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陈聪,任婷,胡华,黄政德,廖菁.加味丹参饮预处理对大鼠心肌缺血再灌注损伤的保护作用[J].湖南中医药大学学报,2016,36(6):11-15[点击复制] |
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加味丹参饮预处理对大鼠心肌缺血再灌注损伤的保护作用 |
陈聪,任婷,胡华,黄政德,廖菁 |
(湖南中医药大学, 湖南 长沙 410208) |
摘要: |
目的 探讨加味丹参饮(JDSH)预处理对大鼠心肌缺血再灌注损伤(IRI)的保护作用及机制。方法 采用结扎大鼠冠状动脉左前降支30 min后再灌注30/60 min模型,将56只SD雄性大鼠随机分为7组:假手术组、缺血/再灌注(I/R)30 min组、I/R 60 min组、p38MAPK阻断剂SB203580+I/R 30 min组、SB203580+I/R 60 min组、JDSH+I/R 30 min组、JDSH+I/R60 min组。各组干预2 d后,HE染色心肌组织标本,全自动生化分析仪测定血清CK、LDH,免疫组化法检测p38MAPK、COX-2和ICAM-1蛋白的表达。结果 经JDSH预处理或p38MAPK阻断剂SB203580处理后心肌细胞形态结构保持更好。与假手术组比较,I/R30 min组和I/R 60min组大鼠血清中的CK、LDH明显升高(P<0.01);与I/R 30/60 min比较,SB203580+I/R 30/60 min组和JDSH+I/R 30/60 min组均明显降低(P<0.01)。与假手术组比较,I/R使大鼠心肌组织的p38MAPK、COX-2、ICAM-1蛋白表达增加(P<0.01),且随再灌注时间的延长而增加;与I/R 30/60 min组比较,SB203580和JDSH均能减少其蛋白表达(P<0.01)。结论 大鼠心肌IRI时,激活了p38MAPK信号通路,且与再灌注时间(30~60 min)呈正相关。JDSH通过抑制p38MAPK信号通路,降低其下游基因COX-2和ICAM-1的表达,降低CK、LDH,减轻心肌损伤,起到保护心肌作用。 |
关键词: 加味丹参饮 心肌 缺血再灌注 p38MAPK COX-2 ICAM-1 丹参 檀香 赤芍 |
DOI:10.3969/j.issn.1674-070X.2016.06.004 |
投稿时间:2016-01-14 |
基金项目:国家自然科学基金资助项目(81373576,81503536);湖南省教育厅科学研究项目(14C0872,14B136);湖南省科技厅科学研究项目(2014SK3034);湖南省中医药科研计划课题(B0347);中西医结合防治心脑疾病的相关基础研究湖南省高校科技创新团队科研项目(5);中医内科学省部共建教育部重点实验室开放基金重点项目(ZYNK201401)。 |
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Protective Effects of Modified Danshen Decoction Pretreatment on Myocardial Ischemia Reperfusion Injury in Rats |
CHEN Cong,REN Ting,HU Hua,HUANG Zhengde,LIAO Jing |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
Abstract: |
Objective To investigate the protective effects of Jiawei Danshen decoction (JDSH) pretreatment on myocardial ischemia reperfusion injury (IRI) in rats and its molecular mechanisms. Methods The models of left anterior descending coronary artery of ligatured rats for 30 mins and then I/R 30 (or I/R 60) mins were built, fifty-six male SD rats were randomly divided into 7 groups:sham operation group, ischemia reperfusion (I/R) injury for 30 min group (I/R 30),I/R for 60 mins (I/R 60) group, p38MAPK inhibitor SB203580 with I/R30 mins (SB203580+I/R30) group, SB203580+I/R 60 group, JDSH+I/R 30 group, JDSH+I/R 60 group. After intervention for two days, the myocardial tissue was observed with HE Dyeing, the serum CK and LDH were measured by the automatic biochemical analyzer, the expression of p38MAPK, COX-2, ICAM-1 were determined by immunohistochemical assay. Results The cardiomyocytes' morphological structure with JDSH or p38MAPK inhibitor SB203580 pretreatment was better. Compared with sham operation group, the content of CK and LDH in serum of I/R 30 and I/R 60 groups was increased obviously (P<0.01). Compared with I/R 30 and I/R60 groups, the SB 203580+I/R30 or 60 and JDSH+I/R30 or 60 groups were reduced distinctly (P<0.01). Compared with sham operation group, the myocardial tissue p38MAPK, COX-2, ICAM-1 protein expression in I/R rats were increased (P<0.01), and increased with the extension of reperfusion time. Compared with I/R 30/60 groups, the protein expression in SB203580 and JDSH groups was decreased (P<0.01). Conclusion Myocardial IRI in rats activates the p38MAPK signaling pathway which is positively correlated with reperfusion time (30 min to 60 min). JDSH can alleviate the myocardial damage by inhibition of the p38MAPK signaling pathway, reducing the expression of the COX-2 and ICAM-1, and CK, LDH, to protect ischemic heart muscle. |
Key words: modified Danshen decoction myocardium Ischemia reperfusion p38MAPK COX-2 ICAM-1 Salvia miltiorrhiza Bge. Santalum album L. Paeonia veitchii Lynch |
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