葫芦巴碱结合有氧运动对高脂血症大鼠降脂作用及PCSK9/LDLR通路的影响  

Effects of trigonelline combined with aerobic exercise on lipid lowering and PCSK9/LDLR pathway in hyperlipidemia rats

作　　者：姜海斌[1] 蒋锐[2] 杨丽洁[1] JIANG Hai-bin;JIANG Rui;YANG Li-jie(Internal Medicine Teaching and Research Section,Changde Vocational and Technical College,Changde 415000,Hunan Province,China;Diagnostic Teaching and Research Section,Changde Vocational and Technical College,Changde 415000,Hunan Province,China)

机构地区：[1]常德职业技术学院内科教研室,湖南常德415000 [2]常德职业技术学院诊断教研室,湖南常德415000

出　　处：《中国临床药理学杂志》2024年第12期1794-1798,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 探讨葫芦巴碱联合有氧运动对高脂血症大鼠的影响及作用机制。方法 将SD大鼠随机分为对照组(正常饲料喂养)、模型组(高脂饲料喂养建立高脂血症大鼠模型)、低剂量实验组、高剂量实验组(高脂饲料+15、 45 mg·kg^(-1)的葫芦巴碱)、联合组(高脂饲料+45 mg·kg^(-1)的葫芦巴碱+有氧运动),每组11只大鼠。用全自动生化分析仪检测血清脂质代谢相关指标;用酶联免疫吸附试验法检测血清6酮前列腺素F1a (6-keto-PGF1a)水平及肝组织谷草转氨酶(GOT)水平;用实时荧光定量聚合酶链反应法检测肝组织白细胞介素-1β(IL-1β) mRNA水平;用蛋白质印迹法检测肝组织肝前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(PCSK9)、低密度脂蛋白受体(LDLR)蛋白相对表达水平。结果 对照组、模型组、低剂量实验组、高剂量实验组、联合组大鼠血清总胆固醇(TC)水平分别为(1.81±0.10)、(6.68±0.77)、(5.10±0.44)、(3.57±0.47)和(2.40±0.35) mmol·L^(-1),6-keto-PGF1a水平分别为(841.47±86.74)、(536.03±36.50)、(664.06±52.44)、(759.19±52.30)和(824.45±67.62) pg·mL^(-1),GOT水平分别为(11.95±0.88)、(18.20±1.81)、(15.05±1.10)、(13.32±0.98)和(12.47±0.83) U·L^(-1),IL-1β mRNA表达水平分别为1.00±0.09、2.21±0.17、1.57±0.10、1.26±0.16和1.14±0.09,PCSK9蛋白相对表达水平分别为0.39±0.07、0.88±0.08、0.71±0.08、0.60±0.04和0.52±0.07,LDLR蛋白相对表达水平分别为1.12±0.13、0.52±0.07、0.74±0.11、0.84±0.08和0.96±0.11。模型组上述指标与对照组比较,低、高剂量实验组上述指标与模型组比较,联合组上述指标与高剂量实验组比较,在统计学上差异均有统计学意义(均P<0.05)。结论 葫芦巴碱联合有氧运动可能通过抑制PCSK9表达,并上调LDLR表达改善脂代谢,从而对高脂血症大鼠发挥降脂作用。Objective To investigate the effects of trigonelline combined with aerobic exercise on hyperlipidemia rats and its mechanism.Methods SD rats were randomly divided into control group(normal diet),model group(hyperlipidemia rat model was established by feeding high fat diet),experimental-L,-H groups(high fat diet+15,45 mg·kg^(-1) trigonelline) and combine group(high fat diet+45 mg·kg^(-1)trigonelline+aerobic exercise).Each group had 11 rats.Serum lipid metabolism related indexes were detected by automatic biochemical analyzer.Serum levels of 6 ketone prostaglandin F1a(6-keto-PGF1a);the levels of glutamic oxaloacetic transaminase(GOT) in liver tissue were detected by enzyme—linked immunosorbent assay;the mRNA levels of interleukin-1β(IL-1β) in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR);Western blot assay was used to detect the expression of proprotein convertase subtilin/kexin 9 type(PCSK9) and low density lipoprotein receptor(LDLR) protein in liver tissue.Results The serum TC levels in control group,model group,experimental-L group,experimental-H group and combine group were(1.81±0.10),(6.68±0.77),(5.10±0.44),(3.57±0.47) and(2.40±0.35) mmol·L^(-1);the levels of 6-keto-PGF1a were(841.47±86.74),(536.03±36.50),(664.06±52.44),(759.19±52.30) and(824.45±67.62) pg · mL^(-1);GOT levels were(11.95±0.88),(18.20±1.81),(15.05±1.10),(13.32±0.98) and(12.47±0.83) U·L^(-1);IL-1β mRNA expression levels were 1.00±0.09,2.21±0.17,1.57±0.10,1.26±0.16 and 1.14±0.09;the expression of PCSK9 protein were0.39±0.07,0.88±0.08,0.71±0.08,0.60±0.04 and 0.52±0.07;LDLR protein levels were 1.12±0.13,0.52±0.07,0.74±0.11,0.84±0.08 and 0.96±0.11,respectively.Model group was compared with the control group,experimental-L group and experimental-H group were compared with model group respectively,combine group was compared with the experimental-H group,the differences of the above indexes were statistically significant(all P <0.05).Conclusion Trigonelline co

关 键 词：葫芦巴碱 有氧运动 高脂血症 肝前蛋白转化酶枯草杆菌蛋白酶/kexin 9型/低密度脂蛋白受体通路 脂代谢 

分 类 号：R28[医药卫生—中药学]