急性弓形虫感染对BALB/c孕鼠胚胎发育的影响

目的观察BALB/c孕鼠胚胎器官发生期急性弓形虫感染对胚胎发育的影响。方法采用整体致畸试验,将受精鼠随机分为阴性对照A组、B1~B4染虫组和环磷酰胺阳性对照C组。孕8 d时A组腹腔注射无菌PBS,B1~B4组分别注射弓形虫速殖子25、50、100、200个/只,C组小鼠注射环磷酰胺20 mg/kg体重。孕18 d处死孕鼠,观察胚胎生长发育状况。结果与A组相比,B2组胎盘、胎鼠重量减轻(P0.05);B3、B4组孕鼠体重、胎盘、胎鼠重量减轻(P0.05),着床数下降(P0.05),活胎率、吸收胎率、死胎率、流产率升高(P0.05),B4组胎鼠畸形率增高(P0.01)。结论 BALB/c小鼠妊娠期急性弓形虫感染可致胎盘功能障碍,胎鼠生长发育缓慢,并出现胎鼠畸形、死胎和流产等病理性妊娠。     

不同方法在先心病室间隔缺损动物模型建立中的对比研究

目的:利用三种不同方法建立先心病室间隔缺损小鼠动物模型,并对其进行相互比较,得出一个简便?效果稳定?可重复性好的CHD动物模型?方法:①VPA动物模型:(1)VPA剂量处理组:对D7孕鼠分别腹腔注射VPA200mg/kg,400mg/kg,600mg/kg,700mg/kg;(2)VPA时间处理组:对D6?D7?D8和D9孕鼠腹腔注VPA700mg/kg,对照组:孕鼠腹腔注射0.9%Nacl?②HCY动物模型:高剂量组[HCY200mg/(kg·d)],低剂量组[HCY100mg/(kg·d)],对照组腹腔注射0.9%Nacl,孕鼠妊娠第7天起每日腹腔注射1次,直至孕第l7天,19天再注射1次?③VAD动物模型:实验组小鼠AIN-76A配方配制饲料,对照组每公斤饲料加入4000IUVA/kg,喂养2.5个月实验组VAD后,与正常饮食雄鼠交配?观察胎鼠心脏畸形发生率?结果:三组动物模型胎鼠心脏畸形发生率实验组均明显高于对照组(p<0.05),以VPA第7天,700mg/kg剂量孕鼠组心脏畸形发生率11.17%为最高?结论:三组动物模型实验组均可致胎鼠心脏发育畸形,以VPA组孕第7天,700mg/kg剂量胎鼠心脏畸形发生率最高?     

孕早期急性感染弓形虫致先天性弓形虫病胎鼠模型的建立

目的建立孕鼠早期急性感染弓形虫RH强毒株致先天性弓形虫病胎鼠模型,观察孕早期母体弓形虫感染对胎鼠脑发育的影响。方法 SD孕鼠42只于胚胎第3天(E3)随机分为对照组、实验组、地塞米松组各14只。对照组注射灭菌PBS,实验组与地塞米松组以腹腔注射弓形虫RH株,后者同时给予地塞米松饮水。分别于胚胎第14、16天(E14、E16)处死孕鼠剖腹取胎鼠,进行胚胎形态学观察;胎盘压片镜下观察弓形虫体;PCR检测各组羊水、胎肝中的弓形虫B1基因;免疫荧光染色检测对照组、实验组及地塞米松组胎鼠不同发育时期脑组织中的Caspase-3、神经元迁移蛋白(DCX)。结果 3组孕鼠均无死亡。实验组、地塞米松组E14、E16胚胎均有出血、坏死和吸收发生,胎鼠无明显肉眼可见畸形,对照组无死胎、吸收胎出现,3组平均活胎率分别为100%、61%、18%,3组平均活胎率相比,P均<0.05。仅地塞米松组在E14一窝别观察到2个胎盘压片有弓形虫体,羊水中检测到B1基因表达。实验组及地塞米松组胎肝中均检测到B1基因表达。E14、E16实验组胎鼠脑组织中Caspase-3表达较对照组明显增强,但较地塞米松组减低(P均<0.05);实验组DCX表达较对照组减弱,较地塞米松组增强(P均<0.05)。结论建立了稳定垂直传播的先天性弓形虫病胎鼠模型,弓形虫对胚胎脑发育具有毒性作用。     

灭螺新药“浸螺杀”对妊娠大鼠及其胚胎的毒性研究

本文观察了浸螺杀4个剂量组,100、50、25及12.5mg/kg/d×7,对大鼠的胚胎毒性作用。浸螺杀以5％吐温液配成相当于现场浸泡杀螺浓度的6000、3000、1500及500倍4种浓度灌胃,阳性对照组以丝裂霉素1.5mg/kg/d,腹腔注射,连续3天。结果:浸螺杀最高剂量100mg/kg/d(合小鼠LD_(50)1/4),浓度为现场灭螺浓度的6000倍的情况下,各实验组结果与阳性对照组相比,无论在孕鼠体重增长、正常胎率与吸收胎率、胎鼠发育等,均无显著差异,内脏及骨骼亦无明显畸形。而阳性对照丝裂霉素组,吸收胎明显增加,出现不同时期的死胎、短尾畸形,说明浸螺杀无明显的胚胎毒性。     

先天性心脏病大动脉转位小鼠模型的建立

目的:尝试建立一种先天性心脏病大动脉转位小鼠模型,为探讨该类疾病发生、发展的相关机制提供条件。方法:20只8~10周大的SPF级ICR孕鼠随机分为对照组(n=5)和实验组(n=15)。实验组孕鼠在E8.5天给予单次剂量全反式视黄酸(70 mg/kg)腹腔注射,对照组孕鼠在E8.5天给予单次剂量二甲基亚砜(70 mg/kg)腹腔注射。注射完毕后继续饲养至E18天后取出胚胎,在体式显微镜下观察心脏表型。结果:与对照组相比,实验组胚胎的早产、流产、胚胎吸收的发生率显著增加;大动脉转位表型明显,发生率为61.2%,同时合并突眼、神经管畸形等多种心外表型发生。结论:全反式视黄酸可以诱导小鼠胚胎发生大动脉转位,是一种可行的疾病动物模型。     

辛酰伯喹对大鼠胚胎毒牲的观察

以辛酰伯喹160mg/kg/d×1、50mg/kg/d×1、16mg/kg/d×1三个剂量,分别于母鼠妊娠第7天(D_7)肌注。另设油剂对照组及阳性对照组(敌枯双)妊娠D_(20)解剖检查胚胎。结果表明:辛酰伯喹各组无论在孕鼠体重、正常胎率、胚胎吸收率及胚胎发育等方面,均无明显异常。未见胎鼠外形、内脏及骨骼畸形。两批实验结果一致。辛酰伯喹最高剂最(160mg/kg/d×1)为临床治疗剂量26倍时,未见明显的胚胎毒性。     

溴乙酰胺对妊娠大鼠及其胚胎的毒性

妊娠6日的大鼠,每日喂溴乙酰胺≥24.8mg/kg(≥1/5LD_(50)),连续12日后,活胎率下降,胎鼠有外观畸形的<8.5％。孕大鼠喂五氯酚钠≥25.1mg/kg(≥1/9LD_(50))连续12日,活胎率较溴乙酰胺组明显降低,外观畸形率(>55％)及骨骼畸形率(>75％)均明显升高。     

氯喹与乙胺嘧啶对孕鼠和胚胎的毒性

10只大鼠经口给氯喹280mg/kg/d×3后,9只中毒死亡.孕鼠于D_8起给氯喹70mg/kg/d×3,其总剂量为临床总剂量的7倍时,有轻度胚胎毒性,表现为活胎率下降及胎仔平均体重减轻。氯喹剂量增至140mg/kg/d×3时,胎仔骨骼畸形发生率为29％(16/55),较对照组的明显为高,P<0.01;若与乙胺嘧啶7mg/kg/d×3(总剂量相当临床总剂量的10.5倍)组相比,后者的胎仔骨骼畸变率69.2％(27/39)与侧脑室扩大率29％(9/31)又明显高于氯喹140mg/kg/d×3(总剂量为临床总剂量的14倍)组。此外,孕鼠服氯喹与乙胺嘧啶后,尚有阴道与眼眶出血等中毒症状。     

弓形虫致鼠胚神经系统畸形中NCAM的表达及青蒿素保护作用的研究

目的探讨弓形虫感染孕早期大鼠致胚胎神经系统畸形的分子机制及青蒿素对胚胎的保护作用。方法将SD孕鼠随机分为对照组、模型组和模型治疗组,各组孕鼠于妊娠第3 d(E3)腹腔注射弓形虫RH强毒株,并分别于E12、E14、E16、E18剖腹取胎鼠,进行形态学观察;PCR法检测羊水中弓形虫B1基因表达,免疫荧光染色观察神经细胞粘附分子(NCAM)在胚胎不同发育时期的神经细胞中的表达规律。结果模型组胚胎发育状况差,活胎率低,为11.82%;PCR检测到模型组胚胎羊水B1基因的表达。对照组和模型治疗组E14、E16鼠胚神经细胞中NCAM呈阳性,模型组染色较其他4组弱。结论 NCAM低表达是神经系统畸形发生的重要因素,青蒿素对鼠胚弓形虫感染有保护作用。     

重组小鼠干扰素-γ对感染弓形虫孕鼠T细胞亚群自然杀伤细胞的影响

目的 探讨重组小鼠γ-干扰素（rmu-IFN-γ）对妊娠期感染弓形虫的小鼠脾脏T细胞亚群和自然杀伤细胞（NK细胞）水平的影响。 方法 20只BALB/c孕鼠随机分为空白对照、感染对照及rmu-IFN-γ治疗组。妊娠第7～9 天孕鼠急性感染弓形虫,rmu-IFN-γ分为2个剂量组（按小鼠体重1 U/g和10 U/g）腹腔注射给药,3 d后每组随机处死5只,取脾细胞,流式细胞术检测T细胞亚群和NK细胞水平。 结果 两种剂量rmu-IFN-γ治疗组CD4+ T细胞水平在妊娠第10、12、14 天高于感染对照组,CD8+ T细胞水平在妊娠第10、14天低于感染对照组,CD4+/CD8+ T细胞比值在妊娠第10、12、14 天高于感染对照组（P<0.05）,孕鼠存活时间长于感染对照组。 结论 注射适量rmu-IFN-γ可改善CD4+/CD8+ T细胞比值,促进NK细胞增殖,提高宿主免疫水平。     

中性粒细胞弹性蛋白酶抑制剂对小鼠实验性结肠炎的作用研究

目的 观察中性粒细胞弹性蛋白酶(NE)抑制剂西维来司他对葡聚糖硫酸钠(DSS)诱导的小鼠实验性结肠炎的作用.方法 26只健康雄性BALB/C小鼠分为正常对照组(6只)、实验对照组(6只,腹腔注射磷酸盐缓冲液,9 d)、低剂量组(7只,腹腔注射西维来司他50 mg/kg,9 d)、高剂量组(7只,腹腔注射西维来司他100 mg/kg,9 d).除正常对照组外,其余小鼠均予5%DSS溶液自由饮用以制备实验性结肠炎模型.实验第10天时处死全部小鼠并取结肠组织,行组织学损伤评分.酶联免疫吸附法检测小鼠血浆及结肠组织培养上清中NE含量.Western印迹法检测远端结肠组织中NE表达水平.结果 实验对照组小鼠结肠组织学损伤评分(12.00±2.45)显著高于正常对照组(1.88±0.83,P＜0.01).低剂量组和高剂量组的结肠组织学损伤评分差异有统计学意义(分别为10.17±1.17和5.00±1.15,P＜0.05),均显著低于实验对照组(P值均＜0.05),但均显著高于正常对照组(P值均＜0.05).实验对照组血浆NE浓度、结肠组织培养上清NE含量、结肠组织中NE表达水平均较正常对照组明显升高(P值均＜0.05);与实验对照组相比,低剂量组稍有降低(P值均＞0.05),但仍高于正常对照组(P值均＜0.05);高剂量组则显著降低(P值均＜0.05),与正常对照组无差异(P值均＞0.05);高剂量组较实验组和低剂量组显著降低(P值均＜0.05).结论 NE抑制剂西维来司他可改善DSS诱导的小鼠实验性结肠炎病理损伤,高剂量应用效果优于低剂量.NE可能参与溃疡性结肠炎的发病.     

Influence of rofecoxib on experimental colonic carcinogenesis in rats.

AIM: To investigate the effect of a selective cyclooxigenase-2 (COX-2) inhibitor, rofecoxib, in the prevalence of experimental colon tumors in rats. EXPERIMENTAL DESIGN: Experimental study with 35 male Sprague-Dawley rats, divided into four groups: a) control group without experimental manipulation (n = 5); b) pharmacological carcinogenesis with 1-2 dimethylhydrazine dihydrocloride (n = 10); c) pharmacological carcinogenesis and addition of acetylsalicylic acid (AAS) (n = 10); and d) carcinogenesis and addition of rofecoxib (n = 10). Carcinogenesis was induced with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks. Colon tumors were isolated at 20 weeks. Antiinflammatory agents were given at a dose of AAS 30 mg/kg and rofecoxib at 3 mg/kg. RESULTS: The percentage of colonic tumors was significantly reduced in the rofecoxib group. This result was found for all tumors and for the malignant lesions, adenocarcinomas. CONCLUSIONS: Rofecoxib, a selective COX-2 inhibitor, reduced the percentage of drug-induced neoplastic glandular tissue in rats.     

落新妇甙对热缺血再灌注损伤肝脏肿瘤坏死因子α与白细胞介素-10表达的影响

目的 观察落新妇甙对热缺血再灌注(I/R)损伤肝脏Th1、Th2型细胞因子表达的影响. 方法 C57BL/6小鼠随机分为4组:假手术组、模型组,落新妇甙小剂量(10 mg/kg)干预组和大剂量(40mg,/kg)干预组.干预组小鼠于缺血前24h和1 h分别给予10mg/kg或40mg/kg的落新妇甙腹腔注射,建立70%部分肝I/R模型.收集肝组织标本,Western blot检测肝组织中肿瘤坏死因子(TNF)α,白细胞介素(IL)-10蛋白含量,RT-PCR检测肝组织TNF α、IL-10 mRNA的水平.多组间比较采用单因素方差分析,两两比较采用SNK法.结果 与I/R模型对照组比较,小、大剂量落新妇甙干预组肝组织中TNF α蛋白表达水平依次降低,与TNF α mRNA的半定量RT-PCR结果 相符(相对表达量分别为1.74±O.12与1.56±0.09、0.82±0.12,P值均<0.05);而IL-10蛋白表达水平依次升高,与IL-10 mRNA的半定量RT-PCR结果 相符(相对表达量分别为0.96±0.08与1.11±0.17、1.47±0.08,P值均<0.05).结论 落新妇甙干预能抑制I/R损伤肝组织中Th1型细胞因子TNFα的高表达,同时促进Th2型细胞因子IL-10的表达.     

知母百合与厄贝沙坦联合运用对高血压大鼠血压和血流动力学的影响

目的观察中药方剂知母百合与厄贝沙坦联合运用对高血压大鼠的血压和血流动力学的影响。方法采用自发性高血压大鼠(SHR)和肾血管狭窄性高血压大鼠(RVHR)模型,将高血压大鼠随机分成4组:对照组(CMC溶剂,n=10)、厄贝组(厄贝沙坦40mg/kg,n=10)、联合组(厄贝沙坦40mg/kg加知母百合浓缩药粉1250mg/kg,n=10)及中药组(知母百合浓缩药粉1250mg/kg,n=10)。动态观察灌胃给药后以下指标的变化:清醒状态下的SHR和RVHR的收缩压(SBP)、舒张压(DBP)、脉压(PP)及收缩压变异率(SBPV)变化;SHR的左心室收缩末期内压(LVESP)、左心室舒张末期内压(LVEDP)、心室内压最大上升速率( dp/dtmax)、心室内压最大下降速率(-dp/dtmax)的变化。结果在SHR和RVHR急性清醒测压中,厄贝组及联合组的SBP及DBP较给药前均明显降低,下降幅度可达20mmHg～28mmHg(1mmHg=0.133kPa,P<0.05);与对照组相比,两组SBP及DBP降低幅度为19mmHg～28mmHg(P<0.05);联合组与厄贝组相比,SBP和DBP降低幅度为6mmHg～9mmHg(P<0.05)。不论给药前后或者与对照组相比,中药组的血压参数无统计学意义(P>0.05)。在SHR的血流动力学实验中,厄贝组及联合组的SBP及DBP较对照组明显下降(15mmHg～24mmHg,P<0.05);各组之间的LVESP、LVEDP、 dp/dtmax、-dp/dtmax无统计学意义(P>0.05)。结论常规剂量的知母百合本身没有降压作用,对大鼠心脏的血流动力学也没有明显影响,但可协同厄贝沙坦的降压作用(幅度6mmHg～9mmHg)。     

白芍总甙对大鼠实验性结肠炎Th17细胞相关因子的作用

目的:观察白芍总甙(TGP)对实验性结肠炎干预的治疗效果,探讨TGP对实验性结肠炎的抗炎作用.方法:40RSD大鼠以三硝基苯磺酸(TNBS)/醇溶液灌肠诱导结肠炎模型,均分为结肠炎模型组、正常对照组(0.9%NaCl溶液灌肠)、TGP组(100mg/kg)和5-ASA药物对照组(100mg/kg).连续灌胃14 d后行结肠大体损伤指数(CMDI)和组织学损伤指数(TDI)评分,ELISA检测血清IL-6、IL-17及IL-23水平,免疫组织化学SP法检测结肠组织TGF-β1与Foxp3的表达.结果:与结肠炎模型组相比,正常组CMDI、TDI,血清IL-6,IL-17及IL-23含量明显低,结肠组织TGF-β1和Foxp3含量明显高.5-ASA与TGP能显著降低CMDI和TDI(2.78分±2.11分,3.56分±1.94分 vs 6.88分±0.84分,均P<0.05;2.22分±0.83分,2.44分±1.51分 vs 5.63分±0.74分,均P<0.05),降低血清IL-6,IL-17和IL-23含量(5-ASA:t=5.998,2.438,2.670,均P<0.05;TGP:t=5.203,3.013,2.962,均P<0.05).升高结肠组织中TGF-β1和Foxp3(5-ASA:t=6.026,3.022,均P<0.05;TGP:t=6.198,2.734,均P<0.05).TGP组与5-ASA组无明显统计学差异.结论:TGP可能通过上调TGF-β1和Foxp3水平,促进Treg细胞的表达,抑制Th17细胞群的活化,下调IL-6,IL-17和IL-23的表达,减轻TNBS诱导的大鼠实验性结肠炎的症状和结肠炎性损伤.     

Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings

PURPOSE: We investigated whether dantrolene might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), using an experimental model in rats. METHODS: Twenty-eight rats were randomized to treatment with saline only (control group, n=8), ISO only (ISO group, n=8), low-dose dantrolene (LDD)+ISO (LDD group, n=6) and high-dose dantrolene (HDD)+ISO (HDD group, n=6). ISO (150 mg/kg/day, s.c.), LDD (5 mg/kg/day, i.p.) and HDD (10 mg/kg/day, i.p.) were given once a day for two consecutive days. At the end of the second day, blood samples were taken from abdominal aorta shortly after the rats were anesthetised for cardiac troponins T (cTnT) and I (cTnI) assay, and the hearts were removed and observed microscopically. RESULTS: cTnT and cTnI levels were increased in the ISO group when compared with the control group (p<0.001). LDD and HDD significantly reduced cTnT and cTnI levels when compared with the ISO group. Elevations of cTnT and cTnI appeared to relate to the severity of histological changes. The rate of animals that exhibited marked MI was higher in the ISO group than in the control group (p<0.001). The rats in both LDD and HDD groups showed less histological changes when compared to the ISO group (p<0.01). There was no significant difference between the control group and both LDD and HDD groups. CONCLUSIONS: This study shows that dantrolene has a significant effect in the protection of the heart against MI induced by ISO. We believe that pretreatment with dantrolene may contribute to developing novel strategies in the cardiotoxicity animal models and in the prevention of the cardiotoxic effects of elevated levels of catecholamines.     

阿司匹林预处理对大鼠局灶性脑缺血的神经保护作用

目的:探讨阿司匹林预处理对缺血性脑损伤的保护机制及最佳剂量。方法:将36只健康雄性 SD大鼠,随机分为假手术组(n=6)、缺血对照组(n=6)和阿司匹林预处理组(n=24)。阿司匹林预 处理组分为5、15、45和150mg/kg4个剂量组(每组6只)。以线栓法闭塞大脑中动脉制作脑缺血模 型。24h后进行神经功能评分并断头取脑制备组织匀浆测定一氧化氮合酶(NOS)活性。结果:阿司 匹林5mg/kg组和15mg/kg组的神经功能评分优于缺血对照组(P<0.01);NOS活性低于缺血对照 组(P<0.01)。阿司匹林45mg/kg组和150mg/kg组在神经功能评分及NOS活性方面与缺血对照 组无显著差异(P>0.05)。结论:阿司匹林预处理对随后的缺血性脑损伤具有保护作用,其机制可能 是抑制NOS活性,减少NO释放。最佳剂量为5mg/kg。     

Laser-induced thrombus formation in mouse brain microvasculature: effect of clopidogrel

Antiplatelet drugs have been evaluated by measuring platelet aggregation ex vivo, but in vivo studies were scanty. The purpose of this study was to observe the effects of an antiplatelet agent (clopidogrel) on the process of laser-induced thrombus formation in mice using intravital fluorescence microscopy. C57 BL/6J mice (n = 19) were anesthetized using chloral hydrate. The head of each mouse was fixed with a head holder, and a cranial window was made in the parietal region. Platelets were labeled in vivo by intravenous administration of carboxyfluorescein diacetate succinimidyl ester. Clopidogrel (1 mg/kg, n = 6; 10 mg/kg, n = 6) was administered orally for 2 days before the experiment. Another seven mice were used as controls. Laser irradiation (1,000 mA, 9.8 mW, diode-pumped solid-state (DPSS) laser 532 nm) was directed for 4 s at pial arteries to induce thrombus formation. Labeled platelets and thrombus were observed continuously under fluorescence microscopy. We recorded the area of thrombus after 30 min and determined the complete occlusion rate. After laser irradiation to the pial artery, complete occlusion rate was significantly lower in the clopidogrel (10 mg/kg) group (16%, 4/25 vessels) than in the control group (60%, 12/20 vessels) or clopidogrel (1 mg/kg) group (55%, 11/20 vessels). Area of platelet thrombus at 30 min after laser irradiation was significantly smaller in the clopidogrel (10 mg/kg) group (209 ± 128 μm(2)) than in the control group (358 ± 256 μm(2)) or clopidogrel (1 mg/kg) group (355 ± 57 μm(2)). The apparatus which we developed is convenient for inducing thrombus formation by causing endothelial cell damage to the brain surface vasculature in small animals without damage of extravascular tissue. Clopidogrel significantly inhibited laser-induced thrombus formation in pial arteries of mice in a dose-dependent manner.     

链霉蛋白酶对胃组织中治疗幽门螺杆菌药物浓度的影响

目的 明确链霉蛋白酶应用对胃组织中阿莫西林和甲硝唑浓度的影响.方法 C57BL/6小鼠随机分为实验组和对照组(每组70只),给予奥美拉唑(138.2 mg/kg)+阿莫西林(28.6 mg/kg)+甲硝唑(22.5 mg/kg),并分别予链霉蛋白酶(110 mg/kg)或等量的无菌PBS,上述药物灌胃1次,给药后15～360 min共10个时间点(每组7只/时间点)取血浆和胃组织,高效液相色谱法检测阿莫西林和甲硝唑浓度,并检测给药后120、360min的胃组织黏膜层胃炎指数(HE法)和黏蛋白5AC的相对表达量(蛋白质印迹法).结果 阿莫西林和甲硝唑的胃组织浓度达峰时间早于在血浆出现的时间(均为15 min比60 min),实验组的胃组织浓度明显高于对照组(P＜0.05),主要集中在15～90 min.实验组药物血浆浓度在15和30 min较对照组高(P＜0.05).给药后120、360 min,实验组与对照组的胃黏膜层胃炎指数的差异均无统计学意义(0.28±0.18比0.14±0.14,P＞0.05;0.43 ±0.20比0.28 ±0.18,P＞0.05);黏蛋白5AC的相对表达量实验组较对照组低(0.036 ±0.006比0.197±0.058,P＜0.05;0.039±0.008比0.208±0.072,P＜0.05).结论 链霉蛋白酶明显增加了抗菌药物从胃腔向胃黏膜方向的弥散量,使局部胃组织和血浆浓度升高,且以局部胃组织浓度升高为主,持续时间更长.

Abstract：

Objective To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. Methods C57BL/6 mice were randomly divided into experimental group ( n = 70 ) and control group ( n = 70 ) . Amoxicillin ( 28. 6 mg/kg ) , metronidazole ( 22. 5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa ( hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5 AC (Western blot) were detected at 120 min and 360 min after administration. Results The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P ＜0. 05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control ( P ＜ 0. 05 ). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28±0. 18 vs 0. 14 ±0. 14,P＞0.05; 0. 43 ±0. 20 vs 0. 28 ±0. 18,P ＞0. 05). The expressions of mucin 5 AC in experimental group were lower than those of control ( 0. 036 ± 0. 006 vs 0. 197 ± 0. 058; P ＜0. 05; 0. 039 ± 0. 008 vs 0. 208 ± 0. 072, P ＜ 0. 05 ). Conclusions Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time.     

Synergistic action of famotidine and chlorpheniramine on acetic acid-induced chronic gastric ulcer in rats

AIM: To assess the synergistic action of famotidine (FMD) and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats. METHODS: Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n=8), control group (n=8), FMD group (n = 8), CPA group (n=8), and FMD+CPA group (n=8). Each group was given intraperitoneally (i.p.) 0.5 mL/100 g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10 mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively, daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenation was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGFia) and IL-8 were determined by radioimmunoassay. RESULTS: The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGFia and MPO were confirmed. The effect of FMD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm2) was reduced from 40.18±2.6 in control group to 6.83±2.97 in PMD+CPA group, P<0.01, and from 32.9±3.27 in FMD group to 6.83±2.97 in PMD+CPA group, P<0.01. The plasma levels of IL-8 decreased from 0.69±0.11 ng/L in control group to 0.4±0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51±0.08 ng/L in FMD group to 0.4±0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGFia increased from 7.55±1.65 ng/L in control group to 16.62±0.97 ng/L in PMD+CPA group, P<0.01, and from 13.15±1.48 ng/L in FMD group to 16.62±0.97 ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12±2.05 u/L in control group to 4.33±0.95 u/L in PMD+CPA group, P<0.01, and from 8.3±1.29 u/L in FMD group to 4.33±0.95 u/L, P<0.01. CONCLUSION: The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the healing of ulcer.