夏荔芪胶囊对良性前列腺增生模型大鼠PCNA、caspase-3表达水平的影响

目的:探讨夏荔芪胶囊对良性前列腺增生(BPH)模型大鼠增殖细胞核抗原(PCNA)、半胱氨酸蛋白酶3(caspase-3)表达水平的影响。方法:50只雄性SD大鼠,随机分为5组,每组10只:空白组(假手术组),模型组,夏荔芪高、低剂量治疗组[1.20 g/(kg·d)、0.61 g/(kg·d)]及非那雄胺治疗组[0.8 mg/(kg·d)]。采用去势后皮下注射丙酸睾酮[0.5 mg/(kg·d),30 d],建立大鼠BPH模型。空白组及模型组予以生理盐水,治疗组予以相应药物,造模成功后连续灌胃30 d。实验结束后将各组大鼠于麻醉下留取双侧前列腺组织后处死,计算大鼠前列腺指数(前列腺湿重/体重);免疫组化法检测大鼠前列腺组织中PCNA的表达情况;免疫荧光法检测大鼠前列腺组织中caspase-3的表达水平。结果:与空白组相比,模型组的前列腺湿重(g)及前列腺指数(mg/g)明显增加(1 326±60 vs 471±17;2.89±0.18 vs 1.06±0.06,P均0.01);与模型组比较,各治疗组的前列腺湿重及前列腺指数则明显降低,其中,夏荔芪高剂量组较低剂量组下降更明显(914±36 vs 1 099±46;2.02±0.08 vs 2.39±0.11,P均0.01),而各治疗组中以非那雄胺组(817±53 vs 471±17;1.83±0.10 vs 1.06±0.06,P均0.01)降低最明显。免疫组化结果显示,与空白组相比,模型组大鼠前列腺组织中PCNA表达明显增多,各治疗组与模型组相比,前列腺组织中PCNA表达均有明显减少,其中夏荔芪高剂量治疗组减少较为明显。免疫荧光结果显示,与空白组相比,模型组大鼠前列腺组织caspase-3表达量降低,各治疗组与模型组相比,前列腺组织中caspase-3表达明显增高,其中非那雄胺治疗组增高较为明显。结论:夏荔芪胶囊能明显降低BPH大鼠前列腺湿重及前列腺指数,通过降低前列腺组织中PCNA的表达水平,增高前列腺组织中caspase-3的表达,可能是其治疗BPH大鼠的机制。     

不同剂量芪药鸡金粥对氟尿嘧啶所致大鼠胃肠黏膜损伤的影响

目的比较不同剂量芪药鸡金粥对化疗后大鼠胃肠黏膜及其相关症状的保护作用。方法将40只大鼠随机分为模型组、高剂量药膳组、常规剂量药膳组、低剂量药膳组及空白组,各8只。于实验第1天行一次性腹腔注射氟尿嘧啶150mg复制化疗所致胃肠黏膜损伤大鼠模型。造模后,模型组和空白组行白粥10mL/kg灌胃,药膳组分别行芪药鸡金粥20mL/kg、10mL/kg、5mL/kg灌胃,1次/d,持续15d。于实验结束对大鼠胃黏膜、回肠黏膜病理结构改变进行评价。结果各组大鼠胃黏膜绒毛结构无明显差别,但充血程度各异。各组大鼠肠黏膜病理结构的形态存在不同,其病理损伤等级差异无统计学意义(P0.05);但总体上以模型组损伤最为严重,低剂量药膳组次之,高剂量药膳组黏膜损伤程度最轻。结论芪药鸡金粥对较长时间化疗后大鼠胃肠黏膜损伤的保护作用有待进一步探讨,不同剂量药膳组之间无明显量效关系,有待基于药理学角度进一步研究。     

雄蚕益肾方对雄性迟发性性腺功能减退大鼠睾丸组织生物钟基因表达的影响

目的:探讨雄蚕益肾方对雄性迟发性性腺功能减退症(LOH)大鼠睾丸组织细胞生物钟基因表达的影响。方法:48只8周龄雄性SD大鼠随机分为正常组，模型组，丙酸睾酮组，雄蚕益肾方低、中、高剂量组。模型组，丙酸睾酮组，雄蚕益肾方低、中、高剂量组大鼠腹腔注射480 mg/(kg·d)D-半乳糖(D-gal),连续注射56 d进行LOH造模，正常组大鼠每日腹腔注射相同体积生理盐水。造模成功后，雄蚕益肾方低、中、高剂量组分别给予10.4、20.8、41.6 g/(kg·d)体重剂量的雄蚕益肾方中药汤剂灌胃，每组每日均早、晚各灌胃1次；丙酸睾酮组大鼠肌注5.21 mg/(kg·d)体重剂量的丙酸睾酮，每周3次；正常组和模型组给予相同体积的蒸馏水灌胃；各组均连续操作28d。实验结束后，采血离心取上清液ELISA法检测睾酮(T)水平，取睾丸组织进行RT-qPCR、Western印迹分别检测BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1 mRNA表达量和蛋白表达水平。结果:模型组大鼠血清睾酮水平、睾丸组织BMAL1、NR1D1、PER2、CRY1、StAR、CYP11A1在mRNA表达量...     

生地黄汤对卵巢早衰大鼠骨代谢的干预作用

目的研究生地黄汤对卵巢早衰大鼠骨代谢的影响。方法 48只成年雌性SD大鼠,随机分为空白组、模型组、阳性对照组、生地黄汤高、中、低剂量治疗组。除空白组外,其余各组每日灌胃雷公藤多甙片75 mg/kg,连续造模14 d。从第15 d起,模型组灌胃生理盐水2 mL/kg;阳性对照组灌胃补佳乐1 mg/kg;高、中、低剂量治疗组灌胃生地黄汤(12、6、3 g/kg),每日1次,连续给药21天。放射免疫法测定血清中雌激素(E2)、孕酮(P)的含量;比色法检测血清中钙、磷的含量;ELISA法检测血清中碱性磷酸酶(ALP)、骨碱性磷酸酶(BALP)、1,25二羟基维生素D_3(1,25(OH)_2D_3)含量。结果与模型组比较,生地黄汤高、中剂量治疗组血清中E2、P水平升高(P0.05);生地黄汤高剂量组血清钙、磷的含量高于模型组(P0.05);生地黄汤各剂量组血清ALP、BALP含量均较模型组降低(P0.05),1,25(OH)2D3含量高于模型组(P0.01)。结论生地黄汤可以通过类雌激素样作用升高血清雌二醇水平,改善早衰卵巢功能,同时增强成骨细胞活性,使骨形成大于骨吸收,调节骨代谢平衡,改善卵巢功能减退引起骨质疏松。     

前列腺水丸对慢性细菌性前列腺炎大鼠血清IL-6和TNF-α水平的影响

目的:探讨前列腺水丸对慢性细菌性前列腺炎(CBP)大鼠血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平的影响。方法:健康成年雄性W istar大鼠50只,体重180~220 g,随机均分为5组:正常对照组、模型组、水丸高剂量组、水丸低剂量组、左氧氟沙星组。前列腺注射大肠埃希菌(107个/m l,0.2 m l/只),建立CBP大鼠动物模型。造模成功1个月后,用前列腺水丸高[32.4 g/(kg.d)]、低[16.2 g/(kg.d)]剂量灌胃治疗,阳性对照组用左氧氟沙星片[0.27 g/(kg.d)]灌胃,模型组和正常对照组用蒸馏水灌胃。连续治疗30 d后,应用放射免疫法检测感染的大鼠血清IL-6、TNF-α。结果:前列腺水丸高、低剂量组大鼠血清IL-6、TNF-α的水平明显低于模型组,与模型组比较差异显著P<0.01)。结论:前列腺水丸对大鼠CBP有一定治疗作用,其作用机制可能与降低血液中细胞因子IL-6、TNF-α水平有关。     

桂枝茯苓胶囊对前列腺增生模型大鼠的作用效果和机制研究

目的探讨桂枝茯苓胶囊对良性前列腺增生(BPH)模型大鼠的作用效果及可能存在的机制。方法将50只雄性SD大鼠,随机分为空白组(假手术组),前列腺增生模型组,非那雄胺组及桂枝茯苓胶囊高、低剂量组,共5组,每组10只。将SD大鼠去势后皮下注射丙酸睾酮,持续28d,建立大鼠前列腺增生模型。造模同时,空白组及模型组予以生理盐水,治疗组分别予以相应剂量的非那雄胺和桂枝茯苓胶囊,连续灌胃28 d。造模结束后,留取静脉血,将大鼠麻醉,取双侧前列腺组织后,处死大鼠。计算大鼠前列腺指数(前列腺湿重/体重),并对前列腺组织进行HE染色观察病理变化,通过Elisa检测大鼠血清和前列腺组织中的双氢睾酮(DHT)含量,通过qRT-PCR检测大鼠前列腺组织的VEGF和TGF-β1的m RNA表达含量。结果研究结果显示:与空白组相比,模型组的前列腺湿重(g)及前列腺指数(mg/g)明显增加(1009.31±56.97 vs 431.09±11.28;2.27±0.14 vs 1.00±0.03,P均0.01);与模型组比较,各治疗组的前列腺湿重及前列腺指数则明显降低,其中,桂枝茯苓胶囊高剂量组较低剂量组下降更明显(650.55±19.66 vs1009.31±56.97;1.49±0.05vs2.27±0.14,P均0.01)。Elisa检测显示,与空白组相比,模型组血清和前列腺组织中的DHT均升高,P均0.01,各治疗组与模型组比较,血清和前列腺组织中DHT均降低,其中非那雄胺组降低最明显,P均0.01。qRT-PCR结果显示,与空白组相比,模型组大鼠前列腺组织VEGF的表达水平升高,TGF-β1表达水平降低,各治疗组与模型组相比,前列腺组织中TGF-β1表达明显增高,而VEGF表达明显减少,其中桂枝茯苓胶囊高剂量组增高较为明显。结论研究发现桂枝茯苓胶囊能明显降低BPH模型大鼠前列腺湿重及前列腺指数,通过降低血清和前列腺组织的DHT以及降低前列腺组织中VEGF的表达水平,增高前列腺组织中TGF-β1的表达,可能是其治疗BPH的作用机制。     

基于 Caspase-3/Bcl-2/Bax信号通路探究加味旋覆代赭汤治疗食管癌前病变的作用机制

目的 探究加味旋覆代赭汤对食管癌前病变大鼠Caspase-3/Bcl-2/Bax信号通路的调控作用机制。方法:将48只雄性SD大鼠随机分为4组,空白组、模型组、中药组、西药组,每组各12只。除空白组外均采用复合造模法制作食管癌前病变大鼠模型,造模成功后,分别进行药物灌胃干预,空白组、模型组用生理盐水灌胃,中药组和西药组分别给予加味旋覆代赭汤、西药(雷贝拉唑+莫沙必利)灌胃,给药8周取材。利用光学显微镜观察食管上皮组织的形态学变化;分别应用蛋白质印迹法(Western-blot)及聚合酶链式反应(PCR)检测食管上皮组织Caspase-3、Bcl-2及Bax的表达水平。结果:与空白组比较,模型组大鼠食管上皮病理积分升高(P<0.01);与模型组比较,中药组、西药组大鼠食管上皮病理积分均降低(P<0.01)。PCR及Western-blot检测结果显示,与空白组比较,模型组大鼠Caspase-3、Bax mRNA、蛋白表达均降低(P<0.01);与模型组比较,中药、西药组大鼠Caspase-3、Bax mRNA、蛋白表达均增高(P<0.05)。与空白组比较,模型组大鼠食管组织中Bcl-2 mRNA及蛋白表达水平均升高(P<0.05);与模型组比较,中药组和西药组Bcl-2 mRNA及蛋白表达水平均降低(P<0.05)。结论:加味旋覆代赭汤可能通过下调Bcl-2/Bax比值,增加线粒体外膜通透性,释放凋亡因子,激活Caspase-3,使病变组织发生凋亡,扭转食管上皮异型增生,从而起到治疗食管癌前病变的作用。     

金匮肾气丸对雄激素部分缺乏大鼠血清T及睾丸3β-HSD活性表达的影响

目的 探讨金匮肾气丸治疗肾阳虚型中老年男性雄激素部分缺乏的作用机制.方法 取15月龄SD大鼠40只,随机分为模型组和金匮肾气丸低、中、高剂量治疗组,共4组,每组均10只,各组大鼠均给予腹腔注射环磷酰胺混悬液(1ml/kg·d~(-1)),qd,连续5d,造成雄激素部分缺乏模型后,低、中、高剂量组分别给与金匮肾气丸混悬液灌胃,模型组以蒸馏水灌胃,灌胃28d.末次给药24h后处死大鼠,放射免疫法检测血清T水平,免疫组化法测定3β-HSD活性表达.结果 与模型组比较,金匮肾气丸中、高剂量组血清T水平明显升高(P＜0.05);金匮肾气丸各组3β-HSD阳性表达均显著增强(P＜0.01),以中、高剂量组作用最为显著.结论 金匮肾气丸可通过增强睾酮合成通路中关键酶3β-HSD的活性表达来提高睾酮的合成,从而达到治疗雄激素部分缺乏的目的.     

三芪口服液对5/6肾切除大鼠肾组织细胞凋亡的影响

目的：观察中药三芪口服液对5/6肾切除大鼠肾功能及肾组织形态学、肾脏细胞凋亡的影响,探讨三芪口服液延缓肾脏损害的作用机制。方法：按照随机分配原则将SD大鼠分成6组,分别为空白对照组、模型对照组、三芪口服液治疗高剂量组（TMH组）、三芪口服液中剂量组（TMM组）、三芪口服液低剂量组（TML组）、包醛氧淀粉组（B组）。分别给予相应的干预措施后观察各组大鼠一般状况、肾功能以及光镜下肾脏组织变化和细胞凋亡的情况。结果：三芪口服液各剂量组均可降低造模大鼠的血尿素氮和血肌酐水平,中剂量可以提高造模大鼠的红细胞压积,高、中剂量可以降低造模大鼠的血小板水平,治疗前后比较差异有统计学意义（P〈0.05）。三芪口服液还可以减轻肾脏病理损害程度,以及明显降低慢性肾衰竭大鼠的肾脏细胞凋亡率,与包醛氧淀粉组比较,差异有统计学意义（P〈0.05）。结论：三芪口服液能改善慢性肾衰竭大鼠的肾功能及整体机能状态,其作用机制可能是通过改善肾脏微循环,抑制细胞过度凋亡参与的肾脏病理损害等方面实现的。     

前列腺Ⅰ号水丸对慢性细菌性前列腺炎大鼠组织内菌落数量和NO、NOS浓度的影响

目的:探讨前列腺I号水丸对慢性细菌性前列腺炎(CMP)大鼠组织内菌落数量、一氧化氮(NO)浓度和一氧化氮合酶(NOS)活力的影响。方法:健康成年雄性Wistar大鼠120只,体重250~300 g,随机分为6组,分别为空白对照组、模型对照组、阳性对照组、水丸高剂量组、水丸中剂量组、水丸低剂量组,每组20只。前列腺注射大肠杆菌(107个/ml)建立CMP大鼠动物模型。造模成功1个月后,用前列腺水丸高[4.4 g/(kg.day)]、中[2.2 g/(kg.day)]、低[1.1 g/(kg.day)]剂量灌胃治疗,阳性对照组用美满霉素[0.018 g/(kg.day)]灌胃,模型组和空白组用生理盐水灌胃。连续治疗35 d后,计算大鼠前列腺组织匀浆菌落数。采用亚硝酸盐还原酶法检测前列腺组织中NO变化并计算NOS活力的变化。结果:前列腺Ⅰ号水丸高、中、低剂量组大鼠组织内菌落数的水平和前列腺组织内NO含量及NOS活力明显低于模型组,与模型组比较差异显著(P<0.01)。结论:前列腺Ⅰ号水丸对慢性细菌性前列腺炎模型大鼠有一定治疗作用。其作用机制可能与抑制前列腺内细菌生长以及降低前列腺组织内NO含量和NOS活力有关。     

Central nervous system toxicity of cyclosporine in a rat model

The central nervous system toxicity of cyclosporine, which is known to be neurotoxic clinically, was investigated in a rat model. Munich-Wistar rats were divided into 3 groups for a 2-week protocol. After baseline EEG and behavioral testing, group 1 (control) received a weight-adjusted volume of parenteral cyclosporine vehicle i.p., group 2 (low-dose) received 5 or 10 mg/kg/day i.p., and group 3 (high-dose) received 20 mg/kg/day i.p. Spontaneous behavior was observed, simple sensorimotor testing performed daily, and awake EEG's recorded 3 times per week. Four of 12 high-dose animals died during study, one after a witnessed tonic-clonic seizure, and two after recording of frankly epileptiform EEG's; there were no deaths in control or low-dose animals. Significant EEG abnormalities developed only at high-dose, with frankly epileptiform EEG's and/or seizures seen in 58 +/- 15% of these rats (P = 0.005, different from controls by life-table analysis). Although some high-dose animals demonstrated hyperirritability and dystonic posturing, behavioral changes were subtle, and animals were often still or rocking slightly during recording of frankly epileptiform EEG's. Walking latency and alley escape behaviors were delayed in high-dose rats, the latter correlating with abnormal EEG's. Serum urea nitrogens were mildly elevated in high-dose animals, but serum creatinine, electrolytes, bilirubin, body magnesium stores, and blood pressure remained normal in all groups. Kidneys showed only mild vacuolation histologically. The brain showed only very focal cortical injury sites related to electrode placement, which did not correlate with EEG changes or mortality. These results suggest that there may be a direct effect of cyclosporine on the central nervous system. This model system should prove useful in defining mechanisms of cyclosporine-related neurotoxicity.     

金属铬在小鼠血清中的含量变化及对肝脏影响的实验研究

目的通过铬染毒动物模型的制备，探讨人工全髋关节表面置换术后血清铬含量变化和对肝脏功能及器官结构的影响。方法48只ICR小鼠随机分成4组，高、中、低3个剂量组及对照组，剂量组予以重铬酸钾（K2Cr2O7）灌胃染毒，对照组给予双蒸水灌胃，于染毒后48h，1、2、3、5周进行眼球取血测血清铬含量和肝功能，实验小鼠于第5周全部处死，评估肝脏脏器系数的差异以及对其进行光镜和透射电镜的观察。结果染毒48h血清铬浓度升高，染毒1周上升至最高水平，继续染毒至第2、3、5周血清铬含量趋于稳定；ALT、AST、ALP无论在染毒时间上，还是在同一剂量组内比较，其升高均有统计学意义；光镜、电镜下，肝脏出现明显病理损伤变化。结论金属铬离子在血清中有浓度波峰的存在，长期染毒血铬水平趋于稳定；金属铬能长期蓄积在肝脏等器官内，有肝脏毒性。     

线性多肽α3127-148诱导抗肾小球基底膜肾炎大鼠模型的建立

目的以人Ⅳ型胶原α3链非胶原区结构域1[α3(Ⅳ)NC1]上的线性多肽α3127-148作为抗原,建立抗肾小球基底膜(GBM)肾炎大鼠模型。 方法7~8周龄雌性WKY大鼠30只,体重100~150 g,随机分为3组(10只/组)：对照组、低剂量多肽免疫组(低剂量组)、高剂量多肽免疫组(高剂量组)。多肽α3127-148一次性注射于大鼠后足垫来进行建模,低剂量组注射200 μg/kg、高剂量组注射300 μg/kg、对照组仅注射等体积溶剂。每周定时收集24 h尿测尿蛋白浓度。所有动物在第6周末处死,检测血清肌酐和尿素氮。大鼠肾组织切片进行PAS染色、Masson染色及免疫荧光染色。 结果与对照组相比,高剂量组24 h尿蛋白浓度自第3周末开始明显升高(P<0.05),第6周末血清尿素氮和肌酐水平均明显升高(P<0.05),PAS染色可见肾小球硬化、弥漫性新月体形成,荧光染色可见IgG在GBM呈明显线性沉积。与对照组比较,低剂量组第6周末24 h尿蛋白浓度明显升高(P<0.05),PAS染色亦见肾小球有明显损伤,但较高剂量组轻。 结论本研究采用线性多肽α3127-148免疫WKY大鼠,成功地建立了抗GBM肾炎模型,该方法简单、效率高。     

乌司他丁联合抗真菌药物治疗侵袭性念珠菌感染的实验研究

目的探讨乌司他丁联合抗真菌药物治疗侵袭性念珠菌感染的有效性和可能机制。方法雄性昆明小鼠60只,经CTX预处理后腹腔注射白念珠菌混悬液,制作侵袭性念珠菌感染小鼠模型,随机分成对照组（n=20）、低剂量组（n=20）和高剂量组（n=20）。对照组给予抗真菌药物治疗,低剂量组给予抗真菌药物联合乌司他丁（1×104U／kg）治疗,高剂量组给予抗真菌药物联合乌司他丁（5×10^4U／kg）治疗,观察3组7d生存率、肝组织细胞因子和血淋巴细胞亚群水平。结果侵袭性念珠菌感染小鼠模型制作成功。高剂量组第7天生存率显著高于对照组（70％vs30％,P=0．011）。低剂量组和高剂量组第7天肝组织IL-10均显著低于对照组（P〈0．05）。低剂量组和高剂量组第7天小鼠CD4＋／CD8＋比例均显著高于对照组（P〈0．05）。结论高剂量乌司他丁可以改善侵袭性念珠菌感染小鼠7d生存率,机制可能与提高细胞免疫功能和降低免疫抑制的发生有关。     

Sildenafil accelerates liver regeneration after partial hepatectomy in rats

Objective

The regeneration process causes the liver to achieve an adequate volume and function after major hepatectomy or living donor liver transplantation. Sildenafil, a selective phosphodiesterase-5 inhibitor used for erectile dysfunction, impacts the liver by enhancing the effects of nitric oxide. The aim of this study was to investigate the influence of sildenafil on liver regeneration in rats after partial hepatectomy.

Methods

Sixty young female Wistar Albino rats were randomly divided into three equal groups before 70% hepatectomy. Thereafter, we administered intraperitoneal saline to the control group (G1); 10 μg/kg sildenafil to the low-dose group (G2) and 100 μg/kg to the high-dose sildenafil group (G3). Half of the rats per group were sacrificed on the first and the other half on the fifth postoperative day after partial hepatectomy. Regeneration was assessed using three methods: (1) the formula described by Kwon et al formula, (2) the average number of mitotic figures in 10 microscopic fields, and (3) the average of Ki-67-positive nuclei in 1000 cells using immunohistochemistry.

Results

Although, the hepatic regeneration and mitosis rates were similar in all three groups, Ki-67 levels were significantly higher in both G2 and G3 than the control group on the first postoperative day. Hepatic regeneration was significantly greater in G2 and G3 than the control group as was the mitosis rate in the G2 group versus the two groups. By the 5th postoperative day Ki-67 levels were similar in the three groups.

Conclusion

Sildenafil treatment accelerated hepatic regeneration after partial hepatectomy in rats.     

Portal donor-specific blood transfusion and mycophenolate mofetil allow steroid avoidance and tacrolimus dose reduction with sustained levels of chimerism in a pig model of intestinal transplantation

BACKGROUND: In a pig model of intestinal transplantation, we previously showed that hepatic conditioning through portal donor-specific blood transfusion (pDSBT), high-dose tacrolimus (TAC), and steroids prevented rejection and increased survival Our current study tests a protocol of pDSBT, short-term mycophenolate mofetil (MMF), and low-dose TAC to eliminate the use of steroids, reduce TAC dosage, and increase the level of chimerism in the peripheral blood. MATERIALS AND METHODS: Four groups of outbred, mixed lymphocyte culture (MLC)-reactive pigs underwent bowel transplants and pDSBT. Immunosuppression (group 1, high-dose TAC and steroids; group 2, low-dose TAC and MMF; group 3, low-dose TAC, MMF, and aminoguanidine; group 4, low-dose TAC, MMF, and arginine) was discontinued after 28 days. RNA was extracted from intestinal graft and native liver biopsies for cytokine measurements. Chimerism levels were determined using a Q-PCR analysis. RESULTS: Pig survival and death rates due to rejection did not significantly differ between the four groups. Chimerism levels determined by Q-PCR analysis were not different until day 28. After discontinuation of immunosuppression, we noted a trend (P = 0.15) toward higher mean chimerism levels on day 60 for groups 2, 3, and 4 (9%) vs. group 1 (0.5%). Tissue cytokine and serum nitrate levels did not significantly differ between the four groups. Attempts to modify nitric oxide synthase activity offered no added benefit. CONCLUSIONS: The combination of pDSBT, MMF, and low-dose TAC (vs. high-dose TAC and steroids) allowed sustained levels of mixed chimerism to develop after discontinuation of immunosuppression.     

A comparison of heterotopic and orthotopic intestinal transplantation in rats

Two surgical techniques are commonly used for small intestinal transplantation: heterotopic (accessory) intestinal grafting (HIT), where the small bowel is initially defunctioned with restoration of intestinal continuity at a later date, and orthotopic (in continuity) intestinal grafting (OIT), where the small bowel is immediately anastomosed to the native intestine. The present experiments were undertaken to compare the advantages and disadvantages of these two surgical models. Graft barrier function (intestinal permeability), intestinal histology, and graft survival were evaluated after heterotopic and orthotopic intestinal transplantation in the following groups of rats: group 1: isografts, group 2: untreated allografts, group 3: low-dose cyclosporine-treated allografts (subcutaneous CsA 2 mg/kg/day), and group 4: high-dose CsA-treated allografts (subcutaneous CsA 4 mg/kg/day). Intestinal permeability was consistently higher after HIT than OIT in all of the groups (ANOVA; P less than 0.01). Histological evidence of rejection appeared earlier after HIT than OIT (HIT 5th postoperative day (POD); OIT 7th POD; P less than 0.05). The mean survival of untreated allografts was longer after HIT than OIT (HIT 15.7 +/- 6 days, OIT 9.2 +/- 1 days, P less than 0.05). The rats treated with low-dose CsA after OIT lost weight and died of rejection after a mean survival time of 17.7 +/- 2 days, while the rats treated with low-dose CsA after HIT remained well until sacrifice on POD 28 (P less than 0.01). The rats with isografts and rats with allografts treated with high-dose CsA remained well after HIT and OIT until sacrifice on the 28th POD. These data suggest that nutrients and other factors in the succus entericus may improve gut barrier function and delay the onset of rejection after OIT. However, rejection of the orthotopic intestinal graft is usually fatal, while rejection of the heterotopic graft is often surprisingly well tolerated. These factors must be taken into consideration when choosing a surgical technique for intestinal transplantation in humans.     

复方玄驹胶囊对去势雄性大鼠性激素水平及性器官重量的影响

目的:探讨复方玄驹胶囊对去势雄性大鼠性激素水平及性器官重量的影响。方法:采用随机分组、空白对照、模型对照的临床研究方法,从60只SPF级雄性幼年SD大鼠中,随机取出12只大鼠为正常对照组,余大鼠去势(摘除双侧睾丸)后,随机均分4组,分别为模型对照组、复方玄驹胶囊高、中、低剂量组。正常模型对照组予生理盐水灌胃,模型组采用复方玄驹胶囊配制液灌胃干预,20 d后,采用放射免疫法检测各组大鼠外周血液中睾酮(T)、黄体生成素(LH)和卵泡刺激素(FSH)水平,同时称取附睾、包皮腺、精囊腺、前列腺及提肛肌的重量。结果:①与正常对照组相比,去势各组T水平显著降低,说明造模成功。与模型对照组相比,复方玄驹胶囊高、中、低剂量组T水平明显升高,差异有统计学意义(P<0.01)。②与正常对照组相比,模型对照组、复方玄驹胶囊各剂量组LH水平显著升高,差异有统计学意义(P<0.05);FSH水平虽有所升高,但差异无统计学意义。③与正常对照组相比,模型对照组包皮腺、精囊腺、前列腺、提肛肌指数明显降低,说明造模成功;与模型对照组相比,复方玄驹胶囊高剂量组精囊腺指数明显提高,差异有统计学意义(P<0.05);而复方玄驹胶囊不同剂量组之间比较,包皮腺、前列腺、提肛肌指数均未见明显增加,差异无统计学意义(P>0.05)。结论:复方玄驹胶囊可改善雄性SD大鼠外周血中激素水平,提高附性器官指数,可能是临床治疗ED的重要作用机制之一。     

Chemopreventive effects of cyclooxygenase-2 inhibitor and epidermal growth factor-receptor kinase inhibitor on rat urinary bladder carcinogenesis

OBJECTIVE: To examine the chemopreventive effects of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, and a selective epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor, gefitinib (as a single agent) on a carcinogen-induced rodent bladder carcinogenesis model. MATERIALS AND METHODS: The study comprised 103 male Fisher-344 rats (8 weeks old); after initial carcinogen treatment for 8 weeks with 0.05%N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water, the rats were divided into five groups, i.e. group 1, control (vehicle only); group 2, gefitinib high-dose (15 mg/kg by gavage once daily); group 3, gefitinib low-dose (5 mg/kg); group 4, meloxicam high-dose (1.8 mg/kg by gavage once daily); and group 5, meloxicam low-dose (0.6 mg/kg). Twelve weeks later the rats were killed; after fixing the bladder in 10% formalin, the number and size of hyperplasia and carcinoma foci were recorded microscopically in sections stained with haematoxylin and eosin, submitted entirely as multiple strips. RESULTS: The incidence of carcinoma, confirmed microscopically, was: control 14/20 (70%); high-dose gefitinib, 7/20 (35%); low-dose gefitinib, 7/20 (35%); high-dose meloxicam 7/21 (33%); and low-dose meloxicam, 12/20 (60%). The mean numbers of carcinomas per bladder in groups 1-5 were 1.2, 0.5, 0.4, 0.5 and 1.1, respectively. The incidence and the mean number of carcinomas per bladder were significantly lower in the treatment groups (P < 0.05) than in the control group, except in the low-dose meloxicam group. There were no significant adverse effects. CONCLUSION: Both meloxicam and gefitinib have inhibitory effects on rat bladder carcinogenesis with no significant adverse effects. A combination of these drugs would be worth studying for their synergistic effects.