穿心莲酸对高脂饲料喂养C57BL/6及NLRP3基因敲除小鼠脂质及炎症水平的影响  

Effects of Andrographolic Acid on Levels of Lipids and Inflammation in C57BL/6 and NLRP3 Knockout Mice with High Fat Diet

作　　者：黄雪君 李钰婷 蔡大可 赖亦静 彭莎 胡子旋 甘海宁 陈玉兴 HUANG Xuejun;LI Yuting;CAI Dake;LAI Yijing;PENG Sha;HU Zixuan;GAN Haining;CHEN Yuxing(Guangdong Second Traditional Chinese Medicine Hospital,Guangdong Province Engineering Technology Research Institute of Chinese Medicine,Guangzhou,Guangdong 510095,China;Guangdong Provincial Key Lab of Research and Development in Traditional Chinese Medicine,Guangzhou,Guangdong 510095,China;Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510405,China)

机构地区：[1]广东省第二中医院广东省中医药工程技术研究院,广东广州510095 [2]广东省中医药研究开发重点实验室,广东广州510095 [3]广州中医药大学,广东广州510405

出　　处：《今日药学》2022年第1期35-39,共5页Pharmacy Today

基　　金：广东省医学科学技术研究基金(A2019308)。

摘　　要：目的研究穿心莲酸对高脂饲料喂养C57BL/6及NLRP3基因敲除小鼠脂质及炎症水平及其相关蛋白的影响。方法将18只C57BL/6小鼠和18只NLRP3基因敲除小鼠分别随机分为3组,每组6只,雌雄各半。分别为对照组(Control)、模型组(HFD)、穿心莲酸(ANDA,12.5 mg·kg^(-1))组。对照组小鼠给予维持饲料,其余小鼠每笼每天给予20 g高脂饲料喂养(high fat diet,HFD),连续8周。第5周起,ANDA组连续灌胃给药4周,其他组小鼠灌胃给予蒸馏水,每天1次。收集血样及肝脏,测定血清中TC、TG、HDL-c、LDL-c及IL-1β水平;Western Blot测定肝脏中caspase-1、IL-1β、CYP7A1及LXRα的蛋白表达水平。结果给予高脂饲料喂养后,WT小鼠和NLRP3-/-小鼠血清TC、TG、LDL-c水平均较对照组显著升高、HDL-c水平显著下降(P<0.01);与对应模型组相比较,穿心莲酸均能降低高脂饲料喂养的WT小鼠和NLRP3-/-模型小鼠血清TC、TG、LDL-C含量,提高HDL-c含量(P<0.01或P<0.05)。穿心莲酸明显下调高脂饲料喂养WT小鼠血清IL-1β的含量(P<0.01),对NLRP3-/-模型小鼠作用未见显著差异。穿心莲酸能下调高脂饲料喂养WT小鼠蛋白caspase-1、IL-1β的肝脏表达(P<0.01),对NLRP3-/-模型小鼠未见显著差异。穿心莲酸仅调控NLRP3-/-模型小鼠的肝脏CYP7A1蛋白表达(P<0.01),对WT模型小鼠未见显著差异。穿心莲酸对WT和NLRP3-/-模型小鼠肝脏LXRα蛋白表达均无显著作用。结论穿心莲酸具有一定调控血脂和抗炎作用,NLRP3基因敲除后穿心莲酸仍具有改善高脂饲料所致的血脂变化作用,增强了对肝CYP7A1蛋白表达的作用,但对下调caspase-1、IL-1β的炎症蛋白表达作用显著弱化。穿心莲酸的抗炎作用机制可能与NLRP3炎症小体通路相关。OBJECTIVE To study the effects of andrographolic acid on the levels of lipid and inflammatory and related proteins in C57BL/6 and NLRP3 knockout mice with high fat diet(HFD).METHODS 18 C57BL/6 mice and 18 NLRP3 knockout mice were randomly divided into 3 groups,each with 6 mice and had half male and half female.They are the control group(Control),model group(HFD),and andrographis acid(ANDA,12.5 mg·kg^(-1)) group.The mice in the Control group were given maintenance feed,and the remaining mice were fed with 20 g high fat diet(HFD) per cage per day for 8 weeks.From the 5 th week,the ANDA group was given continuous intragastric administration for 4 weeks,and the mice in the other groups were given distilled water once a day by intragastric administration.Blood and liver samples were collected and the levels of TC,TG,HDL-C,LDL-C and 1 L-1β in serum were determined.The protein expression levels of caspase-1,lL-1β,CYP7A1 and LXRα in liver were determined by Western Blot.RESULTS After feeding with HFD,serum levels of TC,TG and LDL-C in WT mice and NLRP3;mice were significantly increased and level of HDL-C were significantly decreased compared with control group(P<0.01).Compared with the corresponding model group,andrographolic acid could decrease the serum levels of TC,TG and LDL-C and increased level of HDL-C both in WT mice and NLRP3;mice(P<0.01 or P<0.05).Andrographolic acid could down-regulated the serum level of IL-1β in WT mice fed with HFD(P<0.01),but there was no significant difference in the effect in NLRP3;model mice.Moreover,the protein expression of caspase-1 and IL-1β in WT mice was down-regulated by andrographolic acid(P<0.01),but not in NLRP3;model mice.However,andrographolic acid could only regulated CYP7 A1 protein expression in the liver of NLRP3;model mice(P<0.01),but had no effect in WT model mice.Andrographolic acid had no significant effect on LXRα protein expression in the liver of WT and NLRP3;model mice.CONCLUSION Andrographolic acid has certain effects on lipid regulation and anti-inflamma

关 键 词：穿心莲酸 NLRP3 脂质 炎症 

分 类 号：R966[医药卫生—药理学]