机构地区:[1]联勤保障部队临潼康复疗养中心,西安710699 [2]甘肃省中心医院,兰州730050 [3]联勤保障部队第九四〇医院,兰州730050
出 处:《中西医结合心脑血管病杂志》2024年第20期3689-3696,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基 金:甘肃省科技计划项目(创新基地和人才项目)(No.21JR7RA013)。
摘 要:目的:探究原儿茶酸(PCA)对高脂血症大鼠血脂代谢及丝裂原活化蛋白激酶(MAPK)通路的影响。方法:将SD大鼠按照随机数表法分为对照组、模型组、阳性药物对照组(阳性组)、低PCA组和高PCA组,每组10只。对照组大鼠给予基础对照饲料喂养,模型组、阳性组、低PCA组和高PCA组大鼠均给予45%高脂饲料喂养造模。建模第3周开始,阳性组大鼠每日给予阿伐他汀钙溶剂(5 mg/kg)灌胃;低PCA组和高PCA组大鼠每日分别给予100 mg/kg和200 mg/kg的PCA溶剂灌胃;对照组和模型组大鼠每日分别灌胃等量的生理盐水,各组大鼠均持续给药4周。给药过程中,每周分别测量各组大鼠的体质量。给药结束时,各组大鼠采用腹腔1%戊巴比妥钠麻醉,开胸腔后分离大鼠肝脏组织和采集腹主动脉血,分离收集血清。通过全自动生化分析仪检测大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平。采用试剂盒检测各组大鼠肝脏和血清中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平,检测血清白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)水平。采用逆转录-聚合酶链式反应(RT-PCR)检测各组大鼠肝脏组织中胆固醇调节元件结合蛋白2(SREBP2)和3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGCR)基因的相对表达量。采用蛋白质免疫印迹法(Western Blot)检测各组大鼠肝脏组织中SREBP2、HMGCR、p38MAPK、磷酸化p38MAPK(p-p38MAPK)、胞外调节蛋白激酶(ERK)、磷酸化ERK(p-ERK)、Jun氨基末端激酶(JNK)和磷酸化JNK(p-JNK)表达水平。采用苏木素-伊红(HE)染色检测各组大鼠肝脏组织的病变情况。结果:与对照组比较,模型组、阳性组、低PCA组和高PCA组大鼠肝脏指数、TC、TG、LDL-C、MDA、IL-1β、IL-6和TNF-α水平均升高(P<0.05),HDL-C、SOD和GSH-Px水平均降低(P<0.05);与模型组比较,阳性组、低PCA组和高Objective:To explore the effects of protocatechuic acid on lipid metabolism and mitogen-activated protein kinase(MAPK)pathway in hyperlipidemia rats.Method:SD rats were randomly divided into control group,high fat model group,positive drug control group(positive group),low dose protocatechuic acid group(low PCA group)and high dose protocatechuic acid group(high PCA group)according to random number table,with 10 rats in each group.The rats in the control group were fed a basal control diet,while the rats in the model group,positive group,low PCA group,and high PCA group were fed a 45%high-fat diet for modeling.At the 3rd week of modeling,rats in the positive group were administered daily with atorvastatin calcium solvent(5 mg/kg).The rats in the low PCA group and high PCA group were given PCA solvent 100 mg/kg and 200 mg/kg daily,respectively.Rats in the control group and model group were administered the same volume of normal saline intragastrically every day,and all rats in each group received continuous medication for 4 weeks.The body weight of each group was measured weekly.At the end of the administration,1%sodium pentobarbital was injected into the abdominal cavity for anesthetization.The liver tissue and abdominal aortic blood were then separated,and serum was collected after thoracotomy.The contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoproteincholesterol(HDL-C)in serum of rats were detected by automatic biochemical analyzer.The contents of malonaldehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in liver and serum of rats in each group were detected by the kit,and the levels of interleukin(IL)-1β,IL-6 and TNF-αin serum were detected by the kit.The relative expression levels of cholesterol regulatory element binding protein 2(SREBP2)and 3-hy-droxy-3-methylglutaryl-coenzyme areductase(HMGCR)genes in liver tissues of each group were detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression level
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