Özbudak Ersan, Eraldemir Fatma Ceyla, Arıkan Ali Ahmet, Şahin Deniz, Maral Kır Hale, Kurt Tolga, Gülaştı Ömer Faruk, Yavuz Şadan
Department of Cardiovascular Surgery, Akademi Hospital, Kocaeli, Turkey.
Department of Biochemistry, Kocaeli University Medical Faculty, Kocaeli, Turkey.
Turk Gogus Kalp Damar Cerrahisi Derg. 2019 Oct 23;27(4):513-520. doi: 10.5606/tgkdc.dergisi.2019.18061. eCollection 2019 Oct.
This study aims to compare clopidogrel and rivaroxaban against ischemia-reperfusion injury after a long reperfusion time and to investigate its effects on various tissues.
A total of 40 Wistar rats were included in the study and were randomly divided into four groups (n=10 per group). Groups were defined as follows: control (Group 1), sham (Group 2), clopidogrel pre-treatment (Group 3), and rivaroxaban pre-treatment (Group 4). Ischemia (6 h) and reperfusion (8 h) were induced at the lower hind limb in Groups 2, 3, and 4. The ischemic muscle, heart, kidney, liver, and plasma tissues of the subjects were obtained to test for the oxidant (malondialdehyde) and antioxidants (glutathione, superoxide dismutase, and nitric oxide).
Malondialdehyde levels were significantly higher in the sham group, compared to the controls in all tissues. Clopidogrel and rivaroxaban pre-treatment significantly decreased malondialdehyde levels, compared to the heart, ischemic muscle, liver, and blood tissues of the sham group. Kidney malondialdehyde levels were reduced only by rivaroxaban. Group 4 had significantly decreased malondialdehyde levels, compared to Group 3 in ischemic muscle (p<0.010). The glutathione reduction, compared to sham group, in the kidney was only significant for Group 4 (p<0.050). With clopidogrel and rivaroxaban pretreatment, nitric oxide levels significantly decreased only in the heart tissue, compared to sham group (p<0.001 and p<0.050, respectively).
The study results suggest that rivaroxaban and clopidogrel are effective in reducing ischemia-reperfusion injury in the heart, ischemic muscle, liver, and blood. Rivaroxaban also protects the kidneys and is superior to clopidogrel in ischemic muscle protection.
本研究旨在比较氯吡格雷和利伐沙班对长时间再灌注后的缺血再灌注损伤的影响,并研究其对各种组织的作用。
本研究共纳入40只Wistar大鼠,随机分为四组(每组n = 10)。分组如下:对照组(第1组)、假手术组(第2组)、氯吡格雷预处理组(第3组)和利伐沙班预处理组(第4组)。第2、3和4组在大鼠后肢下部诱导缺血(6小时)和再灌注(8小时)。获取受试者的缺血肌肉、心脏、肾脏、肝脏和血浆组织,检测氧化剂(丙二醛)和抗氧化剂(谷胱甘肽、超氧化物歧化酶和一氧化氮)。
与所有组织中的对照组相比,假手术组的丙二醛水平显著更高。与假手术组的心脏、缺血肌肉、肝脏和血液组织相比,氯吡格雷和利伐沙班预处理显著降低了丙二醛水平。仅利伐沙班降低了肾脏丙二醛水平。与第3组相比,第4组缺血肌肉中的丙二醛水平显著降低(p<0.010)。与假手术组相比,仅第4组肾脏中的谷胱甘肽减少显著(p<0.050)。与假手术组相比,氯吡格雷和利伐沙班预处理后,仅心脏组织中的一氧化氮水平显著降低(分别为p<0.001和p<0.050)。
研究结果表明,利伐沙班和氯吡格雷可有效减轻心脏、缺血肌肉、肝脏和血液中的缺血再灌注损伤。利伐沙班还可保护肾脏,在缺血肌肉保护方面优于氯吡格雷。