摘要
目的观察半夏厚朴汤对慢性间歇性低氧(chronic intermittent hypoxia,CIH)模型小鼠心脏损伤和内质网应激水平的调节作用。方法将30只SPF级雄性小鼠随机分为正常组、CIH模型组、半夏厚朴汤治疗组(治疗组),每组10只。使用慢性间歇性低氧舱建立CIH动物模型,治疗组给予半夏厚朴汤灌胃7.02 g/(kg·天),造模21天后取材。(1)小动物B超检测各组小鼠心功能,包括射血分数(ejection fraction,EF)、左心室收缩末期内径(LV-End systolic diameter,LVESD)、左心室舒张末期内径(LV-End diastolic diameter,LVEDD)。(2)使用全自动生化分析仪测定各组小鼠肌酸激酶(creatine kinase,CK)、肌酸激酶同工酶(creatine kinase-MB,CK-MB)、乳酸脱氢酶同工酶1(lactic dehydrogenase isoenzyme 1,LDH1)的含量。(3)使用比色法检测各组小鼠组织中超氧化物歧化酶(superoxide Dismutase,SOD)、丙二醛(malondialdehyde,MDA)、过氧化氢酶(catalase,CAT)的含量。(4)Western blot检测各组小鼠心脏组织中葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)、内质网氧化还原1样蛋白(endoplasmic reticulum oxidoreductin-1-like protein,ERO1L)的表达。(5)TUNEL染色观察心肌细胞中凋亡小体数量。结果(1)与正常组相比,模型组小鼠心脏左心室EF下降,LVESD、LVEDD均有不同程度的升高(P<0.05);与模型组相比,治疗组可以改善心功能(P<0.05)。(2)与正常组相比,模型组小鼠心脏CK、CK-MB、LDH1等心肌酶水平明显上升(P<0.05);与模型组相比,治疗组心肌酶水平明显下降(P<0.05)。(3)与正常组比较,模型组小鼠血清中SOD和CAT活性明显下降,MDA含量明显上升(P<0.05);与模型组相比,治疗组小鼠SOD和CAT活性上升,MDA含量减少(P<0.05)。(4)与正常组比较,模型组小鼠GRP78、CHOP、ERO1L等蛋白表达升高(P<0.05);与模型组相比,治疗组小鼠蛋白水平明显下调(P<0.05)。(5)与正常组相比,模型组小鼠凋亡小体数量明显增加;与模型组相比,治疗组小鼠心脏中凋亡小体数量明显减少。结论半夏厚朴汤可能通过抑制慢性间歇性低氧暴露引起的内质网应激,进而减轻心脏细胞凋亡,改善心功能。
Objective To investigate the effects of Banxia Huopu decoction on cardiac injury and endoplasmic reticulum stress in mice with chronic intermittent hypoxia(CIH).Methods Thirty SPF male mice were randomly divided into normal group,chronic intermittent hypoxia(CIH)model group and Banxia Huopu decoction treatment group(treatment group),with 10 mice in each group.The CIH animal model was established by chronic intermittent hypoxia chamber.The treatment group was given Banxia Huopu decoction[7.02 g/(kg·d)]by gavage.(1)Cardiac function,including Ejection fraction(EF),left ventricular end-systolic diameter(LVESD)and left ventricular End diastolic diameter(LVEDD)were detected by B-ultrasound.(2)creatine kinase(CK),creatine kinase-MB(CK-MB)and lactate dehydrogenase isoenzyme1(LDH1)were determined by automatic biochemical analyzer.(3)The contents of Superoxide Dismutase(SOD),malondialdehyde(MDA)and catalase(CAT)in serum of mice were detected by colorimetric method.(4)The method of Western blot was used to detect Glucose-regulated protein 78(GRP78),CCAAT/enhancer-binding protein homologous protein(CHOP),endoplasmic reticulum oxidoreductin-1-like protein(ERO1L)in heart tissues of mice in each group.(5)The number of apoptotic bodies in cardiomyocytes was observed by TUNEL staining.Results(1)Echocardiography showed that compared with the normal group,the left ventricular ejection fraction of the heart in the model group was decreased,and the left ventricular end-systolic and diastolic diameters were increased(P<0.05).Compared with the model group,the cardiac function was improved in the treatment group(P<0.05).(2)Compared with the normal group,the levels of cardiac enzymes such as CK,CK-MB and LDH1 in the model group were significantly increased(P<0.05).Compared with the model group,the levels of myocardial enzymes in the treatment group were significantly decreased(P<0.05).(3)Compared with the normal group,the activities of SOD and CAT in tissues of the model group were significantly decreased,and the content of MDA was significantly increased(P<0.05).Compared with the model group,the levels of SOD and CAT were increased,and the content of MDA was decreased in the treatment group(P<0.05).(4)The results of Western blot showed that the protein expressions of GRP78,CHOP and ERO1L in the model group were increased compared with the normal group(P<0.05),and the protein levels of the treatment group were significantly down-regulated compared with the model group(P<0.05).(5)The results of TUNEL staining showed that the number of apoptotic bodies in the model group was significantly increased compared with the normal group,and the number of apoptotic bodies in the heart of the treatment group was significantly decreased compared with the model group.Conclusion Banxia Houpu decoction may reduce cardiac cell apoptosis and improve cardiac function by inhibiting endoplasmic reticulum stress induced by chronic intermittent hypoxia exposure.
作者
宋纪显
陈琦
杨新栎
安继仁
赵亚硕
吉恩生
SONG Jixian;CHEN Qi;YANG Xinyue;AN Jiren;ZHAO Yashuo;JI Ensheng(Hebei University of Chinese Medicine,Shijiazhuang 050200,China)
出处
《环球中医药》
CAS
2023年第9期1729-1734,共6页
Global Traditional Chinese Medicine
基金
国家自然科学基金(82004127)
河北省中医药管理局科研计划(Z2022005)。
关键词
半夏厚朴汤
阻塞性睡眠呼吸暂停
慢性间歇性低氧
氧化应激
内质网应激
小鼠心脏损伤
Banxia Houpu decoction
obstructive sleep apnea
chronic intermittent hypoxia
oxidative stress
endoplasmic reticulum stress
heart injury in mice
