荔枝壳原花青素对脓毒症大鼠心肌细胞凋亡的作用及其机制研究  

Protective effects of LPPC on cardiomyocyte apoptosis in septic rats

作　　者：张晓晖[1] 孙智达[2] 李书艺[3] 曾繁典[4] 熊益群[1] 徐超英[1] 刘心亮[1] 林坚[1] 穆桂萍[1] 徐绍钢[1] 刘文赫[1] 

机构地区：[1]深圳市中医院中医药研究所,广东深圳518033 [2]华中农业大学食品科学技术学院,湖北武汉430070 [3]武汉轻工大学食品科学与工程学院,湖北武汉430023 [4]华中科技大学同济医学院药理系,湖北武汉430030

出　　处：《中国药理学通报》2015年第7期931-935,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81101450);深圳市科技研发资金知识创新计划资助项目(No JCYJ20130329155553734)

摘　　要：目的研究荔枝壳原花青素(Procyanidins extracted from the litchi pericarp,LPPC)对脓毒症大鼠心肌细胞凋亡的作用及其机制。方法实验大鼠随机分为5组,连续灌胃两周:空白对照组(control)和脓毒症模型组(LPS)每天给予蒸馏水灌胃1次;LPPC低、中、高剂量组分别每天给予新鲜配制的LPPC 50,100,200 mg·kg-1·d-1灌胃1次。给药结束后,建立脓毒症动物模型。即除空白对照组外所有大鼠腹腔内注射LPS(lipopolysacchride,10mg·kg-1,ip)诱导急性脓毒症模型。4 h后收集大鼠血清,检测血清同工酶(CKMB)、乳酸脱氢酶(LDH)和谷草转氨酶(AST/GOT)的活力。取大鼠心肌组织,测定心肌组织丙二醛(MDA)、总抗氧化能力(T-AOC)和还原型谷胱甘肽(GSH)含量。TUNEL染色观察大鼠心肌细胞凋亡情况。Western blot法检测凋亡相关蛋白Cleaved caspase-3及TNF-α水平。结果与正常对照组(control)比较,脓毒症模型组大鼠血清CK-MB、LDH、AST/GOT以及心肌组织MDA含量均明显升高(P<0.01);同时,心肌组织T-AOC和GSH的活力明显降低(P<0.01);凋亡心肌细胞数量明显增加(P<0.01);Cleaved caspase-3及TNF-α表达水平明显下降(P<0.01)。LPPC预处理明显降低了大鼠血清CK-MB、LDH、AST/GOT以及心肌组织MDA含量;增加了大鼠心肌组织T-AOC和GSH的活力;凋亡心肌细胞数量明显减少;Cleaved caspase-3及TNF-α表达水平明显下降。结论荔枝壳原花青素预处理能够明显减轻脓毒症大鼠心肌细胞凋亡,可能与其抗氧化性损伤作用有关。Aim To explore the protective effects of LPPC ( procyanidins extracted from the litchi pericarp) on cardiomyocyte apoptosis in septic rats and its mech-anisms. Methods The rats were randomly divided in-to 5 groups, and were given orally the drug for two weeks continuously. The control group ( control) and sepsis model group ( LPS ) were given distilled water once a day. LPPC low, medium and high dose groups were given LPPC 50 , 100 , 200 mg · kg-1 · d-1 re-spectively which were prepared freshly every day. After the treatment, sepsis animal models were established. Except for the control group, other groups were injec-ted LPS (lipopolysacchride, 10mg·kg-1) intraperito-neally to induce acute sepsis model. 4hrs later, rat se-rum was collected, isoenzyme ( CK-MB ) , lactate de-hydrogenase ( LDH ) and activity of aspertate amin-otransferase ( AST/GOT) were detected. Then rat car-diac tissue was obtained and cardiac tissue malondial-dehyde ( MDA ) , total antioxidant capacity ( T-AOC ) and reduced glutathione ( GSH ) content were deter-mined. TUNEL staining was performed to analyze the apoptosis of myocardial cells. Cleaved caspase-3 and TNF alpha protein expressions were analyzed by West-ern blot. Results Compared with the control group ( control) , serum of sepsis model group rats CK-MB, LDH, AST/GOT and cardiac tissue MDA content were significantly increased (P<0. 01). At the same time, the activity of cardiac tissue T-AOC and GSH de-creased obviously ( P<0. 01 ) . The apoptotic myocar-dial cells increased significantly ( P<0. 01 ) , and the expression level of cleaved caspase-3 and TNF alpha decreased obviously ( P <0. 01 ) . LPPC pretreatment significantly decreased the serum CK-MB, LDH, AST/GOT and tissue MDA content, increased tissue T AOC and GSH activity, attenuated apoptosis of rat myocardi-al cells significantly, and decreased expression level of cleaved caspase-3 and TNF alpha. Conclusion LPPC pretreatment can significantly attenuate rat myocardial cell apoptosis induced by sepsis, and the underlying mec

关 键 词：荔枝壳原花青素 脓毒症 心肌细胞 凋亡 氧化应激 大鼠 

分 类 号：R-332[医药卫生] R284.1