摘要
目的观察天香丹胶囊预处理对去卵巢合并心肌缺血再灌注(I/R)大鼠心肌损伤的保护作用。方法将60只SD雌性大鼠摘去卵巢后随机分为假手术组、模型组、对照组和低、中、高剂量实验组,每组10只。假手术组和模型组均灌胃给予等量双蒸水;对照组按0.8 mg·kg^(-1)的剂量灌胃给予雌二醇溶液;低、中、高剂量实验组分别按200.0、400.0和800.0 mg·kg^(-1)的剂量灌胃给予天香丹溶液。6组大鼠连续给药60 d。末次给药12 h后,建立缺血再灌注模型;其中假手术组只穿线不结扎。另取10只正常SD雌性大鼠为正常组(不做任何处理)。用伊文氏蓝-氯化三苯基四氮唑双重染色检测大鼠心肌梗死率,用蛋白质印迹法检测组织中活化胱天蛋白酶-3(cleaved-caspase-3)、环腺苷酸反应元件结合蛋白(CREB)等相关蛋白的表达情况。结果高剂量实验组、对照组、模型组、假手术组和正常组的心肌梗死率分别为(21.61±2.74)%、(22.08±4.68)%、(61.84±3.92)%、(1.02±0.02)%和(0.85±0.13)%,cleaved caspase-3蛋白相对表达水平分别为0.52±0.03、0.70±0.05、0.98±0.03、0.54±0.07和0.44±0.03,磷酸化CREB蛋白相对表达水平分别为1.12±0.06、1.16±0.04、0.70±0.05、1.32±0.04和1.45±0.03。模型组的上述指标与高剂量实验组、对照组、假手术组和正常组相比,差异均有统计学意义(P<0.05或P<0.01)。结论天香丹胶囊预处理可以改善I/R引起的大鼠心肌损伤,其作用机制可能是上调环腺苷酸/蛋白激酶A/环腺苷酸反应元件结合蛋白(cAMP/PKA/CREB)通路相关蛋白表达,下调cleaved-caspase-3蛋白表达,进而实现抑制心肌细胞凋亡。
Objective To observe the protective effect of Tianxiangdan capsules pretreatment on myocardial injury in ovariectomized rats with myocardial ischemia/reperfusion(I/R).Methods A total of 60 female SD rats after ovariectomy were randomly divided into sham-operation group,model group,control group and experimental-L,-M,-H groups,10 rats in each group.The control group was given 0.8mg·kg^(-1)estradiol solution.The experimental-H,-M,-L group was given 800.0,400.0 and 200.0 mg·kg^(-1)Tianxiangdan solution.The sham-operation and model groups were given the same amount of double distilled water.Six groups were administered twice a day for 60days.After the last administration for 12 hours,the cardiac I/R model were established.Among them,the sham-operation group was only threaded without ligation,and 10 normal SDfemale rats were taken as the normal group(without any treatment).Evans blue-2,3,5-tripheyl tetrazolium chloride double staining was used to detect myocardial infarction area in rats.Western blot was used to detect the expression of apoptosis proteins such as activated cysteine protease-3(cleaved-caspase-3),cyclic adenosine monophosphate response element binding protein(CREB)and other related proteins.Results The myocardial infarction rates of experimental-H,control,model,sham-operation and normal groups were(21.61±2.74)%,(22.08±4.68)%,(61.84±3.92)%,(1.02±0.02)%and(0.85±0.13)%;the relative expression levels of cleaved caspase-3proteins were 0.52±0.03,0.70±0.05,0.98±0.03,0.54±0.07 and 0.44±0.03;the relative expression levels of p-CREB proteins were 1.12±0.06,1.16±0.04,0.70±0.05,1.32±0.04 and 1.45±0.03,respectively.The differences of above indexes were statistically significant between the model group and the experimental-H,control,sham-operation and normal groups(P<0.05 or P<0.01).Conclusion Tianxiangdan capsules pretreatment can improve myocardial injury induced by I/R in rats,and the mechanism of action may be through up-regulation of protein level related to cyclic adenosine monophosphate/protei
作者
王慧敏
姜林
杜古加·嘎尔玛
吉钊
岳远佳
WANG Hui-mi;JANG Lin;DUGUJIA·Ga-er-ma;JI Zhao;YUE Yuan-jia(The Fourth Clinical Medical College,Xinjiang Medical University;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Xinjiang Medical University,Urumqi 830054,Xinjiang UygurAutonomous Region,China;Xinjiang Uygur Autonomous Region Key Laboratory of Traditional Chinese Medicine Processing Research,Urumqi 830000,Xinjiang Uygur Autonomous Region,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第14期2054-2059,共6页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(81960699)
省部共建中亚高发病成因与防治国家重点实验室开放课题基金资助项目(SKL-HIDCA-2020-8)。
关键词
天香丹胶囊
心肌缺血再灌注损伤
G蛋白偶联雌激素受体
环腺苷酸/蛋白激酶A/环腺苷酸反应元件结合蛋白
Tianxiangdan capsule
ischemia/reperfusion impairment
G protein-coupled estrogen receptor
cyclic adenosine monophosphate/protein kinase A/cyclic AMP responsive element-binding protein
