注射用丹参多酚酸对脑缺血再灌注大鼠脑损伤的保护作用

Protective effect of Salvianolic Acid for Injection on brain injury in rats with cerebral ischemia and reperfusion

目的考察注射用丹参多酚酸(SAFI)对脑缺血再灌注大鼠脑损伤的保护作用。方法线拴法构建大脑中动脉缺血再灌注(MCAO/R)大鼠模型,将造模成功的大鼠随机分为模型组、丁苯酞氯化钠注射液(阳性药,9 mL·kg^(−1))组和SAFI低、中、高剂量(5.85、11.71、23.42 mg·kg^(−1),11.71 mg·kg^(−1)为临床等效剂量)组,每组12只。假手术组和模型组给予0.9%氯化钠注射液,SAFI每天给药1次,丁苯酞氯化钠注射液每天给药2次,尾iv连续给药14 d。给药期间称大鼠体质量;给药前后对各组大鼠进行神经功能评分;给药后采用TTC染色法检测脑梗死体积;酶联免疫吸附(ELISA)法检测血清中γ干扰素(IFN-γ)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和超氧化物歧化酶(SOD)的水平;HE染色观察脑组织病理形态;尼氏染色观察海马区尼氏小体形态变化情况。结果给药14 d后,与模型组比较,SAFI 5.85、11.71、23.42 mg·kg^(−1)组和丁苯酞氯化钠注射液组大鼠体质量显著增加(P<0.001),脑组织梗死体积显著缩小(P<0.001);SAFI 11.71、23.42 mg·kg^(−1)组和丁苯酞氯化钠注射液组神经功能评分显著降低(P<0.05、0.01),IFN-γ、IL-1β和TNF-α水平均显著降低(P<0.01、0.001),SOD水平显著升高(P<0.01、0.001);SAFI 23.42 mg·kg^(−1)组和丁苯酞氯化钠注射液组IL-6水平显著降低(P<0.05、0.01);SAFI可明显改善MCAO/R大鼠脑组织缺血半暗带区病理损伤,抑制尼氏小体数的减少。结论SAFI对脑缺血再灌注大鼠脑损伤具有明显的保护作用。

Objective To investigate the protective effect of Salvianolic Acid for Injection(SAFI)on brain injury after cerebral ischemia reperfusion in rats.Methods The rat model of middle cerebral artery ischemia reperfusion(MCAO/R)was established by the method of tethering.The rats with successful modeling were randomly divided into model group,Butylphthalide Sodium Chloride Injection(BSCI,positive drug,9 mL·kg^(−1))group and SAFI low,medium and high dose(5.85,11.71,23.42 mg·kg^(−1),11.71 mg·kg^(−1)was the clinical equivalent dose)group,with 12 rats in each group.The sham-operation group and model group were given 0.9%sodium chloride injection,the SAFI group was given once a day,and the BSCI was given twice a day,and the tail iv was given continuously for 14 days.Weigh the weight of rats during administration.After 14 days,the changes of neurological function scores before and after administration were compared.The volume of cerebral infarction was detected by TTC staining.The contents of interferon-γ(IFN-γ),interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and superoxide dismutase(SOD)in serum were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological morphology of brain tissue.Morphological changes of Nissl bodies in hippocampus were observed by Nissl staining.Results After 14 days of administration,compared with model group,the body mass of rats in SAFI 5.85,11.71,23.42 mg·kg^(−1)group and BSCI group increased significantly(P<0.001),and the infarct volume of brain tissue decreased significantly(P<0.001).Compared with model group,SAFI 11.71,23.42 mg·kg^(−1)group and BSCI group had significantly lower neurological function scores(P<0.05,0.01),the level of SOD in serum was significantly increased,and the levels of INF-γ,IL-1β,IL-6 and TNF-ɑwere decreased(P<0.01,0.001).The level of IL-6 in SAFI 23.42 mg·kg^(−1)group and BSCI group decreased significantly compared with model group(P<0.05,0.01).SAFI could significantly improve the pathological damage of ischemic penumbra in MCAO/R rats and inhibit the reduction of Nissl corpuscles compared with model group.Conclusion SAFI has a significant protective effect on brain injury of cerebral ischemia-reperfusion rats.