本文選題：-羥基- + -四甲基哌啶基-N-氧化物��； 參考：《中國(guó)藥學(xué)雜志》2017年18期

【摘要】：目的研究4-羥基-2,2,6,6-四甲基哌啶基-N-氧化物(tempol)對(duì)高原缺氧小鼠心肌組織的保護(hù)作用及機(jī)制。方法將110只小鼠隨機(jī)分為正常對(duì)照組、缺氧模型組、乙酰唑胺組和tempol組,單次腹腔注射給藥30 min后,在模擬海拔8 000 m環(huán)境停留12 h,眼眶取血后,測(cè)定血清中乳酸脫氫酶(LDH)和肌酸激酶(CK)活性,然后處死小鼠,檢測(cè)心肌組織中過氧化氫(H_2O_2)和丙二醛(MDA)含量以及ATP酶和抗氧化酶的活性,蛋白印跡法檢測(cè)缺氧誘導(dǎo)因子-1α(HIF-1α)、血管內(nèi)皮生長(zhǎng)因子(VEGF)、核因子E2相關(guān)因子2(Nrf2)和血紅素氧合酶-1(HO-1)蛋白的表達(dá)水平。結(jié)果與正常對(duì)照組相比,缺氧模型組血清中CK和LDH的活性顯著增加,心肌組織中H_2O_2和MDA含量顯著升高,ATP酶和抗氧化酶的活性顯著降低,HIF-1α、VEGF、Nrf2和HO-1蛋白表達(dá)增強(qiáng)。經(jīng)tempol預(yù)處理后能夠顯著降低高原缺氧小鼠血清中CK和LDH的活性,減少心肌組織中H_2O_2和MDA含量,提高ATP酶和抗氧化酶的活性,降低HIF-1α、VEGF蛋白表達(dá),顯著提高Nrf2和HO-1蛋白表達(dá)。結(jié)論 Tempol對(duì)高原缺氧誘導(dǎo)的心肌組織損傷具有保護(hù)作用,該作用與改善能量代謝,清除自由基,激活Nrf2/HO-1信號(hào)途徑,提高抗氧化酶活性,降低機(jī)體氧化應(yīng)激有關(guān)。
[Abstract]:Objective to study the protective effect and mechanism of 4-hydroxy-2-dimethylidene 6-tetramethylpiperidine (6-tetramethylpiperidinyl) on myocardial tissue of mice exposed to hypoxia at high altitude. Methods 110 mice were randomly divided into three groups: normal control group, hypoxia model group, acetazolamide group and tempol group. After 30 min of single intraperitoneal injection, the mice stayed at a simulated altitude of 8 000 m for 12 hours. The activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were measured. Then the mice were killed. The contents of H _ 2O _ 2) and malondialdehyde (MDA) in myocardial tissue and the activities of ATP and antioxidant enzymes were measured. The expression levels of hypoxia inducible factor-1 偽 (HIF-1 偽), vascular endothelial growth factor (VEGFN), nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein were detected by Western blot. Results compared with the normal control group, the activities of CK and LDH in serum of hypoxic model group were significantly increased, and the contents of H_2O_2 and MDA in myocardial tissue were significantly increased. The activities of ATPase and antioxidant enzymes were significantly decreased in hypoxic model group. The expression of HIF-1 偽 -VEGFNrf2 and HO-1 protein was significantly decreased in hypoxic model group. Pretreatment with tempol could significantly decrease the activities of CK and LDH in serum, decrease the contents of H_2O_2 and MDA in myocardium, increase the activities of ATP and antioxidant enzymes, decrease the expression of HIF-1 偽 -VEGF-protein, and increase the expression of Nrf2 and HO-1 protein. Conclusion Tempol has protective effect on myocardial tissue injury induced by hypoxia at high altitude, which is related to improving energy metabolism, scavenging free radicals, activating Nrf2/HO-1 signaling pathway, increasing antioxidant enzyme activity and reducing oxidative stress.
【作者單位】： 蘭州總醫(yī)院藥劑科全軍高原環(huán)境損傷防治重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(81202458) 全軍醫(yī)藥科研“十二五”面上項(xiàng)目資助(CLZ12JA04) 甘肅省自然科學(xué)基金資助項(xiàng)目(1308RJYA06) 中國(guó)博士后科學(xué)基金資助項(xiàng)目(2012M521926)
【分類號(hào)】：R965
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本文編號(hào)：1805388