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血管紧张素转换酶抑制剂可独立于缓激肽受体抑制剂降低高血糖状态下大鼠的氧化应激强度。

Angiotensin-converting enzyme inhibitors reduce oxidative stress intensity in hyperglicemic conditions in rats independently from bradykinin receptor inhibitors.

作者信息

Mikrut Kinga, Kupsz Justyna, Kozlik Jacek, Krauss Hanna, Pruszynska-Oszmałek Ewa, Gibas-Dorna Magdalena

机构信息

Kinga Mikrut, Department of Physiology, Poznan University of Medical Sciences, Swiecickiego St., 6, 60-781 Poznan, Poland,

出版信息

Croat Med J. 2016 Aug 31;57(4):371-80. doi: 10.3325/cmj.2016.57.371.

Abstract

AIM

To investigate whether endogenous bradykinin is involved in the antioxidant action of angiotensin-converting enzyme inhibitors (ACEIs) in acute hyperglycemia.

METHODS

Male Wistar rats were divided into the normoglycemic group (n=40) and the hyperglycemic group (n=40). Hyperglycemia was induced by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) dissolved in 0.1 mol/L citrate buffer (pH 4.5) 72 hours before sacrifice. The normoglycemic group received the same volume of citrate buffer. Each group was divided into five subgroups (n=8): control group, captopril group, captopril + bradykinin B1 and B2 receptor antagonists group, enalapril group, and enalapril + bradykinin B1 and B2 receptor antagonists group. Captopril, enalapril, B1 and B2 receptor antagonists, or 0.15 mol/L NaCl were given at 2 and 1 hour before sacrifice. Oxidative status was determined by measuring the concentration of malondialdehyde and H2O2, and the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).

RESULTS

In STZ-induced hyperglycemic rats ACEIs significantly reduced H2O2 concentration, while they significantly enhanced SOD and GPx activity. The hyperglycemic group treated simultaneously with ACEIs and bradykinin B1 and B2 receptor antagonists showed a significant decrease in H2O2 concentration compared to the control hyperglycemic group.

CONCLUSION

These results suggest the existence of the bradykinin -independent antioxidative effect of ACEIs in hyperglycemic conditions, which is not related to the bradykinin mediation and the structure of the drug molecule.

摘要

目的

研究内源性缓激肽是否参与血管紧张素转换酶抑制剂(ACEIs)在急性高血糖状态下的抗氧化作用。

方法

将雄性Wistar大鼠分为正常血糖组(n = 40)和高血糖组(n = 40)。在处死前72小时,通过腹腔注射一次溶解于0.1 mol/L柠檬酸盐缓冲液(pH 4.5)中的链脲佐菌素(STZ,65 mg/kg体重)诱导高血糖。正常血糖组注射相同体积的柠檬酸盐缓冲液。每组再分为五个亚组(n = 8):对照组、卡托普利组、卡托普利+缓激肽B1和B2受体拮抗剂组、依那普利组、依那普利+缓激肽B1和B2受体拮抗剂组。在处死前2小时和1小时给予卡托普利、依那普利、B1和B2受体拮抗剂或0.15 mol/L NaCl。通过测量丙二醛和H2O2的浓度以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性来确定氧化状态。

结果

在STZ诱导的高血糖大鼠中,ACEIs显著降低H2O2浓度,同时显著增强SOD和GPx活性。与对照高血糖组相比,同时给予ACEIs和缓激肽B1和B2受体拮抗剂治疗的高血糖组H2O2浓度显著降低。

结论

这些结果表明,在高血糖条件下,ACEIs存在不依赖缓激肽的抗氧化作用,这与缓激肽介导和药物分子结构无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78c/5048232/b27848312d8b/CroatMedJ_57_0371-F1.jpg

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