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从毒液中分离得到的金属蛋白酶 BmooMPα-I 可降低血压、逆转肾血管性高血压大鼠的左心室重构并改善心脏电传导。

BmooMPα-I, a Metalloproteinase Isolated from Venom, Reduces Blood Pressure, Reverses Left Ventricular Remodeling and Improves Cardiac Electrical Conduction in Rats with Renovascular Hypertension.

机构信息

Laboratory of Pharmacology and Toxicology of Cardiovascular System, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, PA, Brazil.

Laboratory of Hemostasis and Venoms, Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.

出版信息

Toxins (Basel). 2022 Nov 5;14(11):766. doi: 10.3390/toxins14110766.

Abstract

BmooMPα-I has kininogenase activity, cleaving kininogen releasing bradykinin and can hydrolyze angiotensin I at post-proline and aspartic acid positions, generating an inactive peptide. We evaluated the antihypertensive activity of BmooMPα-I in a model of two-kidney, one-clip (2K1C). Wistar rats were divided into groups: Sham, who underwent sham surgery, and 2K1C, who suffered stenosis of the right renal artery. In the second week of hypertension, we started treatment (Vehicle, BmooMPα-I and Losartan) for two weeks. We performed an electrocardiogram and blood and heart collection in the fourth week of hypertension. The 2K1C BmooMPα-I showed a reduction in blood pressure (systolic pressure: 131 ± 2 mmHg; diastolic pressure: 84 ± 2 mmHg versus 174 ± 3 mmHg; 97 ± 4 mmHg, 2K1C Vehicle, < 0.05), improvement in electrocardiographic parameters (Heart Rate: 297 ± 4 bpm; QRS: 42 ± 0.1 ms; QT: 92 ± 1 ms versus 332 ± 6 bpm; 48 ± 0.2 ms; 122 ± 1 ms, 2K1C Vehicle, < 0.05), without changing the hematological profile (platelets: 758 ± 67; leukocytes: 3980 ± 326 versus 758 ± 75; 4400 ± 800, 2K1C Vehicle, > 0.05), with reversal of hypertrophy (left ventricular area: 12.1 ± 0.3; left ventricle wall thickness: 2.5 ± 0.2; septum wall thickness: 2.3 ± 0.06 versus 10.5 ± 0.3; 2.7 ± 0.2; 2.5 ± 0.04, 2K1C Vehicle, < 0.05) and fibrosis (3.9 ± 0.2 versus 7.4 ± 0.7, 2K1C Vehicle, < 0.05). We concluded that BmooMPα-I improved blood pressure levels and cardiac remodeling, having a cardioprotective effect.

摘要

BmooMPα-I 具有激肽原酶活性,可裂解激肽原释放缓激肽,并能在脯氨酸和天冬氨酸位置水解血管紧张素 I,生成无活性肽。我们在双肾一夹(2K1C)模型中评估了 BmooMPα-I 的降压活性。Wistar 大鼠分为 Sham 组(接受假手术)和 2K1C 组(右肾动脉狭窄)。在高血压的第二周,我们开始进行为期两周的治疗(Vehicle、BmooMPα-I 和 Losartan)。在高血压的第四周,我们进行了心电图检查和血液及心脏采集。2K1C BmooMPα-I 显示血压降低(收缩压:131 ± 2mmHg;舒张压:84 ± 2mmHg 与 174 ± 3mmHg;97 ± 4mmHg,2K1C Vehicle,<0.05),心电图参数改善(心率:297 ± 4bpm;QRS:42 ± 0.1ms;QT:92 ± 1ms 与 332 ± 6bpm;48 ± 0.2ms;122 ± 1ms,2K1C Vehicle,<0.05),而血液学特征无变化(血小板:758 ± 67;白细胞:3980 ± 326 与 758 ± 75;4400 ± 800,2K1C Vehicle,>0.05),左心室肥厚逆转(左心室面积:12.1 ± 0.3;左心室壁厚度:2.5 ± 0.2;室间隔壁厚度:2.3 ± 0.06 与 10.5 ± 0.3;2.7 ± 0.2;2.5 ± 0.04,2K1C Vehicle,<0.05)和纤维化(3.9 ± 0.2 与 7.4 ± 0.7,2K1C Vehicle,<0.05)。我们得出结论,BmooMPα-I 改善了血压水平和心脏重构,具有心脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bdb/9697896/8bd181ce7ea6/toxins-14-00766-g001.jpg

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