[关键词]
[摘要]
目的 研究碘塞罗宁对缺血性脑卒中的治疗作用及机制。方法 线栓法制备小鼠大脑中动脉闭塞(MCAO)模型,假手术组不插入线栓,对照组选用正常小鼠,模型小鼠分为模型组和碘塞罗宁低、中和高剂量(20、40、60 μg·kg-1)组,在造模开始前6 d及造模结束后1 d,连续7 d每天1次尾iv给药。造模结束后48 h,使用TTC法测定脑梗死体积;激光多普勒血流仪检测局部脑血流(rCBF);ELISA法检测血清血栓素B2(TXB2)、6酮前列腺素F1a (6-keto-PGF1a)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平;Western blotting法检测脑组织脑源性神经营养因子(BDNF)、SRY-box转录因子2(Sox2)和神经巢蛋白(nestin)蛋白表达水平。结果 与模型组比较,碘塞罗宁高、中、低剂量组脑梗死体积均显著减小(P<0.05、0.01),rCBF均显著升高(P<0.05、0.01);碘塞罗宁高、中剂量组血清TXB2水平显著降低(P<0.01),高剂量组血清6-keto-PGF1a水平显著升高(P<0.05);碘塞罗宁各剂量组血清TNF-α和IL-6水平均显著下降(P<0.05、0.01);碘塞罗宁高、中、低剂量组BDNF、nestin和Sox2的蛋白表达显著增加(P<0.05、0.01)。结论 碘塞罗宁显著改善缺血性脑卒中大鼠脑梗死,作用机制可能与抑制炎症反应、促进血管舒张、促进BDNF和神经再生标记物表达相关。
[Key word]
[Abstract]
Objective To study the therapeutic effect and mechanism of liothyronine on ischemic stroke. Method Line suppository preparation of middle cerebral artery occlusion (MCAO) model was made in mice, the control group was not insert line switch, control group choose normal mice, model mice was divided into model group, liothyronine low, middle and high dose (20, 40 and 60 μg·kg-1) group, six days before model and one day after model, one times daily for 7 d tail iv drug delivery. Totally 48 h after modeling, infarct volume was determined by TTC method. Local cerebral blood flow (rCBF) was detected by laser Doppler flow analyzer. Serum levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a (6-keto-PGF1a), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by ELISA. The expression levels of brain-derived neurotrophic factor (BDNF), SCL-Box transcription factor 2 (Sox2) and nestin protein in brain tissues were detected by Western blotting. Result Compared with model group, the infarct volume was significantly decreased (P<0.05, 0.01) and rCBF was significantly increased (P<0.05, 0.01) in liothyronine high, middle and low dose groups. The serum level of TXB2 in liothyronine high and middle groups was significantly decreased (P <0.01), and the serum level of 6-keto-PGF1a in liothyronine high-dose group was significantly increased (P<0.05). Serum TNF-α and IL-6 levels were significantly decreased in liothyronine groups (P<0.05, 0.01). The protein expressions of BDNF, nestin and Sox2 were significantly increased in liothyronine groups (P<0.05, 0.01). Conclusion Liothyronin significantly improved cerebral infarction in rats with ischemic stroke, and the mechanism may be related to inhibiting inflammatory response, promoting vasodilation, and promoting the expression of BDNF and nerve regeneration markers.
[中图分类号]
R965
[基金项目]
嘉峪关市科技计划资助项目(19-35)