摘要
目的探究调脂消斑合剂对高脂饮食诱导的大鼠动脉粥样硬化模型的干预作用,并初步评估长链非编码RNA(LincRNA)在该过程中表达水平的变化。方法采用高脂饮食诱导SD大鼠建立动脉粥样硬化模型。于造模后4周取动脉粥样硬化大鼠胸主动脉组织进行苏木精-伊红(HE)染色,系统评估不同剂量调脂消斑合剂的抗动脉粥样硬化效应。使用生化试剂盒检测血脂水平及肝肾功能相关指标,评估调脂消斑合剂对上述参数的影响;采用酶联免疫吸附法(ELISA)检测调脂消斑合剂干预后的血清炎症标志物;通过TUNEL染色法和Western blot法检测调脂消斑合剂对胸主动脉组织的促凋亡效应;使用qPCR技术检测Linc-HC、MALAT1等RNA分子的表达水平。结果经高剂量调脂消斑合剂干预后,动脉粥样硬化模型大鼠的血脂谱显示总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平显著降低(P<0.05,P<0.01),而高密度脂蛋白胆固醇(HDL-C)表达呈现升高趋势。在肝肾功能指标方面,天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血尿素氮(BUN)及肌酐(Cr)等血清标志物水平均显著下调(P<0.05,P<0.01)。促炎因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)和基质金属蛋白酶9(MMP-9)水平降低(P<0.01),而抗炎因子白细胞介素-10(IL-10)水平升高(P<0.01)。胸主动脉组织中凋亡相关因子NLRP3、ASC、Cleaved Caspase-1、Cleaved IL-1β、Puma、Bax、Noxa和MDM2的表达水平显著下调(P<0.05,P<0.01)。经调脂消斑合剂干预后,Linc-HC的mRNA水平显著降低(P<0.01),而MALAT1的mRNA表达显著上调(P<0.05,P<0.01)。结论调脂消斑合剂可能通过抑制Linc-HC的表达,同时上调MALAT1的表达,从而减少动脉粥样硬化斑块的形成,改善血脂异常及肝肾功能,缓解炎症反应并抑制细胞凋亡。
OBJECTIVE To explore the ameliorative effect of Tiaozhi Xiaoban Mixture on atherosclerosis and the potential role of long non-coding RNA(Linc RNA)in anti-atherosclerosis.METHODS A model of atherosclerosis was established in SD rats subjected to a high-fat diet.At 4 weeks post-modeling,thoracic aortic tissues from atherosclerotic rats were collected for hematoxylin-eosin(HE)staining to systematically evaluate the anti-atherosclerotic effects of Tiaozhi Xiaoban Mixture at different doses.Biochemical kits were utilized to assess relevant indices related to blood lipid levels as well as liver and kidney function,thereby evaluating the impact of Tiaozhi Xiaoban Mixture on these parameters.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum inflammation markers influenced by Tiaozhi Xiaoban Mixture.Additionally,TUNEL staining and Western blot analysis were conducted to examine the apoptotic effects of Tiaozhi Xiaoban Mixture on thoracic aorta tissue.Finally,qPCR was used to detect the expression levels of Linc-HC,MALAT1,etc.,in order to evaluate how Tiaozhi Xiaoban Mixture affecting these specific RNA molecules.RESULTS Following treatment with Tiaozhi Xiaoban Mixture,the blood lipid profiles indicated that total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were significantly down-regulated(P<0.05,P<0.01),while high-density lipoprotein cholesterol(HDL-C)levels were up-regulated in the atherosclerotic rats.Moreover,serum levels of liver and kidney function markers such as aspartate aminotransferase(AST),alanine aminotransferase(ALT),blood urea nitrogen(BUN),and creatinine(Cr)exhibited down-regulation(P<0.05,P<0.01).Additionally,pro-inflammatory factors including interleukin-6(IL-6),interleukin-1 beta(IL-1β),tumor necrosis factor-alpha(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and matrix metallopeptidase 9(MMP-9)were also reduced(P<0.01),whereas the anti-inflammatory factor interleukin-10(IL-10)was found to be elevated(P<0.01).Furthermore,after oral administration of Tiaozhi Xiaoban Mixture,expression levels of apoptosis-related factors NLRP3,ASC,Cleaved Caspase-1,Cleaved IL-1β,Puma,Bax,Noxa,and MDM2 in thoracic aorta tissues from the atherosclerotic rats showed significant down-regulation(P<0.05,P<0.01).Notably,following treatment with Tiaozhi Xiaoban Mixture,mRNA levels of Linc-HC decreased while mRNA expression of MALAT1 increased(P<0.05,P<0.01).CONCLUSION Tiaozhi Xiaoban Mixture may inhibit the expression of Linc-HC and up-regulate the expression of MALAT1 to reduce the formation of atherosclerotic plaque,improve abnormal blood lipids and liver and kidney function,alleviate inflammation and inhibit apoptosis.
作者
刘孟
章丹宁
曾峻楠
卢磊
梁田
徐颖
陈彤
赵欣
张寒梅
卞勇
王忠良
LIU Meng;ZHANG Danning;ZENG Junnan;LU Lei;LIANG Tian;XU Ying;CHEN Tong;ZHAO Xin;ZHANG Hanmei;BIAN Yong;WANG Zhongliang(Xuzhou Hospital of Chinese Medicine,Xuzhou Hospital Affiliated to Nanjing University of Chinese Medicine,Xuzhou 221000,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;School of Acupuncture-Moxibustion and Tuina of Nanjing University of Chinese Medicine,School of Health Preservation and Rehabilitation,Nanjing University of Chinese Medicine,Nanjing 210023,China;Laboratory Animal Center,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《南京中医药大学学报》
北大核心
2025年第9期1178-1188,共11页
Journal of Nanjing University of Traditional Chinese Medicine
基金
徐州市医学领军人才培养项目(XWRCHT20210021)
第五批全国中医临床优秀人才研修项目(532177)。
