摘要
目的 探讨玄参提取物对脑缺血再灌注损伤(CRI)小鼠氧化应激及炎症反应的影响.方法 将60只SPF级雄性C57BL/6小鼠按随机数字表法分为模型组、正常组、阳性对照组、低剂量组和高剂量组,每组各12只.模型组、阳性对照组、低剂量组和高剂量组建立小鼠CRI模型.建模前,低、高剂量组小鼠术前分别给予5、20mL/kg玄参提取物灌胃;阳性对照组给予20 mL/kg辛伐他汀灌胃;模型组和正常组术前分别给予等量0.9%氯化钠注射液灌胃,均1次/d,连续5 d.采用Bederson评分法和Longa评分法评价小鼠神经功能;采用Morris水迷宫实验测定小鼠找到平台的时间(潜伏期)和穿越平台次数;采用硫代巴比妥酸比色法测定血清丙二醛(MDA)水平,采用黄嘌呤氧化酶法测定血清超氧化歧化酶(SOD)水平;采用ELISA法测定血清IL-6、IL-8和TNF-α水平;测量小鼠脑梗死体积百分比.结果 与正常组比较,其他各组Bederson评分、Longa评分、MDA水平、IL-6、IL-8和TNF-α水平、脑梗死体积百分比均明显增高,而SOD水平明显降低(均P<0.05);与模型组比较,阳性对照组、低剂量组与高剂量组Bederson评分、Longa评分、MDA水平、IL-6、IL-8和TNF-α水平、脑梗死体积百分比均明显降低,而SOD水平明显增高(均P<0.05);与阳性对照组和低剂量组比较,高剂量组Bederson评分、Longa评分、脑梗死体积百分比、MDA水平、IL-6、IL-8和TNF-α水平均明显降低,而SOD水平明显增高(均P<0.05).其他各组第1、2、3、4天潜伏期均长于正常组(均P<0.05);阳性对照组、低剂量组与高剂量组第1、2、3、4天潜伏期均短于模型组(均P<0.05);高剂量组第1、2、3、4天潜伏期均短于阳性对照组和低剂量组(均P<0.05).结论 玄参提取物对脑缺血再灌注损伤小鼠有较好的保护作用,可显著改善小鼠神经功能,明显缩小小鼠脑梗死体积,其机制可能与改善氧化应激及减轻炎症反应有关.
Abstract
Objective To explore effects of scrophulariae extract on oxidative stress and inflammatory response of mice with cerebral ischemia-reperfusion injury(CRI).Methods Sixty SPF grade male C57BL/6 mice were divided into model group,normal group,positive control group,low-dose group,and high-dose group using a random number table method,with 12 mice in each group.The mouse CRI models were established for the model group,positive control group,low-dose group and high-dose group.Before modeling,mice in the low and high dose groups were given 5 mL/kg and 20 mL/kg of scrophulariae extract by gavage before surgery,respectively;the positive control group was given 20 mL/kg of simvastatin by gavage;the model group and the normal group were both given an equal amount of 0.9%sodium chloride injection by gavage before surgery,both once a day,for five consecutive days.The mouse neurological function was evaluated using the Bederson and Longa scoring methods;the Morris water maze experiment was used to determine the time for mice to find the platform(incubation period)and the number of times they crossed the platform;serum malondialdehyde(MDA)levels were measured using thiobarbituric acid colorimetric method,and serum superoxide dismutase(SOD)levels were measured using xanthine oxidase method;enzyme linked immunosorbent assay was used to measure the levels of serum IL-6,IL-8,and TNF-α;the volume of cerebral infarction of mice was also measured.Results Compared with the normal group,the Bederson score,Longa score,MDA,IL-6,IL-8 and TNF-α levels,and percentage of cerebral infarction volume in other groups were significantly increased,while SOD levels were significantly reduced(all P<0.05);compared with the model group,the positive control group,low-dose group,and high-dose group showed significant reductions in Bederson score,Longa score,MDA,IL-6,IL-8 and TNF-α levels,as well as the percentage of cerebral infarction volume,while the SOD level increased significantly(all P<0.05);compared with the positive control group and the low-dose group,the high-dose group showed a significant decrease in Bederson score,Longa score,stroke volume percentage,MDA,IL-6,IL-8 and TNF-αlevels,while the SOD level increased significantly(all P<0.05).Compared with the normal group,the incubation periods on the 1,2,3 and 4 days in other groups were longer(all P<0.05);the incubation periods on days 1,2,3 and 4 in the positive control group,low-dose group,and high-dose group were shorter than those of the model group(all P<0.05);the incubation period of the high-dose group on days 1,2,3 and 4 were shorter than that of the positive control group and the low-dose group(all P<0.05).Conclusion Scrophulariae extract has a good protective effect on mice with CRI,significantly improving their neurological function and reducing the volume of cerebral infarction.Its mechanism may be related to reducing oxidative stress and inflammatory response.