白藜芦醇通过抑制细胞凋亡和自噬减轻川崎病诱发的心肌损伤  

Resveratrol alleviates Kawasaki disease-induced myocardial injury via inhibition of apoptosis and autophagy

作　　者：熊凤梅[1] 刘瑞萍[2] 郭焕利[1] 武冬梅[1] 孙娜[3] XIONG Fengmei;LIU Ruiping;GUO Huanli;WU Dongmei;SUN Na(Department of Pharmacy,Xi'an Children's Hospital,Xi'an 710003;Department of Nutrition,Xi'an Children's Hospital,Xi'an 710003;Institute of Basic Medical Science,Xi'an Medical University,Xi'an 710021,China)

机构地区：[1]西安市儿童医院药剂科,西安710003 [2]西安市儿童医院营养科,西安710003 [3]西安医学院基础医学研究所,西安710021

出　　处：《中南大学学报（医学版）》2021年第10期1102-1108,共7页Journal of Central South University ：Medical Science

基　　金：西安市科技计划项目(201805098YX6SF32-6);西安市儿童医院院级课题(2020C01)。

摘　　要：目的:探讨白藜芦醇(resveratrol,Res)在川崎病(Kawasaki disease,KD)诱发心肌损伤中的作用及其对细胞凋亡和自噬的调控作用。方法:将48只幼年雄性Sprague Dawley大鼠(4周龄)随机分为对照组、Res对照组(Res组)、干酪乳酸杆菌细胞壁提取物(lactobacillus casei cell wall extract,LCWE)注射模拟KD组(KD组)以及LCWE注射模拟+Res处理组(Res+KD组)。对照组腹腔注射生理盐水,Res组腹腔注射Res(100 mg/kg),KD组腹腔注射LCWE(1 mg/mL), Res+KD组腹腔注射LCWE(1 mg/mL)和Res(100 mg/kg)。4周后,采用超声检测左室射血分数(left ventricular ejection fraction,LVEF)和短轴缩短率(left ventricular fraction shortening,LVFS);采用原位末端标记法(terminal-deoxynucleoitidyl transferase mediated nick end labeling,TUNEL)染色观察细胞凋亡的变化;采用蛋白质印迹法检测心肌组织中B细胞淋巴瘤2(B-cell lymphoma-2,Bcl-2)、Bcl-2关联X蛋白(Bcl-2-associated X protein,Bax)、微管相关蛋白轻链3β(microtubule-associated protein 1 light chain 3β,LC3B)、自噬关键分子酵母Atg6同系物(Beclin 1)、自噬相关蛋白5(autophagy related 5,Atg5)和选择性自噬接头蛋白(sequestosone-1,p62)表达,并在透射电镜下观察自噬小体的形成。结果:与对照组相比,Res组各项指标差异均无统计学意义(均P>0.05);KD组LVEF和LVFS均明显降低(均P<0.01),Bax/Bcl-2比值和TUNEL染色阳性细胞均明显增加(均P<0.01),而LC3BII/LC3BI比值、Beclin 1、Atg5和p62表达也均显著增加(均P<0.01),自噬小体增多;与KD组相比,Res+KD组LVEF和LVFS均增加(均P<0.01),Bax/Bcl-2比值和TUNEL染色阳性细胞均减少(均P<0.01),LC3BII/LC3BI比值、Beclin1、Atg5和p62表达也均显著降低(均P<0.01),自噬小体的形成明显受到抑制。结论:Res能够通过抑制细胞凋亡和自噬减轻KD引起的心肌损伤。Objective: To explore the effect of resveratrol(Res) on Kawasaki disease(KD)-induced myocardial injury and to evaluate its effect on apoptosis and autophagy.Methods: Forty-eight juvenile male Sprague Dawley rats were randomly divided into a control group, a Res group, a lactobacillus casei cell wall extract(LCWE)-induced Kawasaki disease group(KD group), and a LCWE-induced Kawasaki disease + Res treatment group(Res+KD group). The control group was intraperitoneally injected with saline. The Res group was intraperitoneally injected with resveratrol(100 mg/kg). The KD group was intraperitoneally injected with 0.5 mL LCWE(1 mg/mL). The Res+KD group was intraperitoneally injected with 0.5 mL LCWE(1 mg/mL) and resveratrol(100 mg/kg).After 4 weeks, the left ventricular ejection fraction(LVEF) and short axis shortening rate(LVFS) were detected by echocardiography. The apoptotic rate was detected by terminaldeoxynucleoitidyl transferase mediated nick end labeling(TUNEL) staining. The levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), microtubule-associated protein 1 light chain 3β(LC3B), Beclin-1, autophagy related 5(Atg5) and sequestosome-1(p62) were detected by Western blotting. The formation of autophagosome was observed under transmission electron microscope.Results: There was no significant difference in the above-mentioned indexes between the control group and the Res group(all P>0.05). Compared with the control group, the values of LVEF and LVFS were significantly decreased in the KD group(both P<0.01);the ratio of Bax/Bcl-2 and TUNEL-positive cells were increased(both P<0.01);the LC3BII/LC3BI ratio, the levels of Beclin 1, Atg5 and p62, and the number of autophagosomes were also significantly increased in KD group(all P<0.01). Compared with the KD group, the values of LVEF and LVFS were significantly increased, the ratio of Bax/Bcl-2 and TUNELpositive cells were decreased, the LC3BII/LC3BI ratio, the levels of Beclin 1, Atg5 and p62 were all decreased(all P<0.01), and the number of autophagosom

关 键 词：川崎病 白藜芦醇 自噬 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]