金丝桃苷改善脓毒症模型大鼠心肌损伤作用机制研究  

Mechanism of Hyperoside Improving Myocardial Injury in Model Rats with Sepsis

作　　者：夏骏 姚晓丽 刘潭 刘伯毅[1] 方志成[1] XIA Jun;YAO Xiaoli;LIU Tan;LIU Boyi;FANG Zhicheng(Department of Intensite Medicine,Taihe Hospital·Afiliated Taihe Hospital of Hubei Unisersity of Medicine,Shiyan,Hubei,China 442000;College of Basic Medicine,Hubei Medical College,Shiyan,Hubei,China 442000)

机构地区：[1]十堰市太和医院.湖北医药学院附属太和医院重症医学科,湖北十堰442000 [2]湖北医药学院基础医学院,湖北十堰442000

出　　处：《中国药业》2021年第5期21-25,共5页China Pharmaceuticals

摘　　要：目的探讨金丝桃苷经缺氧诱导因子-1α/血红素加氧酶-1(HIF-1α/HO-1)信号通路对脓毒症模型大鼠心肌细胞的改善作用。方法将120只SD大鼠随机分为正常对照组(A组,等体积生理盐水)、模型组(B组,等体积生理盐水)、阳性药对照组(C组,地塞米松10 mg/kg)和金丝桃苷低、中、高剂量组(D_1组、D_2组、D_3组,10,20,40 mg/kg),各20只。腹腔注射10%水合氯醛(0.3 mL/kg)建立脓毒症大鼠模型。各组腹腔注射相应药物,给药1次,12 h后处死动物。检测大鼠的血流动力学指标;以酶联免疫吸附(ELISA)法检测血清中心肌肌钙蛋白I(cTnI)、脑钠肽(BNP)和心脏组织匀浆中肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)水平;以苏木精-伊红(HE)染色切片观察心脏结构病理变化;以免疫组化染色法测定大鼠心脏HIF-1α和HO-1蛋白表达水平。结果与A组比较,B组左心室收缩压(LVSP)、左室压最大升高率(+dp/dt_(max))、左室压最大降低率(-dp/dt_(max))、HIF-1α和HO-1水平均显著降低,左心室舒张末压(LVEDP)、cTnI、BNP、TNF-α和IL-1β水平均显著升高(P<0.05);与B组比较,C组、D_1组、D_2组、D_3组的LVSP,+dp/dt_(max),-dp/dt_(max),HIF-1α和HO-1水平均显著升高,LVEDP,cTnI,BNP,TNF-α和IL-1β的水平均显著降低,且呈剂量依赖性(P <0.05)。与C组比较,D_1组、D_2组LVSP,+dp/dt_(max),-dp/dt_(max)均显著降低,LVEDP,cTnI,BNP,TNF-α,IL-1β,HIF-1α,HO-1水平均显著升高(P <0.05),D_3组各指标无显著差异(P>0.05)。A组大鼠心脏组织结构无明显病理变化;B组大鼠心肌细胞边界模糊,可见大量炎性细胞浸润和坏死区域;D_1组、D_2组、D_3组大鼠心肌炎性细胞浸润数量减少,细胞结构及边界较B组明显好转。结论金丝桃苷对脓毒症模型大鼠的心肌损伤具有一定改善作用,其作用机制可能与金丝桃苷通过诱导HIF-1α/HO-1信号通路,激活脓毒症大鼠HIF-1α和HO-1蛋白的表达有关。Objective To investigate the improvement effect of hyperoside on myocardial cells of septic rats through hypoxia-inducible factor-1α/heme oxygenase-1(HIF-1α/HO-1)signaling pathway.Methods Totally 120 SD rats were randomly divided into normal control group(group A,equal volume of normal saline),model group(group B,equal volume of normal saline),positive drug control group(group C,10 mg/kg of dexamethasone)and hyperoside low-dose,medium-dose and high-dose groups(groups D1,D2 and D3,10,20 and 40 mg/kg of herb-drug),20 rats in each group.The rat models with sepsis were constructed by intraperitoneal injection of 0.3 mL/kg of 10%chloral hydrate.The rats in each group were intraperitoneally injected with the corresponding drugs for once and the killed 12 h after administration.The hemodynamic indexes of rats were detected.The levels of cardiac troponin I(cTnI)and brain natriuretic peptide(BNP)in serum,the levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the homogenization of cardiac tissue were detected by Enzyme linked immunosorbent assay(ELISA).The heart tissues were stained with hematoxylin eosin(HE)to observe the pathological changes of heart structure.The expression levels of HIF-1αand HO-1 protein in the hearts of rats were detected by immunohistochemical staining.Results Compared with those in group A,the left ventricular systolic pressure(LVSP),maximum increase rate of left ventricular pressure(+dp/dtmax),maximum decrease rate of left ventricular pressure(-dp/dtmax),levels of HIF-1αand HO-1 in group B were significantly decreased,while the left ventricular end diastolic pressure(LVEDP),cTnI,BNP,TNF-αand IL-1βin group B were significantly increased(P<0.05).Compared with those in group B,the LVSP,+dp/dtmax,-dp/dtmax,the levels of HIF-1αand HO-1 in groups C,D1,D2 and D3 were significantly increased,while the LVEDP,the levels of cTnI,BNP,TNF-αand IL-1βin groups C,D1,D2 and D3 were significantly decreased with a dose-dependent manner(P<0.05).Compared with those in group C,the LVSP,+dp

关 键 词：金丝桃苷 缺氧诱导因子-1α/血红素加氧酶-1信号通路 脓毒症 心肌损伤 作用机制 大鼠 

分 类 号：R965[医药卫生—药理学] R972[医药卫生—药学]