基于NLRP3炎症小体探讨肝龙胶囊联合去脂软肝方用药对NASH大鼠的防治作用  

Preventive effects of Ganlong Capsule combined with Quzhi Ruangan Decoction in non-alcoholic steatohepatitis rats base on the NLRP3 inflammasome

作　　者：张素妍 夏恩蕊 周青丽 张顺贞 ZHANG Su-yan;XIA En-rui;ZHOU Qing-li;ZHANG Shun-zhen(Yunnan University of Chinese Medicine,Kunming 650000,China)

机构地区：[1]云南中医药大学,昆明650000

出　　处：《中华中医药杂志》2022年第1期450-454,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：云南省科技厅中医联合专项[No.2018FF001(-042)]。

摘　　要：目的:探讨肝龙胶囊联合去脂软肝方用药对高脂饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠NLRP3炎症小体的影响。方法:40只SD雄性大鼠随机分为正常组、模型组、辛伐他汀组、肝龙胶囊组、联合用药组,每组8只。正常组给予普通饲料,其余组给予高脂饲料建立NASH模型。14周后取材,测定血清生化指标(ALT、AST、TC、TG、HDL-C、LDL-C)、肝脏炎症因子(IL-1β、IL-18)水平,采用HE染色和油红O染色的方法观察肝脏组织病理学变化,RT-PCR、免疫组化检测肝组织NLRP3炎症小体mRNA和蛋白水平。结果:与正常组比较,模型组大鼠肝指数及ALT、TC、LDL-C、IL-1β、IL-18、NLRP3炎症小体mRNA和蛋白水平均显著升高(P<0.05,P<0.01),肝组织出现显著的细胞脂肪变性及空泡样变;与模型组比较,各药物组肝指数及ALT、TC、LDL-C、IL-1β、IL-18、NLRP3炎症小体mRNA和蛋白水平均显著降低(P<0.05,P<0.01),脂肪变性和炎症反应减轻;与辛伐他汀组比较,肝龙胶囊组LDL-C水平显著降低(P<0.05),联合用药组TC、LDL-C水平均显著降低(P<0.05,P<0.01);与肝龙胶囊组比较,联合用药组TC、IL-18、NLRP3炎症小体蛋白水平均显著降低(P<0.05,P<0.01),脂肪变性和炎症反应减轻。结论:肝龙胶囊对高脂饮食诱导的NASH大鼠具有防治作用,联合去脂软肝方用药效果更显著,其作用机制可能与下调NLRP3炎症小体的表达有关。Objective:To investigate the effects of Ganlong Capsule combined with Quzhi Ruangan Decoction on NLRP3 inflammasome of rats with non-alcoholic steatohepatitis(NASH)induced by high-fat diet.Methods:A total of 40 male SD rats were randomly divided into normal group,model group,Simvastatin group,Ganlong Capsule group and combined treatment group,8 rats in each group.The rats in the normal group were given normal diet,and those in the other groups were given highfat diet to establish a model of NASH.Samples were collected 14 weeks later,serum biochemical index(ALT,AST,TC,TG,HDL-C,LDL-C),inflammatory factor(IL-1β,IL-18)of liver were observed,HE staining and oil red O staining were performed to observe the liver histopathological changes,NLRP3 inflammasome mRNA and protein expression levels in liver tissue were detected by PT-PCR and immunohistochemistry,respectively.Results:Compared with the normal group,the model group showed fatty change of liver tissue and had significant increases in the liver index,and the levels of ALT,TC,LDL-C,IL-1β,IL-18(P<0.05,P<0.01),as well as NLRP3 inflammasome.Liver tissue showed significant hepatocyte steatosis and vacuolar degeneration.Compared with the model group,treatment groups demonstrated significant decrease in ALT,TC,LDL-C,IL-1β,IL-18,and the mRNA and protein expression of NLRP3 inflammasome(P<0.05,P<0.01),as well as obvious reduction in liver fatty degeneration and inflammatory reactions.Compared with the Simvastatin group,Ganlong Capsule group had significant reductions in the level of LDL-C(P<0.05),combined treatment group had significant reductions in the levels of TC and LDL-C(P<0.05,P<0.01).Compared with the Ganlong Capsule group,combined treatment group had significant reductions in the levels of TC,IL-18 and the protein expression of NLRP3(P<0.05,P<0.01),hepatocyte steatosis and vacuolar degeneration improved significantly.Conclusion:Ganlong Capsule has a preventive and therapeutic effect on NASH rats induced by high-fat diet,the combined use of Ganlong Capsule and Qu

关 键 词：非酒精性脂肪性肝炎 肝龙胶囊 去脂软肝方 NLRP3炎症小体 联合用药 动物模型 防治作用 机制 

分 类 号：R285.5[医药卫生—中药学]