PDF(Pubmed)
Abstract：
We assessed whether allicin, through its antihypertensive and antioxidant effects, relieves vascular remodeling, endothelial function, and oxidative stress (OS), thereby improving experimental pulmonary arterial hypertension (PAH). Allicin (16 mg/kg) was administered to rats with PAH (monocrotaline 60 mg/kg). Allicin encouraged body weight gain and survival rate, and medial wall thickness and the right ventricle (RV) hypertrophy were prevented. Also, angiotensin II concentrations in the lung (0.37 ± 0.01 vs. 0.47 ± 0.06 pmoles/mL, allicin and control, respectively) and plasma (0.57 ± 0.05 vs. 0.75 ± 0.064, allicin and control respectively) and the expressions of angiotensin-converting enzyme II and angiotensin II type 1 receptor in lung tissue were maintained at normal control levels with allicin. In PAH rats treated with allicin, nitric oxide (NO) (31.72 ± 1.22 and 51.4 ± 3.45 pmoles/mL), tetrahydrobiopterin (8.43 ± 0.33 and 10.14 ± 0.70 pmoles/mL), cyclic guanosine monophosphate (5.54 ± 0.42 and 5.64 ± 0.73 pmoles/mL), and Ang-(1-7) (0.88 ± 0.23 and 0.83 ± 0.056 pmoles/mL) concentrations increased in lung tissue and plasma, respectively. In contrast, dihydrobiopterin increase was prevented in both lung tissue and plasma (5.75 ± 0.3 and 5.64 ± 0.73 pmoles/mL); meanwhile, phosphodiesterase-5 was maintained at normal levels in lung tissue. OS in PAH was prevented with allicin through the increased expression of Nrf2 in the lung. Allicin prevented the lung response to hypoxia, preventing the overexpression of HIF-1α and VEGF. Allicin attenuated the vascular remodeling and RV hypertrophy in PAH through its effects on NO-dependent vasodilation, modulation of RAS, and amelioration of OS. Also, these effects could be associated with the modulation of HIF-1α and improved lung oxygenation. The global effects of allicin contribute to preventing endothelial dysfunction, remodeling of the pulmonary arteries, and RV hypertrophy, preventing heart failure, thus favoring survival. Although human studies are needed, the data suggest that, alone or in combination therapy, allicin may be an alternative in treating PAH if we consider that, similarly to current treatments, it improves lung vasodilation and increase survival. Allicin may be considered an option when there is a lack of efficacy, and where drug intolerance is observed, to enhance the efficacy of drugs, or when more than one pathogenic mechanism must be addressed.
摘要：
我们评估了大蒜素，通过其降压和抗氧化作用，缓解血管重塑,内皮功能，和氧化应激(OS)，从而改善实验性肺动脉高压(PAH)。将大蒜素(16mg/kg)给予具有PAH(野百合碱60mg/kg)的大鼠。大蒜素促进体重增加和存活率，并防止了内侧壁厚度和右心室（RV）肥大。此外，肺中血管紧张素II浓度（0.37±0.01vs.0.47±0.06pmoles/mL，大蒜素和对照，分别）和血浆（0.57±0.05vs.0.75±0.064，大蒜素和对照），肺组织中血管紧张素转换酶II和血管紧张素II1型受体的表达用大蒜素维持在正常对照水平。在用大蒜素治疗的PAH大鼠中，一氧化氮（NO）（31.72±1.22和51.4±3.45pmoles/mL），四氢生物蝶呤（8.43±0.33和10.14±0.70pmoles/mL），环磷酸鸟苷（5.54±0.42和5.64±0.73pmoles/mL），肺组织和血浆中Ang-（1-7）（0.88±0.23和0.83±0.056pmoles/mL）浓度增加，分别。相比之下,双氢生物蝶呤在肺组织和血浆中的增加都得到了阻止（5.75±0.3和5.64±0.73pmoles/mL）；同时，肺组织中磷酸二酯酶-5维持在正常水平。大蒜素通过增加Nrf2在肺中的表达来预防PAH中的OS。大蒜素阻止了肺部对缺氧的反应，防止HIF-1α和VEGF的过度表达。大蒜素通过其对NO依赖性血管舒张的作用减弱PAH中的血管重塑和RV肥大，RAS的调制，和操作系统的改进。此外，这些作用可能与调节HIF-1α和改善肺氧合有关。大蒜素的整体作用有助于预防内皮功能障碍，肺动脉的重塑，和RV肥大,预防心力衰竭,从而有利于生存。虽然需要进行人体研究,数据表明，单独或联合治疗，如果我们考虑到，大蒜素可能是治疗PAH的一种替代方法，类似于目前的治疗方法，它改善肺血管舒张和增加生存率。当缺乏疗效时，大蒜素可能被认为是一种选择，在观察到药物不耐受的地方，为了增强药物的功效，或者当必须解决一种以上的致病机制时。
