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.
[1] Lam-Chung CE，Cuevas-Ramos D. The promising role of risk scoring system for Cushing syndrome：Time to reconsider current screening recommendations [J]. Front Endocrinol，2022，13：1075785.
[2] Peng K，McIlroy DR，Bollen BA，et al. Society of Cardiovascular Anesthesiologists Clinical Practice Update for Management of Acute Kidney Injury Associated With Cardiac Surgery [J]. Anesth Analg，2022，135（4）：744-756.
[3] Chen X，Hu J，Lai J，et al. Dexmedetomidine Attenuates LPS- Stimulated Alveolar Type Ⅱ Cells’Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway [J]. Can Respir J，2022，2022：8433960.
[4] Guo H，Zhang W，Wang Z，et al. Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage [J]. Front Mol Neurosci，2022，15：977941.
[5] Hermansen JL，Pettey G，S?覬rensen HT，et al. Perioperative Doppler measurements of renal perfusion are associated with acutekidney injury in patients undergoing cardiac surgery [J]. Sci Rep，2021，11（1）：19738.
[6] Zhang B，Zhang J，Ainiwaer Y，et al. Dexmedetomidine Attenuates Myocardial Injury Induced by Renal Ischemia/ Reperfusion by Inhibiting the HMGB1-TLR4-MyD88- NF-κB Signaling Pathway [J]. Ann Clin Lab Sci，2021，51（3）： 376-384.
[7] Wu Y，Zhang J，Yu S，et al. Cell pyroptosis in health and inflammatory diseases [J]. Cell Death Discov，2022，8（1）：191.
[8] Gong D，Wang L，Yang Y，et al. Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress，inflammation，and apoptosis [J]. Ren Fail，2019， 41（1）：750-761.
[9] Zou R，Nie C，Pan S，et al. Co-administration of hydrogen and metformin exerts cardioprotective effects by inhibiting pyroptosis and fibrosis in diabetic cardiomyopathy [J]. Free Radic Biol Med，2022，183（4）：35-50.
[10] 庞玉萍.绞股蓝总皂苷对2型糖尿病大鼠游离脂肪酸代谢的影响及改善胰岛素抵抗相关机制研究[J].中华中医药学刊，2016，34（4）：960-963.
[11] 李新灵，雷钟，杜靖，等.不同剂量右美托咪定对大鼠肾缺血再灌注后心肌组织损伤的影响[J].医学研究生学报，2015，28（8）：809-814.
[12] 吉芳，伊合山·艾尼瓦尔，张静静，等.NF-κB信号通路在大鼠肾缺血再灌注损伤致心肌损伤中的作用[J].新疆医科大学学报，2019，42（11）：1404-1408，1413.
[13] Pan Y，Cai W，Huang J，et al. Pyroptosis in development，inflammation and disease [J]. Front Immunol，2022，13：991044.
[14] Hou J，Hsu J，Hung M. Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity [J]. Mol Cell，2021，81（22）：4579-4590.
[15] Zhan X，Peng W，Wang Z，et al. Polysaccharides from Garlic Protect against Liver Injury in DSS-Induced Inflammatory Bowel Disease of Mice via Suppressing Pyroptosis and Oxidative Damage [J]. Oxid Med Cell Longev，2022，2022：2042163.
[16] Poznyak A，Grechko AV，Poggio P，et al. The Diabetes Mellitus-Atherosclerosis Connection：The Role of Lipid and Glucose Metabolism and Chronic Inflammation [J]. Int J Mol Sci，2020，21（5）：1835.
[17] Liu Y，Wang T，Zhang M，et al. Down-regulation of myocardial infarction associated transcript 1 improves myocardial ischemia-reperfusion injury in aged diabetic rats by inhibition of activation of NF-κB signaling pathway [J]. Chem Biol Interact，2019，30（25）：111-122.
[18] Chen Y，Zhou Y，Wang Q，et al. Conciliatory Anti-Allergic Decoction Attenuates Pyroptosis in RSV-Infected Asthmatic Mice and LPS-Induced 16HBE Cells by Inhibiting TLR3/ NLRP3/NF-κB/IRF3 Signaling Pathway [J]. J Immunol Res，2022，2022：1800401.
[19] Yu Z，Xiao Z，Guan L，et al. Translocation of gasdermin D induced mitochondrial injury and mitophagy mediated quality control in lipopolysaccharide related cardiomyocyte injury [J]. Clin Transl Med，2022，12（8）：e1002.
[20] Ye X，Zhang P，Zhang Y，et al. GSDMD contributes to myocardial reperfusion injury by regulating pyroptosis [J]. Front Immunol，2022，23（13）：893-914.
[21] Zheng Z，Wang T，Chen J，et al. Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis [J]. Front Immunol，2021，7（12）：674-688.
[22] Cao R，Li Z，Wu C，et al. Identification of a Small Molecule with Strong Anti-Inflammatory Activity in Experimental Autoimmune Encephalomyelitis and Sepsis through Blocking Gasdermin D Activation [J]. J Immunol，2022，209（4）：820- 828.
[23] Wang C，Yuan W，Hu A，et al. Dexmedetomidine alleviated sepsis-induced myocardial ferroptosis and septic heart injury [J]. Mol Med Rep，2020，22（1）：175-184.
[24] Wang L，Wang S，Jia T，et al. Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirt1 [J]. Bioengineered，2022，13（4）：9369- 9386.
[25] Wei B，Liu W，Jin L，et al. Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats [J]. Front Cell Neurosci，2022，16：899484.
京公网安备 11010502046598号