Prourokinase combined with non-invasive delayed limb ischemic preconditioning in rat models of myocardial ischemia/reperfusion injury

doi:10.3969/j.issn.2095-4344.1332

Abstract

Abstract:

BACKGROUND: Prourokinase has been shown to hold good thrombolysis, and improve reperfusion injury after acute myocardial infarction. Non-invasive delayed limb ischemic preconditioning is a protective reaction after repeated transient ischemic preconditioning.
OBJECTIVE: To analyze the effect of prourokinase combined with non-invasive delayed limb ischemic preconditioning on myocardial ischemia/reperfusion injury in rats.
METHODS: The study was approved by the Experimental Animal Ethics Committee of Zhengzhou University, approval number: 1811034. Forty Sprague-Dawley rats were randomly divided into model, prourokinase, non-invasive delayed limb ischemic preconditioning and combined groups (n=10/group). Before modeling, non-invasive delayed limb ischemic preconditioning and combined groups were given non-invasive delayed limb ischemic preconditioning preconditioning for 3 days, and prourokinase and combined groups were given intravenous injection of prourokinase. Myocardial ischemia/reperfusion injury models were prepared by surgical ligation. Before and after modeling, the levels of creatine kinase-isozyme, lactic dehydrogenase, plasminogen activator inhibitor-1 and tissue plasminogen activator in serum were detected. After modeling, hematoxylin-eosin staining was used to detect myocardial tissue damage. The levels of tumor necrosis factor-α, interleukin-6, superoxide dismutase and malondialdehyde in myocardial tissue were detected by kit. The expression levels of tyrosine kinase JAK2, p-JAK2, signal transducers and activators of transcription 3 (STAT3), p-STAT3, Caspase-3, Bax and Bcl-2 were detected by western blot assay.
RESULTS AND CONCLUSION: (1) Compared with the model group, myocardial infarct size was significantly decreased in the prourokinase, non-invasive delayed limb ischemic preconditioning and combined groups (P < 0.05), and the myocardial infarct size in the combined group was significantly lower than that in the other groups (P < 0.05). (2) Compared with the model group, the levels of creatine kinase-isozyme, lactic dehydrogenase, tumor necrosis factor-α, interleukin-6 and malondialdehyde and plasminogen activator inhibitor-1 activity in the other three groups were significantly decreased (P < 0.05), especially in the combined group (P < 0.05). (3) Compared with the model group, the activities of tissue plasminogen activator and superoxide dismutase in the other three groups were significantly increased (P < 0.05), especially in the combined group (P < 0.05). (4) Compared with the model group, the apoptosis rate of myocardial tissue in the other three groups was significantly decreased (P < 0.05). The expression levels of Caspase-3 and Bax in myocardial tissue were significantly down-regulated (P < 0.05), especially in the combined group (P < 0.05). (5) The expression levels of Bcl-2, p-JAK2 and p-STAT3 in the other three groups were up-regulated significantly than in the model group (P < 0.05), especially in the combined group (P < 0.05). (6) These results suggest that prourokinase combined with non-invasive delayed limb ischemic preconditioning can improve myocardial ischemia/reperfusion injury and dysfunction, which may be related to JAK2/STAT3 signal pathway.

Key words: myocardial ischemia/reperfusion, prourokinase, non-invasive delayed limb ischemic preconditioning, JAK2/STAT3, malondialdehyde, superoxide dismutase

CLC Number:

Liu Zhiyuan, Zhang Jinying, Liu Jiangbo, Zhao Xiaoning, Liu Fei, Li Gang. Prourokinase combined with non-invasive delayed limb ischemic preconditioning in rat models of myocardial ischemia/reperfusion injury [J]. Chinese Journal of Tissue Engineering Research, 2019, 23(35): 5626-5632.

Figures/Tables 7

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