芪蝎活血通络汤对局灶性脑缺血再灌注损伤模型大鼠神经功能、氧化应激及炎症因子的影响

Effects of Qixie Huoxue Tongluo Decoction on Nerve Function,Oxidative Stress and Inflammatory Factors in Rats with Focal Cerebral Ischemia-Reperfusion Injury

目的:探讨芪蝎活血通络汤对局灶性脑缺血再灌注损伤模型大鼠神经功能、氧化应激及炎症因子的影响。方法:50只SD大鼠随机选取40只采用线栓法构建脑缺血再灌注模型,其中36只成功,4只死亡。随机数字表法将36只脑缺血再灌注模型大鼠分为模型组、低剂量组(芪蝎活血通络汤2.0 mg/kg灌胃处理)、中剂量组(芪蝎活血通络汤4.0 mg/kg灌胃处理)和高剂量组(芪蝎活血通络汤8.0 mg/kg灌胃处理),每组9只,剩余10只大鼠仅切开皮肤分离和夹闭血管(对照组)。建模后芪蝎活血通络汤各剂量组给予相应剂量灌胃,对照组和模型组给予同剂量生理盐水灌胃,持续4周。用药4周后测评各组大鼠神经功能缺损程度、双侧贴纸去除时间、平衡木过杆时间,并测定各组大鼠脑组织中含水量、脑梗死面积以及氧化应激[过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)]和炎症因子[白细胞介素-1β(IL-1β),白细胞介素-6(IL-6),肿瘤坏死因子-α(TNF-α)]指标。结果:与对照组比较,模型组大鼠m NSS评分、脑组织含水量、MDA含量、IL-6、IL-1β、TNF-α水平升高(P<0.05),双侧贴纸去除时间、平衡木过杆时间延长(P<0.05),脑梗死面积增大(P<0.05),SOD、GSH-Px、CAT活性降低(P<0.05);与模型组比较,芪蝎活血通络汤各剂量组大鼠m NSS评分、脑组织含水量、MDA含量、IL-6、IL-1β、TNF-α水平降低(P<0.05),双侧贴纸去除时间、平衡木过杆时间缩短(P<0.05),脑梗死面积缩小(P<0.05),SOD、GSH-Px、CAT活性升高(P<0.05);与低剂量组比较,中、高剂量组大鼠m NSS评分降低(P<0.05),双侧贴纸去除时间、平衡木过杆时间缩短(P<0.05);高剂量组大鼠脑梗死面积、脑组织MDA、IL-6、IL-1β、TNF-α低于低剂量组(P<0.05),SOD、GSH-Px、CAT高于低剂量组(P<0.05)。结论:芪蝎活血通络汤可降低大鼠脑缺血再灌注损伤,改善神经功能,其治疗作用可能与抗氧化,抗炎作用有关,8.0 mg/kg剂量效果最显著。

Objective: To investigate the effects of Qixie Huoxue Tongluo decoction on nerve function, oxidative stress and inflammatory factors in rats with focal cerebral ischemia-reperfusion injury. Methods: 40 SD rats were randomly selected from 50 SD rats to construct a cerebral ischemia reperfusion model by wire bolt method, among which 36 rats were successful, and 4 died. 36 rats of cerebral ischemia reperfusion model were divided into model group, low dose group(Qixie Huoxue Tongluo decoction 2.0 mg/kg lavage treatment), medium dose group(Qixie Huoxue Tongluo decoction 4.0 mg/kg lavage treatment) and high dose group(Qixie Huoxue Tongluo decoction 8.0 mg/kg lavage treatment) by random number table method, with 9 rats in each group, the remaining 10 rats were separated and clipped by skin incision only(control group). After modeling, each dose group of Qixie Huoxue Tongluo decoction was given corresponding dose by gavage, and the control group and the model group were intragastric with normal saline of the same volume,for 4 weeks. 4 weeks after treatment, the degree of neurological impairment, double side sticker removal time, the balance beam bar time of each group were measured. Brain tissue water content, cerebral infarct volume, oxidative stress [superoxide dismutase(SOD),glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA)] and inflammatory factors [interleukin-1β(IL-1β),interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)] indexes in each group rats were measured. Results: Compared with control group,m NSS score, the brain tissue water content, MDA content, IL-6, IL-1β, TNF-α levels in model group were increased(P<0.05), the double side sticker removal time, the balance beam bar time were prolonged(P<0.05), cerebral infarction volume was increased(P<0.05), SOD,GSH-Px and CAT activity were decreased(P<0.05). Compared with model group, m NSS score, the brain tissue water content, MDA content, IL-6, IL-1β, TNF-α levels in each dose group of Qixie Huoxue Tongluo decoction were decreased(P<0.05), the double side sticker removal time, the balance beam bar time were shortened(P<0.05), cerebral infarction volume was reduced(P<0.05), SOD,GSH-Px and CAT activity were increased(P<0.05). Compared with the low dose group, the m NSS score of the medium and high dose groups were decreased(P<0.05), the double side sticker removal time, the balance beam bar time were shortened(P<0.05). The cerebral infarction area, MDA, IL-6, IL-1β, TNF-α in the high dose group were lower than those in the low dose group(P<0.05), while SOD,GSH-Px and CAT in the high dose group were higher than those in the low dose group(P<0.05). Conclusion: Qixie Huoxue Tongluo decoction can reduce cerebral ischemia-reperfusion injury, and improve nerve function in rats, and its therapeutic effect may be related to antioxidant and anti-inflammatory effects. The 8.0 mg/kg dose has the most significant effect.