复方乌金汤对急性肝损伤大鼠肝脏保护作用的研究

目的:观察复方乌金汤对急性肝损伤大鼠肝脏的保护作用。方法:SD大鼠随机分为正常组、模型组、水飞蓟素组和复方乌金汤治疗组,采用内毒素联合D-氨基半乳糖腹腔注射诱导急性肝损伤大鼠模型,分别于造模后6、24、48小时处死大鼠,全自动生化仪检测其血清ALT、AST水平,鲎试剂反应动态比浊法检测血浆内毒素含量,观察各组大鼠肝脏病理学变化。结果:复方乌金汤能降低急性肝损伤大鼠血清ALT和AST水平,改善大鼠肝脏病理学变化,减少血浆内毒素含量。结论:复方乌金汤对急性肝损伤具有较好的保护作用。     

卡托普利与水飞蓟宾联用对大鼠酒精性脂肪肝的作用及抗氧化应激机制

目的:研究卡托普利与水飞蓟宾联合用药对大鼠酒精性脂肪肝的作用以及其抗氧化应激机制。方法:SD大鼠造模后随机分为模型组、卡托普利13. 5 mg/kg组、水飞蓟宾37. 8 mg/kg组以及联合用药组(卡托普利13. 5 mg/kg+水飞蓟宾37. 8 mg/kg),另设正常对照组,第12周末腹主动脉取血,检测血清ALT、AST,肝组织称重检测肝脏指数,制备10%肝匀浆检测各组大鼠TG、TC、MDA、GSH-Px含量及CYP2E1蛋白表达。结果:模型组大鼠肝脏指数、TG、TC、ALT、AST、MDA含量及CYP2E1蛋白表达量明显高于正常组,GSH-Px含量明显低于正常组;卡托普利组、水飞蓟宾组、联合用药组大鼠的肝脏指数、TG、TC、ALT、AST、MDA含量及CYP2E1蛋白表达明显低于模型组,GSH-Px含量明显高于模型组;联合用药组大鼠肝脏指数、TG、TC、ALT、AST、MDA含量、CYP2E1表达明显低于卡托普利组和水飞蓟宾组,GSH-Px含量明显增高。结论:联合用药组能够改善酒精性脂肪肝且比单独使用卡托普利组、水飞蓟宾组效果好。     

水飞蓟宾明胶微球在大鼠体内的药动学及组织分布

目的:研究水飞蓟宾明胶微球在大鼠体内的药动学及组织分布.方法:以水飞蓟宾注射液为参比,用3P 97软件计算药动学模型及药动学参数,用靶向效率来评价其在大鼠体内的组织分布及靶向性.结果:水飞蓟宾明胶微球在大鼠体内的药动学模型符合二室模型,主要药动学参数为:t1/2α=(0.5728±0.108 6)h,t1/2β=(20.6866±1.058 8)h,CL=(0.003 8±0.001 4) mL·h· Kg-1,AUCo→∞=(211.095 0±10.272 8) mg·h·L-1,其在肝脏、脾脏、心脏及肾脏的靶向效率分别为2.093,1.986,0.634,0.259.结论:与水飞蓟宾注射液相比,水飞蓟宾明胶微球能提高对肝脏,脾脏的趋向性,有利于提高其治疗作用.     

西洋参胶囊对手机频率电磁辐射大鼠肝脏组织氧化损伤及Nrf2蛋白表达的影响

目的观察西洋参胶囊对900 MHz手机频率电磁辐射大鼠肝脏组织氧化损伤和肝Nrf2蛋白表达的影响。方法40只雄性SD大鼠随机分为正常组、模型组、水飞蓟宾组和西洋参组,每组10只。正常组不接受辐射,模型组、水飞蓟宾和西洋参组每天暴露于900 MHz手机频率辐射4 h,连续12天。水飞蓟宾组和西洋参组辐射同时分别灌服水飞蓟宾胶囊混悬液和西洋参胶囊混悬液（1 mL/200 g体重）,正常组和模型组每日灌服生理盐水。采用HE染色观察肝脏组织形态学变化,比色法检测大鼠肝组织MDA、SOD、GSH、GSH-PX含量,免疫组化法、Western blot 检测大鼠肝Nrf2蛋白表达。结果与正常组比较,模型组大鼠肝细胞核缩小或部分消失,肝组织MDA含量及Nrf2蛋白表达升高（P〈0.05,P〈0.01）,SOD、GSH含量降低（P〈0.05）。与模型组比较,水飞蓟宾和西洋参组大鼠肝细胞核固缩均明显减轻,接近正常;水飞蓟宾组MDA含量及Nrf2蛋白表达降低（P〈0.05）,SOD、GSH、GSH-PX含量升高（P〈0.05）;西洋参组MDA含量及Nrf2蛋白表达降低（P〈0.05）,SOD、GSH含量显著性增加（P〈0.01,P〈0.05）。结论900 MHz手机频率电磁辐射可影响大鼠肝细胞Nrf2表达,致氧化损伤,引起肝细胞形态异常;水飞蓟宾和西洋参可促进肝细胞形态的修复,其机制可能与影响大鼠肝细胞Nrf2表达,减轻氧化损伤有关。     

西洋参胶囊对手机频率电磁辐射大鼠肝脏组织氧化损伤及Nrf2蛋白表达的影响北大核心CSCD

目的观察西洋参胶囊对900MHz手机频率电磁辐射大鼠肝脏组织氧化损伤和肝Nrf2蛋白表达的影响。方法 40只雄性SD大鼠随机分为正常组、模型组、水飞蓟宾组和西洋参组,每组10只。正常组不接受辐射,模型组、水飞蓟宾和西洋参组每天暴露于900MHz手机频率辐射4h,连续12天。水飞蓟宾组和西洋参组辐射同时分别灌服水飞蓟宾胶囊混悬液和西洋参胶囊混悬液(1mL/200g体重),正常组和模型组每日灌服生理盐水。采用HE染色观察肝脏组织形态学变化,比色法检测大鼠肝组织MDA、SOD、GSH、GSH-PX含量,免疫组化法、Western blot检测大鼠肝Nrf2蛋白表达。结果与正常组比较,模型组大鼠肝细胞核缩小或部分消失,肝组织MDA含量及Nrf2蛋白表达升高(P<0.05,P<0.01),SOD、GSH含量降低(P<0.05)。与模型组比较,水飞蓟宾和西洋参组大鼠肝细胞核固缩均明显减轻,接近正常;水飞蓟宾组MDA含量及Nrf2蛋白表达降低(P<0.05),SOD、GSH、GSH-PX含量升高(P<0.05);西洋参组MDA含量及Nrf2蛋白表达降低(P<0.05),SOD、GSH含量显著性增加(P<0.01,P<0.05)。结论900MHz手机频率电磁辐射可影响大鼠肝细胞Nrf2表达,致氧化损伤,引起肝细胞形态异常;水飞蓟宾和西洋参可促进肝细胞形态的修复,其机制可能与影响大鼠肝细胞Nrf2表达,减轻氧化损伤有关。     

蛇床子素在正常与急性肾功能衰竭兔体内的分布研究

目的:正常与急性肾功能衰竭兔iV给药后,比较研究蛇床子素在兔体内的动态定量分布特点.方法:蛇床子素iv给药后,分时采集血样,断头处死动物,取出心脏、肝脏、肾脏、脑组织并制备匀浆,以HPLC法测定血浆及组织中蛇床子素的含量.结果:iv给药后,以同一器官不同时间药物的平均含量占总量百分比的多少表示,蛇床子素在正常兔体内的分布依次为血液＞心脏＞肾脏＞脑＞肝脏.而在肾衰兔体内的分布为血液＞肾脏＞心脏＞脑＞肝脏,与正常组相比,蛇床子素在肾衰兔体内血液、肾脏中含量显著升高(P＜0.05),而在心脏、脑、肝脏组织的含量显著降低(P＜0.05).结论:蛇床子素在正常与肾衰兔体内组织中的含量分布有明显区别.     

水飞蓟宾对离体心脏缺血再灌注损伤保护作用及机制

目的研究水飞蓟宾对Langendorff灌流大鼠离体心脏缺血再灌注损伤的保护作用并探讨其机制。方法将100只雄性SD大鼠随机分为正常组、模型组、水飞蓟宾低剂量组、水飞蓟宾中剂量组、水飞蓟宾高剂量组,每组20只。手术前2 h,正常组、模型组灌胃生理盐水,水飞蓟宾各组分别给予水飞蓟宾100 mg/(kg·d)、200 mg/(kg·d)、400 mg/(kg·d)灌胃。采用Langendorff灌流系统制备大鼠离体心脏灌注模型,模型组与水飞蓟宾各组灌注K-H液20 min后停灌30 min,然后再灌注60 min,正常组持续灌注K-H液。灌注结束后测定各组冠脉流出液中心肌酶谷草转氨酶(AST)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性,通过生物信号采集系统监测离体心脏血流动力学指标,通过TTC染色计算心肌梗死面积,采用HE染色观察心肌组织病理学变化,采用紫外-可见分光光度计测定心肌组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、Na~+-ATPase、Ca~(2+)-ATPase活力及丙二醛(MDA)含量。结果模型组冠脉流出液中AST、LDH、CK-MB活性及离体心脏梗死面积均显著高于正常组(P均0.05),而水飞蓟宾中、高剂量组AST、LDH、CK-MB活性及离体心脏梗死面积均显著低于模型组(P均0.05)。模型组大鼠离体心脏血流动力学指标心率(HR)、左室收缩压(LVSP)、左室收缩压最大上升速率(+dP/dtmax)、左室舒张压最大下降速率(-dP/dtmin)均显著低于正常组(P均0.05),左室舒张末压(LVEDP)显著高于正常组(P0.05);水飞蓟宾中、高剂量组HR、LVSP、+dP/dtmax、-dP/dtmin均显著高于模型组(P均0.05),LVEDP显著低于模型组(P0.05)。水飞蓟宾各组大鼠离体心脏组织病变轻于模型组,其中水飞蓟宾高剂量组病变最轻。模型组大鼠离体心脏组织中SOD、CAT、Na~+-ATPase、Ca~(2+)-ATPase活性显著低于正常组(P均0.05),MDA含量显著高于正常组(P0.05);水飞蓟宾中、高剂量组SOD、CAT、Na~+-ATPase、Ca~(2+)-ATPase活性显著高于模型组(P均0.05),MDA含量显著低于模型组(P均0.05)。结论水飞蓟宾对离体心脏缺血再灌注损伤具有一定的保护作用,机制可能与其能够改善血流动力学、抑制氧化应激、提高ATP酶活力有关。     

注射用水飞蓟宾葡甲胺盐在大鼠体内药动学及组织分布的研究

目的:明确注射用水飞蓟宾葡甲胺盐在大鼠体内的药动学过程及其组织分布规律。方法:大鼠静脉注射高、中、低三个剂量的水飞蓟宾葡甲胺盐,采集血液及组织样品,处理后经高效液相色谱法测定水飞蓟宾葡甲胺盐血浆浓度及组织匀浆液浓度,采用药动学软件3P97进行数据处理,确定药动学参数;通过超滤法测定水飞蓟宾葡甲胺盐在大鼠血浆中的蛋白结合率。结果:水飞蓟宾葡甲胺盐给药后在体内符合二室模型分布,其主要药动学参数分别如下:高剂量:t1/2=38.061min,AUC=1 868.367min/μg/ml,CLs=0.026 1ml/min,K10=0.018;中剂量:t1/2=24.148min,AUC=1 427.284min/μg/ml,CLs=0.041ml/min,K10=0.028;低剂量:t1/2=20.640min,AUC=452.248min/μg/ml,CLs=0.037ml/min,K10=0.033;不同剂量水飞蓟宾葡甲胺盐与大鼠血浆中蛋白的结合率分别是:高剂量:(70.53±0.01)%,中剂量:(72.02±0.02)%,低剂量:(73.43±0.01)%;水飞蓟宾葡甲胺盐在体内分布的最高浓度的大小顺序为肺、肝、心、肾、脾。结论:水飞蓟宾葡甲胺盐在体内呈现非线性动力学消除过程,且体内分布快,起效迅速,消除也快,体内滞留时间短。水飞蓟宾葡甲胺盐属于中蛋白结合率药物,不随剂量变化而变化。水飞蓟宾葡甲胺盐在肺中分布最多,而肝脏中较多。     

古日古木单复方对慢性酒精性肝纤维化大鼠相关炎性因子及Bcl-2、Bax表达的影响

目的研究蒙药古日古木-13和古日古木对慢性酒精性肝纤维化大鼠相关炎性因子及Bcl-2、Bax表达的影响及其作用机制。方法将Wistar大鼠随机分9组(对照组,模型组,古日古木高、中、低剂量保护组,古日古木-13高、中、低剂量保护组,水飞蓟宾胶囊阳性对照组)。模型组灌胃体积分数为0.45的乙醇溶液制作慢性酒精性肝损伤模型,除正常组外其余各给药组大鼠每日分别灌胃体积分数为0.45的乙醇溶液和对应浓度的药液,24周后检测大鼠血清中ALT、AST含量,取部分肝脏作HE染色进行病理组织学检查,检测肝匀浆中MDA含量以及SOD活性。结果模型组与古日古木-13和古日古木高剂量组相比较,血清白蛋白含量明显降低(P0.05),TNF-α和IL-6活性明显升高(P0.05);与正常组相比,酒精性肝损伤模型组的Bax表达明显升高(P0.05),Bcl-2表达明显降低(P0.05)。结论蒙药古日古木-13和古日古木能降低酒精性肝纤维化大鼠的TNF-α和IL-6活性,并能提高肝脏代谢能力、影响凋亡调控蛋白Bcl-2和Bax的表达。     

解毒护肝汤对药物性肝损伤大鼠MMP-2蛋白表达的影响

目的通过检测大鼠血清肝功能指标、血清生物标志物、MMP-2蛋白表达,观察解毒护肝汤对药物性肝损伤大鼠的干预作用及作用机制。方法将大鼠按体质量随机分为正常组、模型组、水飞蓟宾阳性对照组、解毒护肝汤高、中、低剂量组。其中模型组和各给药组给予对乙酰氨基酚药液灌胃复制肝损伤模型,正常组和模型组给予生理盐水灌胃,其余各组给予相应药液灌胃,连续给药30 d。实验结束时,检测谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)、苹果酸脱氢酶(MDH)、对氧磷酶(PON1)、嘌呤核苷磷酸化酶(PNP)含量变化以及肝组织基质金属蛋白酶2(MMP-2)的蛋白表达情况。结果对乙酰氨基酚大鼠血清AST、ALT、DBIL、PON1、MDH、PNP含量均显著升高(P<0.05,P<0.01),解毒护肝汤中、低剂量组能明显降低转氨酶活性及胆红素含量(P<0.05,P<0.01),高剂量组能显著降低肝损伤大鼠血清PON1、MDH含量(P<0.05),中剂量组明显降低MDH的含量(P<0.05)。肝损伤大鼠MMP-2蛋白阳性表达增多;水飞蓟宾胶囊,对照组以及解毒护肝汤各剂量组阳性表达明显减少。结论解毒护肝汤对APAP所致的药物性肝损伤具有防治作用。     

Short term toxicity of embelin in female rats

The toxicity of emblin has been assessed in female cyclic rats. Its administration at a dose of 120 mg/kg body weight did not cause any changes in the weight of liver, kidney and spleen, however, the wet weight of the adrenals showed a remarkable increase. Biochemical constituents such as protein and glycogen did not show any change in these organs except in the adrenal where a significant increase was observed. The activity of acid and alkaline phosphatase was increased in the kidney and adrenal. Administration of embelin for 6 weeks caused severe pathological changes in the liver and kidney which mainly included disintegration, necrotic changes and perinuclear vacuolation. Marked tubular damage was observed in the kidneys. The adrenals showed hypertrophy and the histological features of the spleen remained unchanged.     

Toxic effects of Francoeuria crispa in rats

The toxicity to rats of Saudi Francoeuria crispa used in traditional medicine for the treatment of various disorders was investigated. Francoeuria crispa leaves were fed to rats at 2% and 10% of the diet for 8 weeks. In rats on the 10% F. crispa diet, there was a decrease in average body weight gain and feed efficiency, soft faeces and enterohepatonephrotoxicity. These changes were accompanied by raised serum AST and GGT activities and urea and cholesterol concentrations, decreased total protein and albumin levels, leucopenia and normocytic normochromic anaemia. Growth of rats on the 2% F. crispa diet was promoted compared with rats on a control diet. Copyright © 1998 John Wiley & Sons, Ltd.     

娑罗子抑制胃酸分泌的实验研究

采用幽门结扎法、胃瘘法研究了娑罗子水煎剂对胃酸分泌的影响。结果表明，娑罗子可明显抑制幽门结扎大鼠及胃瘘大鼠的胃酸分泌，连续给药５日后，第６日仍可抑制胃瘘大鼠的胃液分泌量，降低总酸排出量。     

HPLC测定大鼠脑脊液中梓醇的含量

目的:建立大鼠脑脊液中梓醇的含量测定方法.方法:大鼠按5.0 mg·kg~(-1)尾静脉注射1.0 g·L~(-1)梓醇生理盐水注射液,40 min后,经大脑蛛网膜下腔抽取脑脊液;另抽取正常大鼠脑脊液作为空白对照,置-20℃冰箱保存备用.样品经处理后用HPLC检测.选用Hypersil C_(18)反相色谱柱,流动相为水-乙腈(99.5:0.5),流速1.0 mL·min~(-1),检测波长210 nm.结果:脑脊液中梓醇在0.5～40 mg·L~(-1)浓度线性关系良好,r=0.999 7;测得低、中、高浓度绝对回收率为(90.2±1.71)%,(89.1±1.17)%,(86.9±0.98)%;方法回收率为(99.8±1.98)%,(101.1±3.04)%,(100.1±2.30)%;日内、日间精密度均小于4%,在-20℃下冷冻保存15 d稳定.结论:本方法操作简便,能较准确的测出脑脊液中的梓醇含量.     

Subchronic toxicity study of corn silk with rats

Aim of this study

Corn silk is a traditional herbal medicine in China, which has been used in many parts of the world for the treatment of edema as well as for cystitis, gout, kidney stones, nephritis, prostatitis and similar ailments. However, there is little scientific evidence about its safety. As a part of its safety assessment, a subchronic toxicity was performed in this paper.

Methods

The subchronic toxicity was investigated in male and female Wistar rats by dietary administration at concentrations of 0.5%, 2.0% and 8.0% (w/w) for 90 days. Overall health, body weight, food consumption, hematology, blood chemistry, organ weights, gross and microscopic appearance of tissues were compared between test and control groups.

Results

A number of significant differences were seen between groups, but none of them was considered to be adverse. Based on the present study, the no-observed-adverse-effect level (NOAEL) of corn silk is at least 8.0% which corresponds to a mean daily corn silk intake of approximately 9.354 and 10.308 g/day/kg body weight for males and females, respectively.

Conclusion

The results obtained in the present study suggest that consumption of corn silk has no adverse effects and support the safety of corn silk for humans.     

Toxic and hypericaemic effects of Opuntia megacantha extract in rats

The effect of O. megacantha extract on blood uric acid levels and other biochemical profiles were investigated over a 5 week period of giving rats an oral dose of 20 mg/100 g body weight of the extract daily. The results show that O. megacantha extract significantly lowered (p <0.01) serum uric acid and increased renal excretion of uric acid by comparison with controls. Serum creatinine, AST (aspartate aminotransferase) and phosphate levels were significantly raised (p <0.05) in the experimental group. However serum magnesium, calcium and ALP (alkaline phosphatase) were lowered (p <0.05) in the same group by comparison with control rats. An increase (p <0.05) in total water intake, an increase (p <0.05) in total urinary uric acid excretion as well as a slight increase in total urine voided over the 5 week period were observed. © 1997 John Wiley & Sons, Ltd.     

软肝化纤丸对大鼠长期毒性实验研究

[目的]观察大鼠连续灌胃给予软肝化纤丸26周后的毒性反应及毒性程度.[方法]连续灌胃给予SD大鼠软肝化纤丸3.0、1.5 g;/(kg·d),另设空白对照组,连续给药26周,给药结束及停药4周后测血液生化、脏器系数及观察病理组织学变化.[结果] 26周及停药4周3.0 g/( kg·d)组和1.5 g/( kg·d)组实验大鼠血液生化指标、脏器系数指标与对照组相比,组间未见显著差异和异常改变,也未见毒理学意义变化和延迟性毒性反应.[结论]软肝化纤丸对血液生化指标、脏器的长期毒性较低,未发现毒性靶器官,可安全地应用于临床.     

塞隆骨对大鼠骨质疏松症治疗作用的研究

目的 :通过塞隆骨对大鼠骨质疏松症作用的研究 ,探讨塞隆骨治疗骨质疏松症的可能性。方法 :给大鼠饲喂低钙饲料 ,饮用去离子水 ,并注射地塞米松引起骨质疏松症 ,再灌胃塞隆骨治疗 5周 ,用骨矿物质含量分析仪测定骨密度 ,同时测定羟脯氨酸、骨灰分和骨钙含量 ,并进行骨组织形态学观察。结果 :塞隆骨和虎骨均可明显增加骨质疏松大鼠骨密度 ,尤其对髂骨密度、腰椎密度增加更明显 ,同时也可明显增加骨灰分和骨钙含量 ,另外对骨组织形态学异常也有明显改善作用 ,但对大鼠体重、血清钙和骨羟脯氨酸含量无明显影响。结论 :塞隆骨对骨质疏松模型大鼠的骨质疏松症状 ,具有较好的治疗作用。     

Antiimplantation mechanism of action of embelin in rats

The antiimplantation mechanism of action of embelin has been studied in rats. Its administration caused a significant reduction in ovarian and uterine wet weight. Ovarian histology revealed newly formed corpora lutea and the biochemical constituents were decreased. Similarly, the uterus of pregnant treated rats did not show any preparative changes, decidualization, apposition reaction, stimulation or proliferation. Biochemical constituents also behaved as those of cyclic rats even on the day of implantation. These findings suggest that the administration of embelin to pregnant rats keeps the ovary and uterus in a cyclic condition.     

白藜芦醇对阿霉素致心衰大鼠心肌损伤的保护作用

目的：观察白藜芦醇(resveratrol,RES)对阿霉素(adriamycin,ADR)致急性心衰大鼠心功能的保护作用。方法：取成年雄性SD大鼠30只,随机分为5组：空白对照组(NC),ADR模型组、RES低剂量(RES_L)+ADR组,RES高剂量(RES_H)+ADR组及RES组。RES_L+ADR,RES_H+ADR组及RES组,分别给予RES 30,120,120 mg·kg^-1·d^-1腹腔注射,1次/d,连续3 d；其他两组腹腔注射等量生理盐水。第4天除NC组及RES组外,其余3组一次性腹腔注射ADR10 mg·kg^-1,制备急性心衰大鼠模型。24 h后,光镜观察心肌细胞形态及生化指标的变化。结果：光镜观察显示,RES+ADR组心肌细胞的变性坏死明显减轻。ADR模型组丙二醛(MDA)、一氧化氮(NO)、一氧化氮合酶(NOS)显著增加,超氧化物岐化酶(SOD)显著减少(P<0.05)。与ADR模型组相比,RES_L+ADR,RES_H+ADR组的MDA,NO,NOS显著减少,SOD增加(P<0.05),并呈剂量依赖性。结论：RES可显著减轻ADR对心肌的毒性作用,其作用与抗氧化和减少NO的产生有关。