白藜芦醇对糖尿病大鼠心肌缺血再灌注损伤时炎性反应的影响

doi:10.3877/cma.j.issn.2095-9605.2018.03.003

目的

研究白藜芦醇预处理对糖尿病大鼠心肌缺血再灌注损伤的作用，以及对炎性反应的影响。

方法

取糖尿病模型制备成功的SD大鼠30只，采用随机数字表法分为3组（n=10）：假手术组（Sham组）、心肌缺血再灌注组（MI/R组）和心肌缺血再灌注+白藜芦醇组（MI/R+Res组）。B超测量左心室的射血分数（LVEF）以及左室短轴缩短率（FS），于再灌注末时处死5只大鼠，用TTC染色法测定心肌梗死面积，另再处死5只大鼠，经腹主动脉取血测心肌损伤标志物乳酸脱氢酶（LDH）和肌酸激酶同工酶（CK-MB）的浓度，采用ELISA法检测血清的肿瘤坏死因子-α（TNF-α），白介素-6（IL-6），细胞间黏附分子-1（ICAM-1），并取心肌组织，通过RT-PCR法测TNF-α，IL-6，基质金属蛋白酶-9（MMP-9）的含量。

结果

与Sham组比较，MI/R组与MI/R+Res组的LDH和CK-MB浓度，血清TNF-α，IL-6，ICAM-1含量以及心肌梗死面积均显著增高，LVEF和FS显著降低，心肌TNF-α，IL-6，MMP-9的mRNA表达增加（均P<0.05）；与MI/R组比较，MI/R+Res组的LDH和CK-MB浓度，血清TNF-α，IL-6，ICAM-1含量以及心肌梗死面积均显著降低，LVEF和FS显著升高，TNF-α，IL-6，MMP-9的mRNA表达减少（均P<0.05）。

结论

白藜芦醇预处理可以减轻糖尿病大鼠心肌缺血再灌注损伤时的炎性反应。

关键词: 白藜芦醇, 炎性反应, 心肌缺血再灌注, 糖尿病

Objective

To study the effect of resveratrol preconditioning on myocardial ischemia-reperfusion injury in diabetic rats and its effect on inflammatory response.

Methods

Thirty SD rats with successful diabetes model were randomly divided into three groups (n=10): sham operation group (Sham group), myocardial ischemia reperfusion group (MI/R group) and myocardium. Ischemia-reperfusion + resveratrol group (MI/R+Res group). B-ultrasound was used to measure the left ventricular ejection fraction (LVEF) and left ventricular short axis shortening rate (FS). 5 rats were sacrificed at the end of reperfusion, and their myocardial infarct size was determined by TTC staining. Another 5 rats were sacrificed, and the concentration of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) were measured by abdominal aorta blood sampling; the serum tumor necrosis factor-α (TNF-α) were detected by ELISA.; the content of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and myocardial tissue, TNF-α, IL-6, matrix metalloproteinase-9 (MMP-9) by RT-PCR.

Results

Compared with Sham group, LDH and CK-MB concentrations, serum TNF-α, IL-6, ICAM-1 levels and myocardial infarct size significantly increased in the MI/R group and MI/R+Res groups; LVEF and FS significant decreased; and the mRNA expression of myocardial TNF-α, IL-6, MMP-9 increased (both P<0.05). Compared with the MI/R group, LDH and CK-MB concentrations, serum TNF -α, IL-6, ICAM-1 content and myocardial infarct size significantly decreased in the MI/R+Res group, LVEF and FS significantly increased, and the mRNA expressions of TNF-α, IL-6 and MMP-9 decreased (all P<0.05).

Conclusions

Resveratrol preconditioning can reduce the inflammatory response in diabetic rats with myocardial ischemia-reperfusion injury.

Key words: Resveratrol, Inflammatory reaction, Myocardial ischemia-reperfusion, Diabetes

图1 3组大鼠超声图像

表1 3组大鼠的左心室功能指标的比较（±s）

组别	例数	LVEF（%）	FS（%）
Sham组	10	74.03±4.78	40.12±2.31
MI/R组	10	33.41±2.23^a	17.18±1.49^a
MI/R+Res组	10	45.71±4.17^ab	23.16±1.77^ab

表1 3组大鼠的左心室功能指标的比较（±s）

组别	例数	LVEF（%）	FS（%）
Sham组	10	74.03±4.78	40.12±2.31
MI/R组	10	33.41±2.23^a	17.18±1.49^a
MI/R+Res组	10	45.71±4.17^ab	23.16±1.77^ab

表2 3组大鼠的CK-MB、LDH的比较（±s）

组别	例数	CK-MB(pg/ml)	LDH(U/L)
Sham组	10	1894.27±33.35	2488.19±187.19
MI/R组	10	4761.78±510.11^a	7991.81±679.58^a
MI/R+RES组	10	3571.39±232.73^ab	6002.13±663.88^ab

表2 3组大鼠的CK-MB、LDH的比较（±s）

组别	例数	CK-MB(pg/ml)	LDH(U/L)
Sham组	10	1894.27±33.35	2488.19±187.19
MI/R组	10	4761.78±510.11^a	7991.81±679.58^a
MI/R+RES组	10	3571.39±232.73^ab	6002.13±663.88^ab

表3 3组大鼠的TNF-a，IL-6，ICAM-1的比较（±s）

组别	例数	TNF-α(pg/mL)	IL-6（pg/mL）	ICAM-1（ng/mL）
Sham组	10	100.12±6.23	101.78±10.58	11.74±2.11
MI/R组	10	251.34±9.34^a	287.96±7.72^a	30.08±2.19^a
MI/R+RES组	10	200.92±11.87^ab	210.78±10.90^ab	24.61±1.12^ab

表3 3组大鼠的TNF-a，IL-6，ICAM-1的比较（±s）

组别	例数	TNF-α(pg/mL)	IL-6（pg/mL）	ICAM-1（ng/mL）
Sham组	10	100.12±6.23	101.78±10.58	11.74±2.11
MI/R组	10	251.34±9.34^a	287.96±7.72^a	30.08±2.19^a
MI/R+RES组	10	200.92±11.87^ab	210.78±10.90^ab	24.61±1.12^ab

图2 心肌梗死面积图像及数据统计

图3 TNF-α，IL-6和MMP-9 mRNA相对表达量

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Effect of resveratrol on inflammatory response in diabetic rats with myocardial ischemia-reperfusion injury

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Effect of resveratrol on inflammatory response in diabetic rats with myocardial ischemia-reperfusion injury