摘要
目的探讨氧化苦参碱(OMT)对蛛网膜下腔出血(SAH)大鼠脑血管痉挛的作用及机制的研究。方法将200只雄性大鼠分成假手术组、SAH组、小剂量组和大剂量组,每组50只。采用枕大池二次注血法制作SAH大鼠模型,假手术组大鼠两次均注入等量生理盐水,其余三组在模型建立后分别给予1 ml的0.9%氯化钠注射液,60和120 mg/kg的OMT腹腔注射。在术后1、3、5、7和10 d每组分别处死10只大鼠,测量四组大鼠基底动脉血管直径,检测基底动脉内皮细胞核因子κB(NF-κB)、胞外信号调节激酶(ERK)1/2、p38丝裂原活化蛋白激酶(MAPK)、c-Jun氨基末端激酶(JNK)的蛋白相对表达量,以及基底动脉内皮细胞白细胞介素1β(IL-1β)、IL-6和肿瘤坏死因子α(TNF-α)的m RNA相对表达水平。结果术后3、5、7和10 d,四组大鼠基底动脉血管直径(F=11.897、28.957、14.785、8.381,P均<0.05),基底动脉内皮细胞NF-κB(F=17.289、65.602、43.881、26.998,P均<0.05)、ERK1/2(F=204.331、145.948、107.442、30.332,P均<0.05)、p38MAPK(F=84.908、116.677、83.735、28.338,P均<0.05)和JNK(F=26.809、83.419、56.465、27.756,P均<0.05)蛋白表达,以及基底动脉内皮细胞IL-1β(F=66.625、262.620、283.499、218.081,P均<0.05)、IL-6(F=38.580、170.657、136.253、58.068,P均<0.05)和TNF-α(F=31.290、361.661、101.109、23.940,P均<0.05)m RNA水平的比较,差异均有统计学意义(P均<0.05)。其中术后3、5、7和10 d时间点上,假手术组和大剂量组大鼠基底动脉血管直径均较SAH组显著增大(P均<0.05),而这两组的基底动脉内皮细胞NF-κB、ERK1/2、p38MAPK和JNK的蛋白表达,以及IL-1β、IL-6和TNF-α的m RNA表达均显著少于SAH组(P均<0.05)。但小剂量组的以上指标和SAH组比较差异均无统计学意义(P均>0.05)。结论 OMT可改善SAH大鼠脑血管痉挛,其机制可能与OMT抑制脑血管内皮细胞NF-κB、ERK1/2、p38MAPK和JNK等信号通路,降低大鼠基底动脉血管炎症反应有关。
Objective To investigate the effect of oxymatrine（OMT） on cerebral vasospasm in rats with subarachnoid hemorrhage（SAH） and its related mechanism. Methods Two hundred rats were randomly divided into the sham group, SAH group, low and high dose treatment groups with 50 rats in each group. The SAH rat model was established by two injections of the autogenous blood into the cisterna magna, and rats in the sham group were only injected with the same volume saline twice. After surgery, the other three groups were given an intraperitoneal injection of 1 ml 0.9% sodium chloride, 60 or 120 mg / kg OMT, respectively.Ten rats from each group were sacrificed at 1, 3, 5, 7 and 10 d. The diameter of basilar artery was measured and the expression levels of nuclear factor-kappa B（NF-κB）, extracellular signalregulated kinase（ERK） 1 / 2, p38 mitogen activated protein kinase（MAPK）, c-Jun N-terminal kinase（JNK）, interleukin-1beta（IL-1β）, IL-6 and tumor necrosis factor-alpha（TNF-α） m RNA in endothelial cells were detected. Results At day 3, 5, 7 and 10 after surgery, the significant differences were found in the diameter of basilar artery（F = 11.897, 28.957, 14.785, 8.381; all P〈0.05）, as well as the protein expression levels of NF-κB（F = 17.289, 65.602, 43.881, 26.998; all P〈0.05）, ERK1 / 2（F = 204.331, 145.948, 107.442, 30.332; all P〈0.05）, p38 MAPK（F =84.908, 116.677, 83.735, 28.338; all P〈0.05）, JNK（F = 26.809, 83.419, 56.465, 27.756; all P〈0.05）, and the m RNA expression levels of IL-1β（F = 66.625, 262.620, 283.499, 218.081; all P〈0.05）, IL-6（F = 38.580, 170.657, 136.253, 58.068; all P〈0.05） and TNF-α（F = 31.290,361.661, 101.109, 23.940; all P〈0.05） among all four groups. Compared with the SAH group,at 3, 5, 7 and 10 d, the diameter of basilar artery in the sham and high dose treatment groups were dilated obviously（all P〈0.05）, as well as protein expression levels of NF-κB, ERK1 / 2, p38 MAPK, JNK and m RNA expression levels of IL-1β, IL-6 and TNF-α were significantly decreased（all P〈0.05）. However, these effects in the low dose treatment group were not obvious（all P〈0.05）. Conclusions OMT could inhibit cerebral vasospasm of rats with SAH. It may reduce vascular inflammatory reaction of basilar artery via OMT-depressed NF-κB, ERK1 / 2, p38 MAPK and JNK signaling pathways in cerebrovascular endothelial cells.
作者
闻贤强
戴伟民
黄强
余国峰
严欣江
Wen Xianqiang Dai Weimin Huang Qiang Yu Guofeng Yan Xinjiang(Graduate School, Zhejiang Chinese Medical University, Hangzhou 310000, Chino Department of Neurosurgery, Quzhou People＇s Hospital, Quzhou 324000, China)
出处
《中华危重症医学杂志（电子版）》
CAS
2016年第5期321-327,共7页
Chinese Journal of Critical Care Medicine:Electronic Edition
基金
浙江省中医药科技计划项目(2014ZB132)
