Effect of pyroptosis pathway nuclear factor κB/cysteine aspartic acid specific protease-1 on myocardial vulnerability after renal ischemia reperfusion in diabetic rats with Dexmedetomidine
1.The Third Clinical School, Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China;
2.Department of Anesthesiology, Cancer Hospital Affiliated to Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China
Abstract Objective To investigate the role of nuclear factor κB (NF-κB)/ cysteine aspartic acid specific protease-1 (caspase-1) in Dexmedetomidine (Dex) in alleviating myocardial vulnerability after renal ischemia reperfusion in diabetic rats. Methods Thirty SPF male Wistar rats aged 8-12 weeks, weighing 200-300 g, were fed with high fat for four weeks and intraperitoneal injection of 1% Streptozotocin (30 mg/kg) was used to establish a diabetes model. The animals were divided into control group, model group, and Dex group with eight animals in each group. Renal ischemia reperfusion model was established in the model group and the Dex group, while the control group was laparotomy only. Dex was injected into the tail vein at a rate of 2 μg/(kg·h) from 30 min before ischemia to 4 h after reperfusion in the left kidney in the Dex group, and the same amount of normal saline was injected into the model group and the control group simultaneously. At the end of the experiment, the myocardial and serum samples of the three groups were collected, and serum cardiac troponin I (cTnI), interleukin (IL)-1β, IL-18, IL-17a, IL-10, and tumor necrosis factor-α (TNF-α) levels were determined by enzyme- linked immunosorbent assay, and the apoptosis rate of cardiomyocytes was determined by TUNEL staining. The expressions of NF-κB p65, p-NF-κB p65, caspase-1, and GSDMD-N in myocardial tissues of the three groups were determined by Western blot. Results The levels of IL-1β, IL-18, cTnI, TNF-α, IL-17a, p-NF-κB, caspase-1, GSDMD-N, and apoptosis rate of cardiomyocytes in model group were higher than those in control group, and the levels of IL-10 were lower than those in control group (P＜0.05). The levels of IL-1β, IL-18, cTnI, TNF-α, IL-17a, p-NF-κB, caspase-1, GSDMD-N, and apoptosis rate of cardiomyocytes in Dex group were lower than those in model group, and the levels of IL-10 were higher than those in model group (P＜0.05). Conclusion Dex can reduce myocardial injury after renal ischemia-reperfusion in diabetic rats, improve cardiac function, and reduce the release of inflammatory factors, the mechanism of which may be related to inhibiting the expression of myocardial pyrogenic protein.
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