醒脑静注射液对Beagle犬脑外伤昏迷治疗的量效关系
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1.中南大学湘雅二医院,长沙 410011; 2.湖南省药物安全评价研究中心 & 新药药效与安全性评价湖南省重点 实验室,长沙 410331; 3.湖南中医药大学,长沙 410208; 4.景德镇市第三人民医院,江西 景德镇 333000

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R-33

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Dose-effect relationship of xingnaojing injection on beagle dog coma treatment
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1.Xiangya Second Hospital of Central South University, Changsha 410011, China. 2. Hunan Center of Drug Safety Evaluation and Research of Drugs; Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410331. 3. Hunan University of Chinese Medicine, Changsha 410208. 4. Jingdezhen Third People’s Hospital, Jingdezhen 333000

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    摘要:

    目的 观察醒脑静注射液对Beagle犬昏迷治疗的量效关系的影响。 方法 雄性 Beagle犬42只,体重 8~ 10 kg,按体重随机分为正常对照组、模型对照组、醒脑静注射液剂量 1 组(0. 43 mL/ kg)、剂量 2 组(0. 86 mL/ kg)、剂量3双次给药组((0. 43+0. 43) mL/ kg)、剂量 4 组(1. 29 mL/ kg)、剂量5双次给药组((0. 65+0. 65) mL/ kg),犬采用陆眠宁(0. 02 mL/ kg)麻醉后固定在自制打击器中,将打击器置于 150 cm 处,垂直打击犬颅脑枕部,连续打击4次,建立犬外伤脑损伤昏迷模型。造模后随即给予不同剂量醒脑静注射液,给药体积10. 0 mL/ kg,观察苏 醒时间,随后进行脑部核磁共振检测,给药14 d后进行核磁共振检查,取血检测血常规及肝肾功能、血清S-100钙结合蛋白(S-100B)、神经元特异性烯醇化酶(NSE)含量。取各组动物心、肝、脾、肺、肾、肾上腺、脑进行组织病理学检查。 结果 醒脑静注射液剂量1、剂量2(单次给药)、剂量 3(2 次给药)能明显减少犬苏醒时间。醒脑静剂量 1、醒脑静剂量 2、醒脑静剂量4能明显降低血清S100B、NSE 含量。醒脑静剂量1、剂量2、剂量3(2次给药)、剂量 4、 剂量5(2次给药)能明显增加犬脑核磁共振检测损伤恢复面积(P<0. 05)。 醒脑静注射液剂量 1 组、2 能明显降低血常规淋巴细胞、嗜酸性粒细胞数目;醒脑静注射液剂量1能明显降低犬单核细胞数目;醒脑静注射液剂量4、5对犬血常规无明显影响。醒脑静注射液各给药组对肝肾功能指标(ALT、AST、TBil、BUN、CRE)无明显差异。各组动 物心、肝、脾、肺、肾、脑器官组织病理学未见明显差异。 结论 醒脑静注射液能明显改善 Beagle 犬脑外伤致昏迷和 脑损伤程度,且大剂量使用无明显的毒副作用。

    Abstract:

    Objective To observe the dose-effect relationship of xingnaojing injection in treating coma in beagle dogs. Methods Male beagles were divided into nine groups at random: Control, Model, Naloxone ( 0. 01 mg / kg),Xingnaojing group (dose 1) (0. 215 mL/ kg), Xingnaojing group (dose 2) (0. 43 mL/ kg), Xingnaojing group ( dose 3, single dose) ( 0. 86 mL/ kg), Xingnaojing group ( dose 3, double dose) (( 0. 43 + 0. 43) mL/ kg), Xingnaojing group (dose 4, single dose) ( 1. 29 mL/ kg), and Xingnaojing group ( dose 4, double dose) (( 0. 65 + 0. 65) mL/ kg). Lu mianning was used for anesthesia, fixed in a custom-made hammer, and a model of traumatic brain injury in dogs was established. MRI was performed, intravenous medication for 14 days. The waking time, coma degree, and cortical electroencephalogram were measured. After the last intravenous administration of medication, MRI was performed and blood was taken to determine liver and kidney function, along with routine blood tests and measurements of NSE and S-100B. Cerebrospinal fluid was used to measure Glu, GABA, and His. Histopathological examination was performed on the heart, liver, spleen, lung, kidney, adrenal gland, brain, pituitary, sciatic nerve, and spinal nerve from animals in each group, and some organs were weighed. Results Xingnaojing injection doses 1, 2 (single dose), and 3 (two doses) significantly reduced the waking time of dogs. Xingnaojing doses 1, 2, and 4 significantly reduced the levels of S100B and NSE in serum. Xingnaojing doses 1, 2, 3 (2 doses), 4, and 5 (2 doses) significantly increased the area of brain injury recovery in dogs. The numbers of lymphocytes and eosinophils in xingnaojing injection group 1 and group 2 significantly decreased. Xingnaojing injection dose 1 significantly reduced the number of mononuclear cells in dogs. Xingnaojing injection doses 4 and 5 had no significant effect on canine blood routine findings. There were no significant differences in ALT, AST, TBil, BUN, and CRE between the xingnaojing injection groups. Xingnaojing injection showed no significant difference in histopathology of canine heart, liver, spleen, lung, kidney, and brain. Conclusions Xingnaojing injection clearly ameliorated the coma caused by traumatic brain injury in beagle dogs, while having no clear toxic effects at a high dose.

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陈瑞奇,曾贵荣,石镇港,戚 麟,张妙红,袁湘中,徐永兴,王 平,张乐君,洪 剑.醒脑静注射液对Beagle犬脑外伤昏迷治疗的量效关系[J].中国比较医学杂志,2020,30(1):36~44.

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  • 收稿日期:2019-08-31
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  • 在线发布日期: 2020-08-19
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