作者：张小赏，童随阳，操传斌

单位：

441300湖北省随州市，湖北医药学院附属随州医院心血管内科 通信作者：操传斌，E-mail：caochuanbin001@163.com

Units：

Department of Cardiology, Suizhou Hospital of Hubei University of Medicine, Suizhou 441300, China Corresponding author: CAO Chuanbin, E-mail: caochuanbin001@163.com

关键词：

心肌再灌注损伤; 心肌缺血再灌注损伤; 紫苏醛; 炎症反应;

Keywords：

Myocardial reperfusion injury; Myocardial ischemic reperfusion injury; Perillaldehyde; Inflammatory response

CLC：

DOI：

10.12114/j.issn.1008-5971.2022.00.046

Funds：

湖北省科技计划项目（2020CFB179）；湖北医药学院自由探索基金项目（FDFR201905）

摘要：

背景急性心肌梗死后可以通过介入治疗开通罪犯血管以挽救濒死心肌,但罪犯血管开通后中性粒细胞浸润、内皮细胞功能障碍等会引发心肌缺血/再灌注(I/R)损伤,通过药物调动内源性保护机制是对抗心肌I/R损伤的重要策略。紫苏醛(PAH)具有很强的抗炎、抗真菌作用,但其对心肌I/R损伤的作用尚不明确。目的 探讨PAH对心肌I/R损伤大鼠心肌保护作用机制及其最佳剂量。方法 2020年6月至2021年6月,从32只SPF级成年雄性Sprague-Dawley大鼠中选取20只随机分为假手术组、I/R损伤组、PAH18+I/R损伤组、PAH36+I/R损伤组、PAH72+I/R损伤组,每组4只。假手术组、I/R损伤组给予0.5%羧基纤维素连续灌胃1周,PAH18+I/R损伤组、PAH36+I/R损伤组、PAH72+I/R损伤组分别给予18、36、72 mg/kg的PAH连续灌胃1周,之后I/R损伤组、PAH18+I/R损伤组、PAH36+I/R损伤组、PAH72+I/R损伤组建立心肌I/R损伤模型;假手术组做相同的手术,但只穿线不结扎。比较五组大鼠血清心肌肌钙蛋白I(cTnI)、肌酸激酶(CK)、乳酸脱氢酶(LDH)水平及心肌损伤评分。将剩余的12只大鼠随机分为假手术组、I/R损伤组、PAH36+I/R损伤组,每组4只,干预方法同上;比较三组大鼠血浆肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、白介素(IL)-6水平。结果 I/R损伤组、PAH18+I/R损伤组、PAH36+I/R损伤组、PAH72+I/R损伤组大鼠血清cTnI、CK、LDH水平高于假手术组(P<0.05);PAH36+I/R损伤组、PAH72+I/R损伤组大鼠血清cTnI水平低于I/R损伤组,PAH18+I/R损伤组、PAH36+I/R损伤组、PAH72+I/R损伤组大鼠血清CK、LDH水平低于I/R损伤组(P<0.05);PAH36+I/R损伤组、PAH72+I/R损伤组大鼠血清cTnI、CK水平低于PAH18+I/R损伤组,PAH72+I/R损伤组大鼠血清LDH水平低于PAH18+I/R损伤组(P<0.05);PAH72+I/R损伤组大鼠血清CK、LDH水平低于PAH36+I/R损伤组(P<0.05)。假手术组大鼠心肌损伤评分为0;PAH36+I/R损伤组、PAH72+I/R损伤组大鼠心肌损伤评分低于I/R损伤组、PAH18+I/R损伤组(P<0.05)。I/R损伤组、PAH36+I/R损伤组大鼠血浆TNF-α、IFN-γ、IL-6水平高于假手术组(P<0.05);PAH36+I/R损伤组大鼠血浆TNF-α、IFN-γ、IL-6水平低于I/R损伤组(P<0.05)。结论 PAH可通过抑制炎症反应来减轻心肌I/R损伤大鼠的心肌损伤程度,进而发挥心肌保护作用,且其最佳剂量为36 mg/kg。

Abstract：

【Abstract】　Background After acute myocardial infarction, criminal blood vessels can be opened throughinterventional therapy to save dying myocardium, but neutrophil infiltration and endothelial cell dysfunction will lead tomyocardial ischemia/reperfusion (I/R) injury. Mobilizing endogenous protective mechanism through drugs is an important strategyto combat myocardial I/R injury. Perillaldehyde (PAH) has strong anti-inflammatory and antifungal effects, but its effect onmyocardial I/R injury is not clear. Objective To investigate the protective mechanism and optimal dose of PAH on myocardialI/R injury in rats. Methods From June 2020 to June 2021, 20 rats were selected from 32 SPF adult male Sprague-Dawley ratsand randomly divided into Sham group, I/R injury group, PAH18+I/R injury group, PAH36+I/R injury group and PAH72+I/Rinjury group, with 4 rats in each group. The Sham group and I/R injury group were given 0.5% carboxycellulose continuous gastricperfusion for 1 week, and the PAH18+I/R injury group, PAH36+I/R injury group and PAH72+I/R injury group were given PAH of18, 36 and 72 mg/kg respectively for 1 week, and then the myocardial I/R model was established in I/R injury group, PAH18+I/Rinjury group, PAH36+I/R injury group and PAH72+I/R injury group, and the Sham group underwent the same operation, but onlythreading without ligation. The levels of serum cardiac troponin I (cTnI) , creatine kinase (CK) , lactate dehydrogenase (LDH) andmyocardial injury score were compared among the five groups. The remaining 12 rats were randomly divided into Sham group,I/R injury group, and PAH36+I/R injury group, with 4 rats in each group, and the intervention method was the same as above.The levels of tumor necrosis factor (TNF) -α, interferon (IFN) -γ and interleukin (IL) -6 in plasma were compared among thethree groups.Results The levels of serum cTnI, CK and LDH in I/R injury group, PAH18+I/R injury group, PAH36+I/R injurygroup and PAH72+I/R injury group were higher than those in Sham group (P < 0.05) ; the levels of serum cTnI in the PAH36+I/Rinjury group and PAH72+I/R injury group were lower than those in the I/R injury group, while the levels of serum CK and LDHin PAH18+I/R injury group, PAH36+I/R injury group and PAH72+I/R injury group were lower than those in I/R injury group (P< 0.05) ; the levels of serum cTnI and CK in the PAH36+I/R injury group and PAH72+I/R injury group were lower than those inthe PAH18+I/R injury group, and the level of serum LDH in the PAH72+I/R injury group was lower than that in the PAH18+I/Rinjury group (P < 0.05) ; the serum levels of CK and LDH in the PAH72+I/R injury group were lower than those in the PAH36+I/Rinjury group (P < 0.05) . The myocardial injury score of the rats in the Sham group was 0; the myocardial injury scores of rats inPAH36+I/R injury group and PAH72+I/R injury group were lower than those in I/R injury group and PAH18+I/R injury group (P< 0.05) . The levels of TNF-α, IFN-γ and IL-6 in plasma of the rats in the I/R injury group and PAH36+I/R injury group werehigher than those in the Sham group (P < 0.05) ; the levels of TNF-α, IFN-γ and IL-6 in plasma of the PAH36+I/R injury groupwere lower than those of the I/R injury group (P < 0.05) . Conclusion PAH can reduce the degree of myocardial injury in ratswith myocardial I/R injury by inhibiting inflammatory response, and then play a myocardial protective role, and the optimal dose is36 mg/kg.

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