摘要
目的 探讨麦冬皂苷D(OPD)对脓毒症大鼠心肌损伤及磷酸酶及张力蛋白同源物诱导激酶1/帕金蛋白(PINK1/parkin)通路的影响。方法 用盲肠结扎穿孔法构建脓毒症大鼠模型,并将造模成功的大鼠随机分为模型组、实验组、对照组和联合组,每组8只。在模型制备成功后12 h,实验组给予腹腔注射40 mg·kg^(-1)OPD,对照组给予腹腔注射20 mg·kg^(-1)3-MA,联合组给予腹腔注射40 mg·kg^(-1)OPD和20 mg·kg^(-1)3-MA;假手术组和模型组均给予腹腔注射等量0.9%NaCl。5组大鼠每12 h重复给药1次,连续给药6 d。用酶联免疫吸附试验法检测血清肌钙蛋白Ⅰ(cTnⅠ)水平,用蛋白质印迹法检测大鼠心肌组织中PINK1和parkin蛋白的表达水平。结果 实验组、对照组、联合组、模型组和假手术组的血清cTnⅠ水平分别为(0.98±0.20)、(3.44±0.69)、(1.64±0.38)、(2.39±0.45)和(0.37±0.07)mg·L^(-1),PINK1蛋白相对表达水平分别为1.73±0.35、0.55±0.11、0.91±0.20、0.83±0.15和0.28±0.05,parkin1蛋白相对表达水平分别为1.78±0.36、0.63±0.12、0.96±0.22、0.94±0.17和0.30±0.06。实验组、对照组和假手术组的上述指标与模型组相比,实验组和对照组的上述指标与联合组相比,差异均有统计学意义(均P<0.05)。结论 OPD缓解脓毒症引起的大鼠心肌损伤可能是通过激活PINK1/parkin通路促进线粒体自噬实现的。
Objective To investigate the effects of Ophiopogonin D(OPD)on myocardial injury and phosphatase and tensin homolog induced putative kinase 1/parkin pathway(PINK1/parkin)in septic rats.Methods The sepsis rat model was constructed by cecal ligation and perforation method,and the successfully constructed rats were randomly divided into model group,experimental group(40 mg·kg^(-1) OPD),control group(20 mg·kg^(-1)3-MA),and combination group(40 mg·kg^(-1) OPD+20 mg·kg^(-1)3-MA)with 8 rats in each group.Another 8 normal rats were selected as sham-operation group.12 h after the completion of modeling,the experimental group,control group and combination group were given intraperitoneal injection according to the dosage of each group,and the sham-operation group and model group were only given intraperitoneal injection of 0. 9%NaCl. The rats in the 5 groups were given the drug once every 12 h for6 days. The serum troponin Ⅰ ( cTnⅠ) levels were detected by enzyme - linked immunosorbent assay 24 h after thelast administration,and the expression levels of PINK1 and parkin proteins were detected by western blotting. ResultsThe serum cTn Ⅰ levels in the experimental,control,combined,model and sham - operation groups were( 0. 98 ± 0. 20) ,( 3. 44 ± 0. 69 ) ,( 1. 64 ± 0. 38 ) ,( 2. 39 ± 0. 45 ) and ( 0. 37 ± 0. 07 ) mg·L^(-1);the relativeexpression levels of PINK1 protein in myocardium were 1. 73 ± 0. 35,0. 55 ± 0. 11,0. 91 ± 0. 20,0. 83 ± 0. 15 and0. 28 ± 0. 05;the relative expression levels of parkin1 protein were 1. 78 ± 0. 36,0. 63 ± 0. 12,0. 96 ± 0. 22,0. 94 ± 0. 17 and 0. 30 ± 0. 06,respectively. Compared the experimental,control and sham - operation groups with themodel group,compared the experimental and control groups with combined group,the differences of above indexeswere statistically significant ( all P < 0. 05) . Conclusion OPD alleviates sepsis - induced myocardial injury in rats,which may be achieved through the activation of PINK1 /parkin pathway to promote mitochondrial autophagy.
作者
辛颖
员丽培
王峰
杨宏富
XIN Ying;YUAN Li-pei;WANG Feng;YANG Hong-fu(Department of Cardiology,Xuchang Central Hospital Affiliated to Henan University of Science and Technology,Xuchang 461000,Henan Province,China;Department of General Surgery,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,Henan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第7期971-975,共5页
The Chinese Journal of Clinical Pharmacology
基金
河南省科技攻关计划课题资助项目(LHGJ20190213)。
