目的 研究碘塞羅寧對(duì)缺血性腦卒中的治療作用及機(jī)制。方法 線栓法制備小鼠大腦中動(dòng)脈閉塞(MCAO)模型,假手術(shù)組不插入線栓,對(duì)照組選用正常小鼠,模型小鼠分為模型組和碘塞羅寧低、中和高劑量(20、40、60 μg·kg^-1)組,在造模開始前6 d及造模結(jié)束后1 d,連續(xù)7 d每天1次尾iv給藥。造模結(jié)束后48 h,使用TTC法測(cè)定腦梗死體積;激光多普勒血流儀檢測(cè)局部腦血流(rCBF);ELISA法檢測(cè)血清血栓素B₂(TXB₂)、6酮前列腺素F1a (6-keto-PGF1a)、腫瘤壞死因子-α(TNF-α)和白細(xì)胞介素-6(IL-6)水平;Western blotting法檢測(cè)腦組織腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF)、SRY-box轉(zhuǎn)錄因子2(Sox2)和神經(jīng)巢蛋白(nestin)蛋白表達(dá)水平。結(jié)果 與模型組比較,碘塞羅寧高、中、低劑量組腦梗死體積均顯著減小(P<0.05、0.01),rCBF均顯著升高(P<0.05、0.01);碘塞羅寧高、中劑量組血清TXB2水平顯著降低(P<0.01),高劑量組血清6-keto-PGF1a水平顯著升高(P<0.05);碘塞羅寧各劑量組血清TNF-α和IL-6水平均顯著下降(P<0.05、0.01);碘塞羅寧高、中、低劑量組BDNF、nestin和Sox2的蛋白表達(dá)顯著增加(P<0.05、0.01)。結(jié)論 碘塞羅寧顯著改善缺血性腦卒中大鼠腦梗死,作用機(jī)制可能與抑制炎癥反應(yīng)、促進(jìn)血管舒張、促進(jìn)BDNF和神經(jīng)再生標(biāo)記物表達(dá)相關(guān)。

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.

R965

嘉峪關(guān)市科技計(jì)劃資助項(xiàng)目(19-35)