基于豚鼠主动全身过敏实验和大鼠脑缺血再灌注炎症反应比较灯盏花素注射液和合成灯盏乙素注射液的安全性和有效性

Comparison the safety and efficacy of Breviscapine Injection and Synthetic Scutellarin Injection based on active systemic anaphylaxis in Hartley guinea pigs and inflammatory response in cerebral ischemia-reperfusion rats

关键词:  灯盏花素注射液  合成灯盏乙素注射液  主动全身过敏实验  脑缺血再灌注  炎症

Key words:  Breviscapine Injection  Synthetic Scutellarin Injection  active systemic anaphylaxis  cerebral ischemia reperfusion  inflammation

摘要:

[目的] 比较盏花素注射液（BI）和合成灯盏乙素注射液（SSI）的安全性和抗炎疗效。[方法] 豚鼠主动全身过敏实验：将豚鼠随机分为阴性对照组（氯化钠注射液），阳性对照组（牛血清白蛋白），BI低（BI-L，5 mg/kg）、高（BI-H，20 mg/kg）剂量组，SSI低（SSI-L，5 mg/kg）、高（SSI-H，20 mg/kg）剂量组，隔日致敏1次，共3次，于末次致敏后第12天激发，观察豚鼠是否出现过敏反应症状；抗大鼠脑缺血再灌注炎症反应实验：制备SD大鼠大脑中动脉栓塞（MCAO）模型，分成假手术组、模型组、尼莫地平组（1 mg/kg）、BI-L（2.1 mg/kg）、BL-H（4.2 mg/kg）、SSI-L（2.1 mg/kg）、SSI-H（4.2 mg/kg）剂量组，分别在连续给药1、3、7、14 d后检测各组大鼠血清中肿瘤坏死因子-α（TNF-α）、细胞间黏附分子-1（ICAM-1）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和白细胞介素-10（IL-10）含量。[结果] 豚鼠主动全身过敏实验：BI-L组1只弱阳性，5只阳性；BL-H组3只阳性，3只强阳性；SSI-L组5只阳性，1只强阳性；SSI-H组1只阴性，1只弱阳性，4只阳性。抗大鼠脑缺血再灌注炎症反应实验：与模型组相比，给药1 d后，BI-L组脑梗死体积显著减小（P＜0.01），给药14 d后，尼莫地平组、BI-L组和SSI-H组脑梗死体积显著减小（P＜0.05或P＜0.01）。给药1 d后，TNF-α含量除SSI-H组，其他给药组均显著降低（P＜0.05或P＜0.01）；IL-6、IL-1β含量除SSI-L组，其他给药组均显著降低（P＜0.05或P＜0.01）。给药3 d后，IL-10含量除SSI-L组，其他给药组均显著增加（P＜0.05或P＜0.01）。给药14 d后，TNF-α、ICAM-1、IL-1β含量给药组均显著降低（P＜0.05或P＜0.01）；IL-6含量除BI-L组，其他给药组均显著降低（P＜0.05或P＜0.01）；IL-10含量除BI-L组，其他给药组均显著增加（P＜0.05或P＜0.01）。[结论] SSI高剂量组过敏反应发生率较低，其安全性更好；BI低剂量组起效更快，SSI高剂量组作用更加持久。

Abstract:

[Objective] To compare the safety and anti-inflammatory efficacy of Breviscapine Injection(BI) and Synthetic Scutellarin Injection(SSI). [Methods] Active Systemic Anaphylaxis test in Hartley guinea pigs. Hartley guinea pigs were randomly divided into negative control group(sodium chloride injection),positive control group(bovine serum albumin),BI low dose(5 mg/kg) group,BI high dose(20 mg/kg) group,SSI low dose(5 mg/kg) group and SSI high dose(20 mg/kg) group,and were sensitized once every other day for 3 times,and stimulated on the 12th day after the last sensitization. And the symptoms of allergic reaction were observed. Cerebral ischemia-reperfusion inflammation test in rats. The middle cerebral artery embolization(MCAO) model of SD rats was prepared and they were divided into sham operation group,model group,Nimodipine group(1 mg/kg),BI-L(2.1 mg/kg),BL-H(4.2 mg/kg),SSI-L(2.1 mg/kg),and SSI-H(4.2 mg/kg) dose groups. The serum levels of tumor necrosis factor-α(TNF-α),intercellular adhesion molecule-1(ICAM-1),interleukin-6(IL-6),interleukin-1β(IL-1β) and interleukin-10(IL-10) were detected after 1,3,7 and 14 days of continuous administration. [Results] Active Systemic Anaphylaxis,in BI(5 mg/kg) group,1 was weakly positive and 5 were positive. In BI(20 mg/kg) group,3 were positive and 3 were strongly positive. SSI(5 mg/kg) was positive in 5 animals and strongly positive in 1 animal. In SSI(20 mg/kg) group,4 were positive,1 was weakly positive and 1 was negative. Cerebral ischemia-reperfusion inflammation test,compared with model group,after 1 day of administration,the volume of cerebral infarction in BI-L group was significantly decreased(P<0.01),and after 14 days of administration,the volume of cerebral infarction in Nimodipine,BI-L and SSI-H groups was significantly decreased(P<0.05 or P<0.01). After 1 day of administration,TNF-α content was significantly decreased in all other administration groups except the SSI-H group(P<0.05 or P<0.01). The contents of IL-6 and IL-1β were significantly decreased in all treatment groups except SSI-L group(P<0.05 or P<0.01). After 3 days of administration,IL-10 content was significantly increased in all groups except SSI-L group(P<0.05 or P<0.01). After 14 days of administration,the contents of TNF-α,ICAM-1 and IL-1β in administration groups were significantly decreased(P<0.05 or P<0.01). IL-6 content was significantly decreased in other administration groups except BI-L group(P<0.05 or P<0.01). IL-10 content was significantly increased in other administration groups except BI-L group(P<0.05 or P<0.01). [Conclusion] Lower incidence of allergic reactions and better safety in the high dose group of SSI. The effect of low-dose breviscapine group was faster,while the effect of high-dose synthetic scutellarin group was longer.