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神经调节蛋白-1对脓毒症大鼠心肌损伤的作用研究

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目的 研究神经调节蛋白-1(NRG-1)抑制脓毒症大鼠心肌损伤及其作用机制。方法 采用盲肠结扎穿刺(CLP)法建立大鼠脓毒症模型,将SD大鼠分为假手术组、脓毒症组、脓毒症+NRG组[重组人NRG(rhNRG)10 μg/kg]。成功造模12、24 h后,取各组存活大鼠心脏及外周血清。苏木素-伊红(HE)染色观察心脏组织形态结构变化,ELISA方法检测血清中肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、超敏肌钙蛋白(cTn T)表达水平及心脏组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)表达水平,Western blot检测大鼠心肌组织磷酸化蛋白激酶B(p-Akt)、磷酸化糖原合酶激酶3β(p-GSK3β)、B细胞淋巴瘤/白血病-2(Bcl-2)蛋白、Bax蛋白表达水平。结果 造模12、24 h后,与假手术组比较,脓毒血症组血清中CK、CK-MB、cTn Ⅰ表达水平及心肌组织中TNF-α、IL-6及Bax蛋白表达水平均明显升高,心肌组织中p-Akt、p-GSK3β表达水平明显降低(P<0。05);造模12、24 h后,与脓毒症组比较,脓毒症+NRG组血清中CK、CK-MB、cTn Ⅰ表达水平及心肌组织中TNF-α、IL-6表达水平均明显降低;造模24 h后,与脓毒症组比较,脓毒症+NRG组心肌组织中Bax蛋白表达水平明显降低,p-Akt、p-GSK3β表达水平明显升高(P<0。05);病理结果显示,与假手术组比较,脓毒症组产生明显病变;与脓毒症组比较,脓毒症+NRG组病变减轻。结论 脓毒症心肌损伤时相关生物标志物表达水平发生改变,NRG-1可以通过通路Akt/GSK3β改善心功能,抑制相关促炎因子,减轻心肌损伤。
The study on the effect of neuregulin-1 on myocardial injury in septic rats
Objective To study the effect of neuromodulatory protein-1(NRG-1)in inhibiting sepsis induced myocardial injury and its mechanism.Methods The rat sepsis model was established by cecal ligation and puncture(CLP).SD rats were divided into the sham operation group,sepsis group,sepsis+NRG group(rhNRG,10 μg/kg).After 12,24 h of successful modeling,the heart and peripheral serum of the surviving rats in each group were taken respectively.The HE staining was used to observe the changes of cardiac tissue morphology and structure,and ELISA was used to detect the expression levels of creatine kinase(CK),crea-tine kinase MB isoenzyme(CK-MB),sensitive troponin Ⅰ(cTnⅠ)in serum,tumor necrosis factor-α(TNF-α)in cardiac tissue and IL-6 expression level;Western blot was used to detect the phosphorylation protein ki-nase B(p-Akt),phosphorylation glycogen synthase kinaseβ(p-GSK3β),B-cell lymphoma/leukemia-2(Bcl-2)and Bax protein expression in rat myocardial tissue.Results After 12,24 h of modeling,compared with the sham group,the expression levels of CK,CK-MB and cTnⅠ in serum,TNF-α,IL-6 and Bax protein in myocar-dial tissue in the sepsis group all were significantly increased(P<0.05),while the expression levels of p-Akt and p-GSK3β in myocardial tissue were significantly decreased(P<0.05).After 12,24 h of modeling,com-pared with the sepsis group,the expression levels of CK,CK-MB,cTn Ⅰ in the serum and the expression levels of TNF-α,IL-6 in the myocardial tissue of the sepsis+NRG group were significantly decreased;after 24 h of modeling,compared with the sepsis group,the expression level of Bax protein in myocardial tissue of the sep-sis+NRG group was decreased,while the p-Akt,p-GSK3β expression levels were increased(P<0.05).The pathological results showed that compared with the sham operation group,the sepsis group produced signifi-cant lesions;compared with the sepsis group,the lesions in the sepsis+NRG group were alleviated.Conclusion The expression levels of related biomarkers in septic myocardial injury have change.NRG-1 could improve the cardiac function through Akt/GSK3β pathway,inhibit the related proinflammatory factors and reduce the myocardial tissue damage.

sepsisneuregulin-1ratsmyocardial injurycalmodulin

徐超、黄荣、赵鸿雁、曹静

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新疆医科大学第一附属医院昌吉分院:重症医学科,新疆昌吉 831110

新疆医科大学第一附属医院昌吉分院:心理医学科,新疆昌吉 831110

脓毒症 神经调节蛋白-1 大鼠 心肌损伤 钙调控蛋白

新疆维吾尔自治区自然科学基金

2020D01A118

2024

重庆医学
重庆市卫生信息中心,重庆市医学会

重庆医学

CSTPCD
影响因子:1.797
ISSN:1671-8348
年,卷(期):2024.53(2)
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