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作 者:伏瑶 周继栋 桑晓宇 孙笛洋 赵启韬[1] 傅风华[2] FU Yao;ZHOU Ji-dong;SANG Xiao-yu;SUN Di-yang;ZHAO Qi-tao;FU Feng-hua(Shandong University of Traditional Chinese Medicine,Jinan 250355,China;School of Pharmaceutical Sciences,Yantai University,Yantai 264005,China)
机构地区:[1]山东中医药大学,济南250355 [2]烟台大学药学院,烟台264005
出 处:《中华中医药杂志》2020年第5期2613-2617,共5页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:国家自然科学基金项目(No.81173164,No.81573852);山东省重点研发计划公益类项目(No.2018GSF119009)
摘 要:目的:研究瓜蒌薤白半夏汤(GXB)对2型糖尿病合并急性心肌缺血(T2DM-AMI)大鼠造血干细胞(HSCs)的保护作用机制。方法:雄性Wistar大鼠随机分为对照组、模型组、GXB组。通过灌服高脂乳剂+腹腔注射链脲佐菌素制备T2DM大鼠模型;将T2DM造模成功的大鼠进行冠脉结扎制造T2DM-AMI模型。流式细胞仪检测各组大鼠外周血HSCs含量;PCR和Western Blot检测心肌磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、内皮型一氧化氮合酶(eNOS)mRNA和蛋白表达水平及被激活的程度(磷酸化/非磷酸化蛋白的比值)。结果:模型组大鼠外周血HSCs凋亡率显著高于对照组(P<0.01),而给予GXB后其凋亡率显著下调(P<0.05),且GXB组HSCs数量显著高于模型组(P<0.01)。与模型组比较,GXB组大鼠心肌组织中PI3K、Akt和eNOS蛋白表达及其磷酸化水平、mRNA相对表达量显著提高(P<0.05,P<0.01)。结论:GXB可能通过激活PI3K/Akt/eNOS信号通路发挥对T2DM-AMI模型大鼠HSCs的保护作用。Objective: To study the protective mechanism of Gualou Xiebai Banxia Decoction(GXB) on hematopoietic stem cells(HSCs) in type 2 diabetes mellitus rats with acute myocardial ischemia(T2 DM-AMI). Methods: Wistar male rats were randomly divided into the control group, model group and the GXB group. First, hyperlipidemia model rats were established by oral administration of high-fat emulsion, and then the model rats were intraperitoneally injected with streptozotocin to establish T2 DM model;finally, rats were taken ligation of left coronary artery to establish T2 DM-AMI model. Flow cytometer machine(FCM) was used to analysis the number and apoptosis rate of HSCs in their peripheral blood;Western Blot was performed to measure the PI3 K, Akt, eNOS, Phospho-PI3 K, Phospho-Akt and Phospho-eNOS protein expression in myocardial tissue;polymerase chain reaction(PCR) was used to detect the relative mRNA expressions of PI3 K, Akt and eNOS. Results: Compared with control group, the apoptotic rate of HSCs in the T2 DM-AMI group was significantly increased(P<0.01). After treatment with GXB, the cell apoptosis rate was significantly decreased(P<0.05), and the number of HSCs were significantly increased(P<0.01). Compared with the model group, the expression of p-PI3 K/PI3 K, p-Akt/Akt, p-eNOS/eNOS and the relative mRNA expressions of PI3 K, Akt and eNOS in GXB group were significantly increased(P<0.05, P<0.01). Conclusion: GXB may play a protective role on HSCs in T2 DM-AMI rats by activating PI3 K/Akt/eNOS signaling pathway.
关 键 词:瓜蒌薤白半夏汤 2型糖尿病 急性心肌缺血 造血干细胞 磷脂酰肌醇3-激酶 蛋白激酶B 内皮型一氧化氮合酶 机制
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