摘要
目的探讨丹参酮ⅡA磺酸钠对脓毒症小鼠心功能不全中自噬的作用。方法用盲肠结扎穿孔术建立小鼠脓毒症模型。将雄性C57BL6小鼠随机分为假手术组、模型组和低、高剂量实验组,每组5只。低、高剂量实验组术前3 h分别按15和45 mg·kg^(-1)的剂量腹腔注射10 mg·mL^(-1)丹参酮ⅡA磺酸钠;假手术组和模型组均给予等量无菌0.9%NaCl。假手术组切开腹壁、暴露盲肠而不结扎穿孔,其余3组行盲肠结扎穿孔术。用酶联免疫吸附试验法检测血清中炎症因子水平,用心脏超声检测小鼠心功能,用TUNEL染色观察心肌细胞凋亡,用蛋白质印迹法观察自噬相关蛋白的表达水平。结果低、高剂量实验组和假手术组、模型组血清中白细胞介素-6(interleukin-6,IL-6)分别为(827.98±24.37),(645.32±15.78),(128.60±17.11)和(1750.21±85.49)pg·mL^(-1),肿瘤坏死因子-α分别为(125.89±7.77),(67.06±9.49),(17.61±4.51)和(156.57±10.65)pg·mL^(-1),IL-1β分别为(167.52±9.93),(157.75±9.63),(25.96±4.30)和(204.30±7.65)pg·mL^(-1),射血分数分别为(53.25±4.43)%,(58.46±3.33)%,(71.98±6.15)%和(49.02±5.26)%,左心室缩短分数分别为(20.24±3.78)%,(22.63±2.22)%,(37.36±3.17)%和(18.26±2.76)%,细胞凋亡指数分别为(6.89±0.51)%,(2.46±0.47)%,(0.56±0.27)%和(10.01±0.61)%,Beclin1蛋白相对表达水平分别为0.70±0.05,0.96±0.04,0.16±0.01和0.27±0.01,P62蛋白相对表达水平分别为0.87±0.02,0.57±0.03,0.25±0.01和0.93±0.03。低、高剂量实验组的上述指标与模型组比较,差异均有统计学意义(P<0.05,P<0.01)。结论丹参酮ⅡA磺酸钠可通过诱导自噬改善脓毒症小鼠心功能不全。
Objective To explore the effect of sodium tanshinoneⅡA sulfonate on autophagy in the mice of septic cardiac dysfunction.Methods The sepsis model of mice were established by cecal ligation and puncture.Male C57 BL6 mice were randomly divided into 4 groups:sham-operation group,model group,experimental-L and-H groups,with 5 mice per group.The experimental-L and-H groups were injected intraperitoneally 10 mg·mL^(-1)sodium tanshinoneⅡA sulfonate at the dose of 15 and 45 mg·kg^(-1) 3 h before operation,respectively.The sham-operation and model groups were given the same amount of sterile 0.9%NaCl.The sham-operation group underwent incision of abdominal wall and exposure of cecum without ligation and perforation,and the other 3 groups underwent ecal ligation and puncture.The level of cytokines in serum was detected by enzyme-linked immunosorbent assay.The cardiomyocyte apoptosis by TUNEL staining.The expression of proteins related to autophagy was assayed by Western blot.Results The levels of interleukin-6(IL-6)in experimental-L and-H groups,sham-operation group and model group were(827.98±24.37),(645.32±15.78),(128.60±17.11)and(1750.21±85.49)pg·m L^(-1),the levels of tumor necrosis factor-αwere(125.89±7.77),(67.06±9.49),(17.61±4.51)and(156.57±10.65)pg·mL^(-1);the levels of IL-1βwere(167.52±9.93),(157.75±9.63),(25.96±4.30)and(204.30±7.65)pg·mL^(-1);the ejection fractions were(53.25±4.43)%,(58.46±3.33)%,(71.98±6.15)%and(49.02±5.26)%,the left ventricular shortening fractions were(20.24±3.78)%,(22.63±2.22)%,(37.36±3.17)%and(18.26±2.76)%;the apoptosis indexes were(6.89±0.51)%,(2.46±0.47)%,(0.56±0.27)%and(10.01±0.61)%;the relative protein expression levels of Beclin1 were 0.70±0.05,0.96±0.04,0.16±0.01 and 0.27±0.01;the relative protein expression levels of P62 were 0.87±0.02,0.57±0.03,0.25±0.01 and 0.93±0.03,respectively.There were significant differences in the indexes between the model group and the experimental-L and-H groups(P<0.05,P<0.01).Conclusion Sodium tanshinoneⅡA sulfon
作者
杨李旺
杨蓉
翟晓艳
赵焕新
季新燕
YANG Li-wang;YANG Rong;ZHAI Xiao-yan;ZHAO Huan-xin;JI Xin-yan(School of Basic Medicine,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第18期2162-2166,共5页
The Chinese Journal of Clinical Pharmacology
基金
山西省自然科学基金资助项目(201901D111340)
山西省中药微乳与生物新制剂研发工程(技术)研究中心开放课题基金资助项目(2019WSZX03)
山西中医药大学科技创新能力培育计划基金资助项目(2019PY-123)。
关键词
丹参酮ⅡA磺酸钠
自噬
脓毒症
心功能不全
sodium tanshinoneⅡA sulfonate
autophagy
sepsis
cardiac dysfunction
