基线等比增减设计法优选黄芪注射液联合灯盏细辛注射液抗大鼠脑缺血再灌注损伤的最佳配比
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篇名: 基线等比增减设计法优选黄芪注射液联合灯盏细辛注射液抗大鼠脑缺血再灌注损伤的最佳配比
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摘要: 目的:筛选黄芪注射液联合灯盏细辛注射液抗大鼠脑缺血再灌注损伤的最佳配比。方法:将雄性SD大鼠随机分为假手术组、模型组和给药组[采用基线等比增减设计法设置黄芪注射液-灯盏细辛注射液不同剂量配比组,分别为A(0 ∶ 10)、B(2 ∶ 8)、C(4 ∶ 6)、D(6 ∶ 4)、E(8 ∶ 2)、F(10 ∶ 0)组],每组8只。除假手术组外,其余各组大鼠均采用改良线栓法复制大脑中动脉闭塞再灌注损伤模型。各给药组大鼠于模型复制后即时腹腔注射相应药物1次,24 h后再同法给药1次(两种注射剂的给药间隔为30 min);假手术组和模型组大鼠均腹腔注射等体积生理盐水。再灌注48 h后,采用Longa评分法评价各组大鼠的神经功能缺损情况,记录神经功能损伤评分;采用比色法检测其血清丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性;采用TTC法检测其脑梗死情况,计算脑梗死率。采用金氏公式计算各给药组大鼠的增效指数(q)。结果:与假手术组比较,模型组大鼠神经功能缺损评分和血清MDA含量均显著升高,血清SOD活性显著降低(P<0.01);脑梗死区域明显增大,其脑梗死率显著升高(P<0.01)。与模型组比较,A、B、C、D、E组大鼠神经功能缺损评分和血清MDA含量均显著降低,且C组神经功能缺损评分显著低于A、F组,B、C、D、E组血清MDA含量均显著低于F组(P<0.05或P<0.01);A、B、C、D、E组大鼠血清SOD活性均显著增强,且C组显著高于F组(P<0.05或P<0.01);各给药组大鼠脑梗死区域均有不同程度的缩小,B、C、D、E组大鼠脑梗死率均显著降低,且C、D组显著低于F组,C组显著低于A组(P<0.05或P<0.01)。B、C、D、E组大鼠的q值分别为0.90、1.30、1.00、0.70(神经功能缺损评分)和0.79、1.27、0.98、0.82(脑梗死率)。结论:以不同比例配伍的黄芪注射液和灯盏细辛注射液均对脑缺血再灌注损伤模型大鼠具有一定的保护作用,可缓解其神经功能缺损,减轻其氧化应激,并缩小其脑梗死区域;两药联用的效果优于单用,且其最佳配比为4 ∶ 6。
ABSTRACT: OBJECTIVE: To screen the best proportion of Astragalus membranaceus injection combined with Erigeron breviscapus injection against cerebral ischemia-reperfusion injury in rats. METHODS: Male SD rats were randomly divided into sham operation group, model group and administration group [different A. membranaceus injection-E. breviscapus injection proportion groups, being A(0 ∶ 10), B(2 ∶ 8), C(4 ∶ 6), D(6 ∶ 4), E(8 ∶ 2), F(10 ∶ 0)groups, set by baseline geometric proportion increasing and decreasing design], with 8 rats in each group. Except for sham operation group, reperfusion injury model of middle cerebral artery occlusion were induced by modified suture method in rats. The each administration group was given relevant medicine intraperitoneally once immediately after inducing model, and then given again after 24 hours (medication interval between the two injections of 30 min). Constant volume of normal saline was given to rats in sham operation group and model group. Forty-eight hours after reperfusion, Longa scoring method was used to evaluate neurological impairment of rats, and neurological impairment score was recorded. Serum content of MDA and activity of SOD were measured by colorimetry assay. TTC assay was used to detect cerebral infraction, and cerebral infarction rate was calculated. Kim’s formula was used to calculate the synergistic index (q) of rats in administration groups. RESULTS: Compared with sham operation group, neurological impairment score and serum content of MDA were increased significantly in model group, while activity of SOD was decreased significantly (P<0.01). The area of cerebral infarction increased significantly, and the rate of cerebral infarction increased significantly (P<0.01). Compared with model group, neurological impairment scores and serum contents of MDA were decreased significantly in group A, B, C, D and E; neurological impairment score of group C was significantly lower than those of group A and F; serum contents of MDA in group B, C, D and E were significantly lower than that of group F (P<0.05 or P<0.01). Activities of SOD in group A, B, C, D and E were increased significantly, and group C was significantly higher than group F (P<0.05 or P<0.01). The cerebral infarction area of rats in each administration group was reduced to varying degrees. The cerebral infarction rates of rats in group B, C, D and E were significantly reduced, and group C and D were significantly lower than group F, while group C was significantly lower than group A (P<0.05 or P<0.01). The q values of group B, C, D and E were 0.90, 1.30, 1.00, 0.70 (neurological impairment score) and 0.79, 1.27, 0.98, 0.82 (cerebral infarction rate). CONCLUSIONS: Different ratios of A. membranaceus injection and E. breviscapus injection have certain protective effects on cerebral ischemia-reperfusion injury model rats, can relieve their neurological deficits, alleviate their oxidative stress and reduce their cerebral infarction areas. The effect of the combination of the two drugs is better than that of single use, and the optimum ratio is 4 ∶ 6.
期刊: 2019年第30卷第14期
作者: 田枫,李佶操,唐绍微,孙雨诗,林诗佳,张芳艳,谢兴亮,盛艳梅
AUTHORS: TIAN Feng,LI Jicao,TANG Shaowei,SUN Yushi,LIN Shijia,ZHANG Fangyan,XIE Xingliang,SHENG Yanmei
关键字: 黄芪注射液;灯盏细辛注射液;联用;脑缺血再灌注损伤;基线等比增减设计法;剂量配比
KEYWORDS: Astragalus membranaceus injection; Erigeron breviscapus injection; Combination; Cerebral ischemia-reperfusion injury; Baseline geometric proportion increasing and decreasing design; Dose proportion
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