coq10和坎地沙坦对博莱霉素诱导大鼠肺纤维化的保护作用

Fatima Mohammad Saeed Mahdi, M. G. Alabbassi, Muthanna Ibrahim, Al-Ezzi
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引用次数: 3

摘要

肺纤维化是许多肺部疾病的最后阶段。其特点是基质产生过多,导致正常肺结构破坏,最终死亡。辅酶q10是膜氧化还原酶系统的重要组成部分。它是一种细胞内定位的抗氧化酶,在人体内内源性合成。辅酶q10保护细胞成分免受自由基诱导的氧化损伤的破坏。坎地沙坦是血管紧张素II型1受体(AT1)的选择性拮抗剂,广泛用于治疗高血压。最新研究表明血管紧张素II与循环器官组织的损伤和纤维化过程密切相关。目的:本动物研究旨在探讨Co Q10和坎地沙坦作为抗纤维化药物对肺纤维化的作用,重点关注与肺纤维化有关的选定标志物。材料与方法:48只大鼠随机分为4组,每组12只雄性大鼠。第一组:(对照组)经气管内注射生理盐水0.2 ml单次。第二组(BLM组),经气管内给药,给药剂量为8.3 U/kg。第三组(BLM+CoQ10组)大鼠给予BLM (8.3 U/kg)硫酸盐溶解于0.1 ml生理盐水中,气管内滴注,同时每天口服100mg /kg CoQ10,连续注射BLM前5天,注射后10天。IV组(BLM+坎地沙坦组)大鼠给予BLM (8.3 U/kg)硫酸盐溶解于0.1 ml生理盐水中,经气管内滴注,同时每日口服(10 mg/kg)坎地沙坦,连续注射BLM前5天、注射后10天。血清生物标志物为谷胱甘肽、花生四烯酸脂氧合酶,并进行三色染色组织病理学检查。结果:与对照组和(BLM+ CoQ10)相比,BLM组血清GSH浓度较低,但差异无统计学意义。与BLM组相比,(BLM+坎地沙坦)组血清GSH水平显著升高(P<0.05)。与对照组相比,BLM组血清ALOX5浓度显著升高(P < 0.05)。血清ALOX5水平(BLM+ CoQ10)极显著低于BLM组(P < 0.01), (BLM+坎地沙坦)组极显著低于BLM组(P < 0.001)。此外,组织学上,CoQ10和坎地沙坦显示炎症细胞数量减少,博来霉素引起的肺结构损伤和纤维化减少。结论:CoQ10和坎地沙坦可降低博来霉素诱导的雄性大鼠肺纤维化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protective Effect of Co Q10 and Candesartan on Bleomyycin Induced Lung Fibrosis in Rats
Fibrosis of the lungs is the final phase of many lung illnesses. Its characterized by excessive matrix production leading to the normal lung architecture destruction and eventually death. CoQ10 is an essential constituent of membrane oxidoreductase System. It is an intracellularly localized antioxidant   enzyme that is endogenously synthesized in humans. CoQ10 protects cellular components from destruction by free radical-induced oxidative damage. candesartan is a selective antagonist of angiotensin II type 1 receptor (AT1) and is widely employed for treatment of hypertension. Most up to date research shows angiotensin II close involvement with damage and fibrosis process in tissues of organs of circulation. Objective: This animal study was designed to investigate the effect of Co Q10 and candesartan as antifibrotic agents against pulmonary fibrosis focusing on selected markers involved in pulmonary fibrosis. Materials and Method: 48 rats divided randomly into four groups, each consisting of 12 male rats. Group I: (Control group), the rats in this group received single injection of 0.2 ml normal saline via intratracheal route. Group II: (The BLM group), received BLM (8.3 U/kg) as a single dose via the intratracheal rout. Group III: (BLM+CoQ10 group) rats receive BLM (8.3 U/kg) as sulfate salt dissolved in 0.1 ml of normal saline via the intratracheal instillation concomitant with 100 mg/kg co Q 10 per day orally for 5 days before and 10 days after BLM injection. Group IV: (BLM+ candesartan group) rats receive BLM (8.3 U/kg) as sulfate salt dissolved in 0.1 ml of normal saline via the intratracheal instillation concomitant with (10 mg/kg) candesartan per day orally for 5 days before and 10 days after BLM injection. The studied serum biomarkers were glutathione, arachidonate 5 lipoxygenase in addition to histopathological examination using trichrome stain.  Results: serum GSH concentration was lower in BLM group in comparison with the control group and the (BLM+ CoQ10) but this difference is not statistically significant. The serum GSH levels showed a significant(P<0.05) elevation in (BLM+ Candesartan) group when compared with the levels in the BLM group. The serum ALOX5 concentration was significantly elevated in BLM group in comparison with the control group (P < 0.05). The serum ALOX5 levels were highly significantly lower in (BLM +CoQ10) (P < 0.01) and very highly significantly lower in the (BLM+ Candesartan) group (P < 0.001) when comparing it with the levels in the BLM group. furthermore, histologically CoQ10 and candesartan showed reduction in the numbers of inflammation cells and a decrease in the damage to the lung architecture and fibrosis induced by bleomycin. Conclusion: CoQ10 and candesartan decrease pulmonary fibrosis induced by bleomycin in male rats.
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