear.     

培美曲塞与多西他赛联合顺铂治疗晚期非小细胞肺癌的疗效比较

目的:比较培美曲塞与多西他赛联合顺铂治疗晚期非小细胞肺癌的临床疗效及不良反应.方法:将符合入组标准的40例晚期非小细胞肺癌患者随机分成2组:观察组以培美曲塞联合顺铂化疗21例,培美曲塞500mg/m2静脉滴注第1天,顺铂80 mg/m2静脉滴注第1～3天,从化疗前一周开始直至治疗结束;对照组19例:多西他赛175 mg...     

咪达唑仑对顺铂诱发猫呕吐的预防作用

目的 探讨咪达唑仑预防顺铂诱发猫恶心、呕吐的效果.方法 健康杂种家猫18只,随机分为3组：单纯模型组（顺铂组,C组）、格拉斯琼组（G组）和咪达唑仑组（M组）,每组6只,分别静注生理盐水3ml、格拉斯琼0.15mg/kg和咪达唑仑0.50mg/kg,20min后顺铂3mg/kg腹腔注射.观察动物镇静程度和10h内恶心、呕吐情况.结果 顺铂能诱发猫产生严重的恶心、呕吐反应;G组和M组猫干呕潜伏期延长,恶心、呕吐次数减少（P＜0.01）.结论 猫静脉注射咪达唑仑0.5 mg/kg能预防顺铂诱发的恶心、呕吐.     

复方葛根注射液对血液流变学及血小板聚集功能的影响

目的观察复方葛根注射液对大鼠血小板聚集功能及兔血液流变学的影响.方法 SD大鼠50只,随机分为正常组、试药组(20、40、80 mg/kg)及阳性药(川芎嗪40 mg/kg)组,测定给药3 d后血小板聚集率;家兔30只,随机分为正常组、试药组(10、20、40 mg/kg)及阳性药(川芎嗪20 mg/kg)组,测定给药3 d后血液流变学指标.结果复方葛根注射液能显著抑制血小板的聚集率;显著降低全血黏度、血浆黏度、红细胞压积及纤维蛋白原.结论复方葛根注射液对血液流变学有改善作用.     

激素性股骨头坏死动物模型的诱导及观察

目的：通过马血清、激素联合作用于实验家兔，制备典型骨坏死动物模型，进一步探究激素性股骨头坏死的发病机理。方法：选新西兰白兔60只，随机分成4组。A组：20只，经静脉2次单纯注射马血清每次10ml/kg，间隔3周；B组：15只，连续3日腹腔内注射甲基强的松龙每日45mg/kg；C组：20只，先静脉2次注射马血清每次10ml/kg，间隔2周。第2次注射马血清后2周，连续3日腹腔内注射甲基强的松龙每日45mg/kg；D组：5只，对照组。分别于最后1次给药后1、2、3、5、7周处死取材。标本常规组织病理学检查，并进行动脉墨汁灌注观察。结果：在马血清和激素协同作用的C组中，股骨头内小动脉损害严重，血栓形成广泛，轮骨下灌注血管数量减少明显，共有74％的标本发生骨坏死。结论：激素性股骨头坏死是一个复杂的病理生理过程，是由多因素共同作用的结果。