[关键词]
[摘要]
目的 研究5种活血化瘀类中药注射剂对大鼠局灶性脑缺血损伤的保护作用。方法 制备大鼠暂时性左侧中动脉栓塞(middle cerebral artery occlusion,tMCAO)模型,造模成功后实验动物随机分成7组,分别为模型组、注射用丹参多酚酸(11.71 mg/kg)组、注射用丹参多酚酸盐(17.86 mg/kg)组、银杏内酯注射液(0.91 mL/kg)组、银杏二萜内酯葡胺注射液(0.45 mL/kg)组、注射用血塞通(冻干) (18.02 mg/kg)组和丁苯酞氯化钠注射液(阳性药,9 mL/kg)组。假手术组同法造模,不栓塞大脑中动脉。各组大鼠尾iv给药14 d后,评估神经功能评分;干湿比质量法测定脑含水量;TTC染色法评价脑梗死面积;伊文思蓝法测定血脑屏障通透性;酶联免疫吸附试剂盒检测组织匀浆中白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、γ-干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)水平;生化分析法测定丙二醛(MDA)、超氧化物歧化酶(SOD)活性;HE染色法检测组织病理学变化;末端标记法(TUNEL)观察神经细胞及神经元凋亡情况。结果 给药后,与模型组比较,各给药组神经功能评分均降低,其中注射用丹参多酚酸组和注射用丹参多酚酸盐组差异显著(P<0.01);各给药组脑含水量均不同程度的降低,除注射用血塞通(冻干)和丁苯酞氯化钠注射液组外,其他各给药组均差异显著(P<0.01);各给药组脑梗死面积均显著下降,差异有统计学意义(P<0.01);各给药组给药后伊文思蓝渗出量均有不同程度的降低,其中注射用丹参多酚酸、注射用丹参多酚酸盐、注射用血塞通(冻干)和丁苯酞氯化钠注射液组差异显著(P<0.05、0.01);各给药组IFN-γ、IL-1β、IL-6和TNF-α含量均显著降低,差异均有统计学意义(P<0.05、0.01);各给药组均能不同程度抑制SOD的降低,其中注射用丹参多酚酸和注射用银杏内酯注射液组差异有统计学意义(P<0.01);各给药组均能不同程度抑制MDA的升高,其中注射用丹参多酚酸、注射用丹参多酚酸盐和银杏内酯注射液组差异均有统计学意义(P<0.01); 5种中药注射剂均能在不同程度抑制脑组织神经细胞和神经元病理形态的改变以及神经细胞的凋亡。结论 5种活血化瘀类中药注射剂对MCAO大鼠的损伤均具有较好的保护作用,但其改善各指标的程度不同。
[Key word]
[Abstract]
Objective To study the protective effect of five traditional Chinese medicine injections for promoting blood circulation and removing blood stasis on focal cerebral ischemic injury in rats. Method Preparation the left side of the artery embolism in rats (Middle cerebral artery occlusion, MCAO). After successful modeling, the experimental animals were randomly divided into eight groups:model group, Salvianolic Acids for Injection (11.71 mg/kg) group, Salvianolate for Injection (17.86 mg/kg) group, Ginkgolide Injection (0.91 mL/kg) group, Ginkgo Diterpene Lactone Meglumine Injection (0.45 mL/kg) group, Xuesetong for Injection (freeze-dried, 18.02 mg/kg) group, and Butylphthalide Sodium Chloride for Injection (positive drug, 9 mL/kg) group. After 14 days of caudal vein administration, neurological function score was evaluated in each group. The moisture content of brain was determined by dry and wet specific gravity method. The area of cerebral infarction was evaluated by TTC staining. The blood-brain barrier permeability was determined by Evensland method. The levels of IL-6, IL-1, IFN- and TNF-α in tissue homogenizer were detected by ELISA kit. The activity of MDA and SOD was measured by biochemical analysis. HE staining was used to detect histopathological changes. Apoptosis of neuronal cells and neurons was observed by Tunel. Results After administration, compared with the model group, the neurological function scores of each administration group decreased, and there was significant difference between Salvianolic Acids for Injection and Salvianolate for injection group (P<0.01). Except Xuesetong for Injection (freezedried) group and Butylphthalide Sodium Chloride for Injection group, the brain water content of each treatment group decreased significantly (P<0.01). The area of cerebral infarction in each treatment group decreased significantly (P<0.01). Evans blue exudation decreased in different degrees in each treatment group, and there were significant differences in Salvianolic Acids for Injection group, Salvianolate for Injection group, Xuesetong for Injection (freeze-dried) group and Butylphthalide Sodium Chloride for Injection group (P<0.05, 0.01). The contents of IFN-γ, IL-1β, IL-6 and TNF-α in each administration group were significantly decreased (P<0.05, 0.01). Each administration group could inhibit the decrease of SOD in varying degrees, and there was significant difference between Salvianolic Acids for Injection group and Ginkgolide Injection group (P<0.01). Each administration group could inhibit the increase of MDA in varying degrees, and there were significant differences among Salvianolic Acids for Injection group, Salvianolate for Injection group and Ginkgolide Injection group (P<0.01). The five traditional Chinese medicine injections can inhibit the pathological changes of nerve cells and neurons and the apoptosis of nerve cells in brain tissue to varying degrees. Conclusion Five kinds traditional Chinese medicine injection of promoting blood circulation and removing blood stasis have good protective effect on the injury of MCAO rats. However, the degree of improvement of each index is different.
[中图分类号]
R285.5
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