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基于Notch1信号通路研究通心络胶囊对糖尿病小鼠主动脉的保护作用

Effect of Tongxinluo Capsule in thoracic aorta of diabetic mice based on Notch1 signaling pathway
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摘要 目的观察通心络胶囊对糖尿病(DM)小鼠胸主动脉血管内皮细胞损伤的保护作用。方法构建DM小鼠模型并检测空腹血糖、血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)水平;ELISA法检测血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)和肿瘤坏死因子-α(TNF-α)等炎症因子的水平;HE染色和TUNEL法观察胸主动脉病理学特征及细胞凋亡情况;real-time PCR法及Western-Blot法检测胸主动脉Notch1、Bcl-2、Bax、Caspase-3 mRNA表达或蛋白表达。结果与对照组比较,模型组血糖、TG、TC、HDL及LDL均显著升高(P<0.01);且通心络组LDL较模型组显著降低(P<0.05)。与模型组比较通心络组血清IL-1β、IL-18和TNF-α显著降低(P<0.05)。TUNEL染色可见通心络组内皮细胞凋亡水平相比模型组有明显改善(P<0.05)。通心络组Bax、Caspase-3 mRNA及蛋白表达较模型组显著降低(P<0.05),Notch1、Bcl-2蛋白表达显著升高(P<0.05)。结论通心络胶囊可能是通过抑制炎症反应,并通过激活Notch1通路抑制细胞凋亡,改善血管内皮功能,从而发挥对糖尿病小鼠胸主动脉的保护作用。 Objective To investigate the protective effect of Tongxinluo Capsule on vascular endothelial cell damage of thoracic aorta in diabetic mice.Methods Male C57BL/6J mice were feeding high fat diet with intraperitoneal injection of streptozotocin to establish the diabetic mouse models.Fasting blood glucose of mice was detected.Lipids in total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were detected by automatic biochemical analyzer.Serum IL-1β,IL-18 and TNF-α levels were detected by ELISA.Thoracic aortic pathology by was characterized by hematoxylin and eosin(HE)staining.TUNEL method was used to detect endothelial cell apoptosis,real-time PCR orWestern blot was used to detect Notch1,Caspase-3,B-cell lymphoma-2(Bcl-2)and Bax mRNA/protein expressions.Results Compared with control group,the levels of blood glucose,TG,TC,HDL and LDL were higher in model group(P<0.01),and LDL was significantly lower in Tongxinluo group compared with model group(P<0.05).Compared with model group,levels of inflammatory cytokines IL-1β,IL-18 and TNF-α in Tongxinluo group were significantly decreased(P<0.05).The endothelial cells of the thoracic aorta of mice in model group were disordered under light microscope.The arrangement disorder of endothelial cells in Tongxinluo group was significantly reduced.TUNEL staining showed the apoptosis level has significant improvement in Tongxinluo group(P<0.05).The expression of Bax and Casepase-3 mRNA/protein in the thoracic aorta tissue of mice in Tongxinluo group was lower than that in model group,and the expression of Notch1,Bcl-2 mRNA/protein increased(all P<0.05).Conclusions Tongxinluo capsule may improve vascular endothelial function and preventor delay diabetic macrovascular disease by inhibiting inflammatory response,and inhibiting apoptosis and by Notch1 signaling pathway.
作者 赵静 张宝康 张若楠 张晓艳 张江华 李清 ZHAO Jing;ZHANG Bao-kang;ZHANG Ruo-nan;ZHANG Xiao-yan;ZHANG Jiang-hua;LI Qing(School of Integrated Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050031;Clinical College,Hebei Medical University,Shijiazhuang 050020;Hebei Provincial Hospital of TCM,Shijiazhuang 050013;Teaching and Research Department of TCMPharmacology,Hebei University of ChineseMedicine,Shijiazhuang 050200)
出处 《湖北中医药大学学报》 2023年第5期14-18,共5页 Journal of Hubei University of Chinese Medicine
基金 河北省中医药管理局项目2018年中医药类科研计划课题(项目编号:2018114) 河北医科大学临床学院2022年大学生创新性实验计划项目(项目编号:S202213415010S)。
关键词 糖尿病 通心络胶囊 胸主动脉 Notch1通路 细胞凋亡 Diabetes mellitus Tongxinluo Capsule Thoracic aorta Notch1 Cell apoptosis
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