1.新疆医科大学第六附属医院麻醉科,新疆 乌鲁木齐 830002
2.新疆昌吉市人民医院麻醉科,新疆 昌吉 831100
Received:05 August 2024,
Published:25 December 2025
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夏艳,王坤光,杜晓宣.右美托咪定改善心肌缺血/再灌注损伤及其诱导的急性肾损伤机制研究[J].局解手术学杂志,2025,34(12):1045-1050.
XIA Yan,WANG Kun-guang,DU Xiao-xuan.Mechanism of dexmedetomidine improves myocardial ischemia-reperfusion injury and its induced acute kidney injury[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(12):1045-1050.
夏艳,王坤光,杜晓宣.右美托咪定改善心肌缺血/再灌注损伤及其诱导的急性肾损伤机制研究[J].局解手术学杂志,2025,34(12):1045-1050. DOI: 10.11659/jjssx.08E024018.
XIA Yan,WANG Kun-guang,DU Xiao-xuan.Mechanism of dexmedetomidine improves myocardial ischemia-reperfusion injury and its induced acute kidney injury[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(12):1045-1050. DOI: 10.11659/jjssx.08E024018.
目的
2
探讨右美托咪定(DEX)对心肌缺血/再灌注(I/R)损伤及其诱导的急性肾损伤的影响及机制。
方法
2
建立SD大鼠心肌I/R损伤模型,将其分为假手术组(Sham组)、I/R组和DEX治疗组(I/R+DEX组)。超声心动图检测各组大鼠左室射血分数(EF)和短轴缩短率(FS),以评价心功能改变。ELISA法检测各组大鼠血清中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-4、IL-6、IL-17A、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、血肌酐(Scr)和血尿素氮(BUN)含量。TUNEL染色检测各组大鼠心肌组织和肾组织中的细胞凋亡水平。TTC染色检测各组大鼠心肌梗死面积。Western blot实验检测各组大鼠心肌组织和肾组织中核因子-κB(NF-κB)信号通路的p65磷酸化水平(p-p65/p65)和JAK/STAT信号通路中STAT3磷酸化(p-STAT3/STAT3)水平。
结果
2
与Sham组相比,I/R组和I/R+DEX组大鼠血清中TNF-α、IL-6、IL-17A、CK-MB、LDH、Scr和BUN含量均明显升高(
P
<
0.05),而IL-4、EF、FS均显著降低(
P
<
0.05);与I/R组相比,I/R+DEX组大鼠血清中TNF-α、IL-6、IL-17A、CK-MB、LDH、Scr及BUN含量均明显降低(
P
<
0.05),但IL-4、EF、FS均显著升高(
P
<
0.05)。与Sham组相比,I/R组和I/R+DEX组大鼠心肌梗死面积显著扩大(
P
<
0.01),心肌组织中B细胞淋巴瘤/白血病-2(Bcl-2)相关X蛋白(Bax)、裂解型半胱氨酸天冬氨酸蛋白酶-3(cleaved Caspase-3)表达升高(
P
<
0.05),Bcl-2蛋白表达显著降低(
P
<
0.05),心肌组织与肾组织中细胞凋亡率及p-p65/p65、p-STAT3/STAT3均显著升高(
P
<
0.05);与I/R组相比,I/R+DEX组中上述检测指标明显逆转(
P
<
0.05)。
结论
2
DEX可通过降低NF-κB和JAK/STAT信号通路的活性,来抑制炎症反应和细胞凋亡,以改善心肌I/R损伤及其诱导的肾损伤。
Objective
2
To investigate the effects and mechanisms of dexmedetomidine (DEX) on myocardial ischemia-reperfusion(I/R) injury and its induced acute kidney injury.
Methods
2
The myocardial I/R injury model of SD rats was established and divided into the Sham operation group (Sham group),the I/R group and the DEX treatment group (I/R+DEX group).Echocardiography was used to assess the changes in cardiac function by measuring left ventricular ejection fraction (EF) and fractional shortening (FS). ELISA was employed to determine the serum levels of tumor necrosis factor-α (TNF-α),interleukin(IL)-4,IL-6,and IL-17A,creatine kinase-MB (CK-MB),lactate dehydrogenase (LDH),serum creatinine (Scr),and blood urea nitrogen (BUN).TUNEL staining was used to assess the apoptosis in myocardial and renal tissues. TTC staining was used to measure myocardial infarction area. Western blot was conducted to detect the phosphorylation level of p65 in the nuclear factor-kappa B (NF-κB) signaling pathway (p-p65/p65) and the phosphorylation level of STAT3 in the JAK/STAT signaling pathway (p-STAT3/STAT3) in the myocardial and renal tissues of rats in each group.
Results
2
Compared with the Sham group,the I/R and I/R+DEX groups showed significantly increased serum levels of TNF-α,IL-6,IL-17A,CK-MB,LDH,Scr and BUN(
P
<
0.05),and decreased levels of IL-4,EF and FS (
P
<
0.05). Compared with the I/R group,the I/R+DEX group had significantly lower serum levels of TNF-α,IL-6,IL-17A,CK-MB,LDH,Scr and BUN(
P
<
0.05),and higher levels of IL-4,EF and FS (
P
<
0.05). Compared with the Sham group,the myocardial infarction areas of rats in the I/R group and the I/R+DEX group were significantly expanded (
P
<
0.01),the expressions of B-cell leukemia/lymphoma 2(Bcl-2) associated X protein(Bax) and cleaved cysteinyl aspartate-specific protease-3(cleaved Caspase-3) in myocardial tissue were increased(
P
<
0.05),and the expressions of Bcl-2 protein were significantly decreased (
P
<
0.05),the apoptosis rates and the values of p-P65/p65 and p-S
TAT3/STAT3 in myocardial tissue and renal tissue were significantly increased (
P
<
0.05). Compared with the I/R group,the above-mentioned detection indicators in the I/R+DEX group were significantly reversed (
P
<
0.05).
Conclusion
2
DEX can inhibit inflammatory responses and apoptosis by reducing the activity of NF-κB and JAK/STAT signaling pathways,thereby improving myocardial I/R injury and the renal injury induced by myocardial I/R injury.
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