[關(guān)鍵詞]
[摘要]
目的 研究5種活血化瘀類中藥注射劑對大鼠局灶性腦缺血損傷的保護作用。方法 制備大鼠暫時性左側(cè)中動脈栓塞(middle cerebral artery occlusion,tMCAO)模型,造模成功后實驗動物隨機分成7組,分別為模型組、注射用丹參多酚酸(11.71 mg/kg)組、注射用丹參多酚酸鹽(17.86 mg/kg)組、銀杏內(nèi)酯注射液(0.91 mL/kg)組、銀杏二萜內(nèi)酯葡胺注射液(0.45 mL/kg)組、注射用血塞通(凍干) (18.02 mg/kg)組和丁苯酞氯化鈉注射液(陽性藥,9 mL/kg)組。假手術(shù)組同法造模,不栓塞大腦中動脈。各組大鼠尾iv給藥14 d后,評估神經(jīng)功能評分;干濕比質(zhì)量法測定腦含水量;TTC染色法評價腦梗死面積;伊文思藍法測定血腦屏障通透性;酶聯(lián)免疫吸附試劑盒檢測組織勻漿中白細胞介素-6(IL-6)、白細胞介素-1β(IL-1β)、γ-干擾素(IFN-γ)、腫瘤壞死因子-α(TNF-α)水平;生化分析法測定丙二醛(MDA)、超氧化物歧化酶(SOD)活性;HE染色法檢測組織病理學(xué)變化;末端標(biāo)記法(TUNEL)觀察神經(jīng)細胞及神經(jīng)元凋亡情況。結(jié)果 給藥后,與模型組比較,各給藥組神經(jīng)功能評分均降低,其中注射用丹參多酚酸組和注射用丹參多酚酸鹽組差異顯著(P<0.01);各給藥組腦含水量均不同程度的降低,除注射用血塞通(凍干)和丁苯酞氯化鈉注射液組外,其他各給藥組均差異顯著(P<0.01);各給藥組腦梗死面積均顯著下降,差異有統(tǒng)計學(xué)意義(P<0.01);各給藥組給藥后伊文思藍滲出量均有不同程度的降低,其中注射用丹參多酚酸、注射用丹參多酚酸鹽、注射用血塞通(凍干)和丁苯酞氯化鈉注射液組差異顯著(P<0.05、0.01);各給藥組IFN-γ、IL-1β、IL-6和TNF-α含量均顯著降低,差異均有統(tǒng)計學(xué)意義(P<0.05、0.01);各給藥組均能不同程度抑制SOD的降低,其中注射用丹參多酚酸和注射用銀杏內(nèi)酯注射液組差異有統(tǒng)計學(xué)意義(P<0.01);各給藥組均能不同程度抑制MDA的升高,其中注射用丹參多酚酸、注射用丹參多酚酸鹽和銀杏內(nèi)酯注射液組差異均有統(tǒng)計學(xué)意義(P<0.01); 5種中藥注射劑均能在不同程度抑制腦組織神經(jīng)細胞和神經(jīng)元病理形態(tài)的改變以及神經(jīng)細胞的凋亡。結(jié)論 5種活血化瘀類中藥注射劑對MCAO大鼠的損傷均具有較好的保護作用,但其改善各指標(biāo)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.
[中圖分類號]
R285.5
[基金項目]