丹酚酸B保护大鼠缺血心肌与炎症小体NLRP3表达的相关性研究  

Protective effects of salvianolic acid B on isoproterenol induced myocardial ischemic rats and its relation with NLRP3 expression

作　　者：王新宇[1] 王曼[1] 孙帅军 陈叶香[1] 蒋宝平[1] 许立[1] 

机构地区：[1]南京中医药大学药学院,江苏省中药药效与安全性评价重点实验室,江苏南京210023

出　　处：《中国药理学通报》2016年第10期1383-1388,共6页Chinese Pharmacological Bulletin

基　　金：科技部“重大新药创制”重大科技专项(No 2011ZX09102-002-07);江苏高校品牌专业建设工程资助项目(No PPZY2015A070)

摘　　要：目的探讨丹酚酸B(salvianolic acid B,Sal B)对异丙肾上腺素(isoproterenol,ISO)所致心肌缺血损伤的保护作用及炎症小体NLRP3(NLR family,pyrin domain containing 3)相关蛋白的表达对心肌缺血的影响。方法♂SD大鼠随机分为对照组、模型组和Sal B低、中、高剂量组。Sal B各剂量组腹腔注射给予Sal B 5、10、15 mg·kg^(-1),模型组和对照组腹腔注射等体积生理盐水,各组连续给药7 d;从d 5开始,皮下多点注射ISO(30 mg·kg^(-1)),连续2 d造模。末次造模24 h后观察Sal B对大鼠心电图、血清中心肌酶、氧化指标和炎症因子含量、心肌组织中炎症小体NLRP3相关蛋白表达及形态学的影响。结果 Sal B可以明显减轻心肌组织坏死和炎细胞浸润,明显降低心电图中T波值(P<0.05,P<0.01)。与模型组比较,Sal B各剂量组的肌酸激酶(creatine kinase,CK)值、谷草转氨酶(glutamic oxalacetic transaminase,GOT)值和白细胞介素1-β(interleukin 1-β,IL-1β)值,Sal B中、高剂量组的丙二醛(malonaldehyde,MDA)值及中剂量组的乳酸脱氢酶(lactic dehydrogenase,LDH)值均明显降低(P<0.05,P<0.01);血清Sal B中、高剂量组的总超氧化物歧化酶(total superoxide dismutase,T-SOD)值明显升高(P<0.05,P<0.01);Sal B给药组的心脏组织中NLRP3、半胱氨酸蛋白酶1(cysteinyl aspartate specific protease-1,caspase-1)和IL-1β蛋白表达明显降低(P<0.05,P<0.01)。结论 Sal B具有抗ISO所致大鼠心肌缺血作用,该作用机制可能与调控炎症小体NLRP3相关蛋白表达,抑制炎症因子的生成有关。Aim To evaluate the protective effects of salvianolic acid B on the ISO-induced myocardial is-chemic injury model of rats and the influence of regula-ting NLRP3 associated protein on myocardial ischemia. Method All rats were randomly divided into control group, model group and Sal B 5, 10, 15 mg ·kg^-1 groups. For 7 days, rats in Sal B groups were given by introperitoneal injection of 5, 10, 15 mg＆#183;kg-1 Sal B, rats in control group and model group were given the same volume of normal saline. Rats were subcutane-ously multi-point injected ISO （ 30 mg ·kg^-1 ） for 2 days on the fifth administrating day. The myocardial protective effect of Sal B was evaluated from electrocar-diogram（ ECG）, myocardial tissue pathological chan-ges, serum myocardial enzymes, oxidation index and inflammatory cytokine, myocardial tissue of NLRP3 related protein expression. Results Sal B could re-duce the degree of myocardial tissue necrosis and the infiltration of inflammatory cells, reduce T-wave values of ECG（P〈0. 05 or P〈0. 01）. Compared with model group, CK values, GOT values and IL-1β values of rats in different dose groups were significantly lower, and MDA values and LDH values of rats in middle-and high-dose groups were significantly lower （ P〈0. 05 or P〈0. 01 ） . However, T-SOD values of rats middle-and high-dose groups were significantly higher （ P 〈0. 05 or P〈0. 01）. Meanwhile,the NLRP3, Caspase-1 and IL-1β protein level in myocardial tissue of the rats in different dose groups compared with model group had reduced （ P 〈0. 05 or P 〈0. 01 ） . Conclu-sion Sal B has protective effects on myocardial ische-mic rats, its mechanism may be related with inhibition of decreasing the expression of NLRP3 inflammasome associated protein, which can suppress the generation of inflammatory cytokines.

关 键 词：丹酚酸B NLRP3 异丙肾上腺素 心肌缺血 白细胞介素1-Β 心肌酶 

分 类 号：R-332[医药卫生] R284.1