软坚消瘿颗粒长期毒性对大鼠脏器影响的研究

发布时间：2018-04-30 13:37

本文选题：软坚消瘿颗粒 + 长期毒性　；参考：《辽宁中医药大学》2014年硕士论文

【摘要】：目的：本课题属于中药复方软坚消瘿颗粒的长期毒性研究，基于前期药学实验探明软坚消瘿颗粒的制备工艺、质量标准及稳定性、急性毒性和药效学基础上，进一步判断动物长期服用软坚消瘿颗粒是否发生毒性反应，描述毒性反应的性质和程度（包括毒性起始时间、程度、持续时间以及可逆性等）和靶器官，确定安全范围，并探讨毒性作用机制。本文重点对大鼠脑、肝、心、脾、肺、肾等主要脏器的组织病理学进行研究探讨。材料与方法： 1.实验材料根据研究需求，实验动物采用SPF级，体重为120±20g的SD品系大鼠240只，雌雄两性各半。动物合格证号(SCXKI辽SO10-001)。所有动物均符合国家有关药物非临床安全性研究的要求。受试药物是中药复方软坚消瘿颗粒（柴胡、当归、莪术、陈皮、浙贝母、海藻、昆布、赤芍，共8味中药）。本次药品由辽宁中医药大学附属医院中医药实验中心制剂室提供。 2.实验方法将240只大鼠在正式开始实验前于辽宁中医药大学附属医院中医药实验中心的动物实验室（温度18-23℃、湿度40%～60%）适应性常规饲养1周。将大鼠按照体重、性别分层随机分配。分为软坚消瘿颗粒低、中、高三个剂量组和生理盐水对照组，每组60只，雌雄各半。每周按所称体重计算给药量。正常对照组生理盐水1.5ml/100g2次/日；软坚消瘿颗粒低剂量组8g生药/kg/d（1.51g粉末/kg/d）（1.5ml/100g5%2次/日）；软坚消瘿颗粒中剂量组20g生药/kg/d（3.77g粉末/kg/d）（1.5ml/100g12.56%2次/日）；软坚消瘿颗粒高剂量组60g生药/kg/d（11.32g粉末/kg/d）（1.5ml/100g37.68%2次/日）；对照组给予1.5ml/100g生理盐水灌胃。每日灌胃2次，每周给药6天，周日停止给药，连续给药6个月。恢复期为2周。在给药3个月后（中期）、六个月后（末期）、和六个半月后（恢复期）分别随机抽取1/3数量大鼠给予25%乌拉坦腹腔注射麻醉，进行取血。取血后对大鼠进行系统尸解，对脏器进行称重并计算脏器系数后做组织病理学检查。结果： 1.软坚消瘿颗粒长期毒性试验过程中，各组大鼠外观皮毛、行为活动、精神状态等未见明显异常，口、鼻、眼、耳等腺体未见有异样分泌物。但软坚消瘿颗粒低、中、高剂量组大鼠粪便多呈褐色，其颜色与软坚消瘿颗粒冲剂相近，考虑为药物本身颜色所致，非毒性引起。 2.软坚消瘿颗粒长期给药对大鼠摄食量有影响，其中低、中、高剂量组与生理盐水对照组对比，结果见表1-1和表1-2，在不同时间阶段可出现P＜0.05的情况，有统计学意义。但研究者认为主要影响大鼠摄食量的原因是药物刺激胃肠消化吸收并占据了部分胃空间。 3.软坚消瘿颗粒长期毒性试验中，每周所称体重，低、中、高剂量组与生理盐水对照组对比，结果见表2-1和表2-2。不同时间阶段，出现P＜0.05的情况，有统计学意义。但研究者认为多与摄食量关系密切，非毒性所致。 4.软坚消瘿颗粒长期给药对大鼠脏器系数有影响，，在中期、末期、恢复期三个阶段，其低、中、高剂量组与生理盐水对照组对比，部分脏器系数P＜0.05，有统计学意义，但是否为软坚消瘿颗粒长期毒性所致有待进一步的研究。 5.组织病理学检查显示，大鼠低、中、高、剂量组与生理盐水对照组相比，其主要脏器镜下结构未见明显异常。结论： 1.软坚消瘿颗粒长期服用对大鼠的一般情况无明显影响。 2.软坚消瘿颗粒长期服用对大鼠日常摄食量有一定影响，但非毒性引起。 3.软坚消瘿颗粒长期服用对大鼠体重有一定影响，但非毒性引起。 4.软坚消瘿颗粒长期服用对大鼠脑、肝、心、脾、肺、肾等器官的脏器系数略有影响，但多数恢复期可逆。 5.软坚消瘿颗粒在长期毒性试验中，组织病理学检查未见异常。 6.软坚消瘿颗粒长期用药是基本安全的。
[Abstract]:Objective : To study the long - term toxicity of Chinese traditional Chinese medicine compound soft solid Xiaoying granules . Based on the preparation technology , quality standard and stability , acute toxicity and pharmacodynamics of soft solid Xiaoying granules , the characteristics and extent of toxicity reaction ( including initiation time , degree , duration , reversibility , etc . ) and target organs were further determined , the safety range was determined , and the mechanism of toxic action was discussed . This paper mainly studied the histopathological study of the brain , liver , heart , spleen , lung , kidney and other organs of rats .

Materials and Methods :

1 . Experimental material

According to the research requirements , 240 male and female male and female male and female male and female male and female , 240 male and female male and female male and female male and female were used in the experimental animals . All the animals were in compliance with the requirements of the national drug non - clinical safety study . The tested drugs were Chinese traditional Chinese medicine compound soft solid Xiaoying granules ( Radix Bupleuri , Radix Angelicae Sinensis , Curcumae Rhizoma , Pericarpium Citri Tangerinae , Bulbus Fritillariae Thunbergii , seaweed , kelp , Radix Paeoniae Rubra , and 8 Chinese medicines ) . The medicine is provided by the laboratories of the Central Pharmaceutical Experimental Center of the Affiliated Hospital of Chinese Medical University of Liaoning .

2 . Test Method

The rats were randomly divided into three dosage groups : soft masses , medium , high three dose groups and normal saline control group .
8 g of crude drug / kg / day ( 1.5ml / 100g5 % 2 times per day ) in low - dose group .
20 g crude drug / kg / day ( 3.77 g powder / kg / d ) ( 1.5ml / 100g12 . 56 % 2 times per day ) in the dosage group of soft extract gall granules ;
60 g / kg / day ( 11.32g powder / kg / d ) ( 1.5ml / 100g37.68 % 2 times per day ) .
The control group was given 1.5 ml / 100 g of physiological saline to fill the stomach . The rats were administered twice daily , 6 days a week , dosing on Sunday , 6 months after continuous administration . After 3 months of administration ( mid - term ) , 6 months later ( end ) , and six months later ( recovery period ) , 1 / 3 of rats were randomly selected to inject 25 % uranotan into the abdominal cavity for anesthesia and blood taking . After taking the blood , the rats were subjected to systemic necropsy , the organs were weighed and the organ coefficients were calculated for histopathological examination .

Results :

1 . During the long - term toxicity test , the appearance fur , behavioral activity and mental state of the rats in each group were not obviously abnormal . There were no abnormal secretion in the glands , such as mouth , nose , eye and ear .

2 . The effect of long - term administration on the feeding amount in rats was shown in Table 1 - 1 and Table 1 - 2 . The results were shown in Table 1 - 1 and Table 1 - 2 .

3 . In the long - term toxicity test , the weight , low , medium and high dosage groups were compared with normal saline control group , and the results were shown in Table 2 - 1 and Table 2 - 2 . The results showed that P & lt ; 0.05 had statistical significance in different time periods . However , the researchers thought that there was close relationship between dietary intake and non - toxicity .

4 . The effect of long - term administration on organ coefficients in rats was studied . In the middle , middle and high dose groups , there was a significant difference between the low and middle and high dose groups compared with normal saline control group .

5 . The histopathological examination showed that the lower , medium , and high dose groups of the rats showed no obvious abnormality in the structure of the main organ under the main organ mirror compared with the normal saline control group .

Conclusion :

1 . There was no obvious effect on the general situation of the rats in long - term administration .

2 . The long - term administration of soft - jian Xiaoying granules had some effects on the daily intake of rats , but it was not caused by toxicity .

3 . The long - term administration of soft - jian Xiaoying granules had some effects on the weight of rats , but it was not caused by toxicity .

4 . The long - term administration of soft - jian Xiaoying granules has a slight effect on the organ coefficients of organs such as brain , liver , heart , spleen , lung and kidney , but most of the recovery periods are reversible .

5 . In the long - term toxicity test , the histopathological examination showed no abnormality .

6 . The long - term use of soft - solid Xiaoying granules is basically safe .

【学位授予单位】：辽宁中医药大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R285.5

【参考文献】